Compositions and methods for treating bile acid malabsorption

Abstract

Pharmaceutical compositions comprising bile acid sequestrants, their use in treating bile acid malabsorption, and associated conditions such as bile acid diarrhea and colitis are described herein. Methods for treating bile acid malabsorption and associated conditions are also described.

Description

Compositions and methods for treating bile acid malabsorptionField of the Invention

[0001] The present invention relates to pharmaceutical compositions comprising bile acid sequestrants, and their use in treating bile acid malabsorption, and associated conditions such as bile acid diarrhea and bile acid colitis, as well as methods for treating bile acid malabsorption and associated conditions.Background

[0002] Bile acids (also called bile salts) are the main functional components of bile, which is produced in the liver and stored in the gallbladder. After a meal, this stored bile is secreted into the duodenum, where it exerts its functional role in digestion. Bile acids are natural surfactants, which solubilize lipids and lipophilic substances through formation of micelles.

[0003] Bile acids are endogenous surfactants synthetized in the liver by the cytochrome P450-mediated oxidation of cholesterol and play a key role in the absorption of dietary fats from the small intestine. They are conjugated with the amino acids taurine or glycine, or with a sulfate or a glucuronide, and are then transported across canalicular membrane of the hepatocytes into the bile and stored in the gallbladder, from which they are secreted into the duodenum to solubilize fats contained into the diet.

[0004] After each meal, bile acids are released into duodenum, the first tract of the small intestine, where they exert their role as physiological detergents molecules, facilitating the absorption of lipids and liposoluble nutrients, including liposoluble vitamins, from the small intestine. Bile acids are ionized in the lumen of the small intestine, and the ionization increases their water solubility and renders bile acids impermeable to cell membranes, allowing them to reach the critical micellar concentration, which is the concentration above which micelles are formed. The micelles are needed in the small intestine for digestion and absorption of lipids, and lipophilic substances such as some vitamins.

[0005] Once the bile acids have exerted their role in the duodenum and jejunum, about 95% of the secreted amount is reabsorbed by active transport in the ileum and delivered back to the liver via the portal vein. This process, known as enterohepatic circulation of bile acid, may involve hepatic conjugation and intestinal deconjugation. As an effect, only about 5% of the secreted amount is lost into the feces. Daily loss of bile acids is compensated by de novo synthesis in the liver and thus, a constant bile acid pool is maintained. The intestinal bile acid uptake is mainly mediated by the apical sodium dependent bile salt transporter (ASBT). (Li T. et al., Regulation of Bile Acid and Cholesterol Metabolism by PPARs. Hindawi Publishing Corporation, Vol 2009, Article ID 501739).

[0006] In humans, the bile acid pool consists of primary bile acids and secondary bile acids. The primary bile acids are synthesized from cholesterol exclusively in the liver through two pathways, the classic pathway (accounting for about 90% of bile acid synthesis) and the alternative pathway (accounting for about the remaining 10%). The secondary bile acids are synthesized from primary bile acids by bacterial enzymes of the natural microbiota resident into the intestine. (Li T. et al., Regulation of Bile Acid and Cholesterol Metabolism by PPARs. Hindawi Publishing Corporation, Vol 2009, Article ID 501739).

[0007] Enterohepatic circulation of bile acids is an efficient process capable of cycling these important compounds between the liver and intestine multiple times during the day.

[0008] Abnormal bile acids homeostasis and lack of, or impaired reabsorption into the bloodstream, can exacerbate several disorders including Crohn’s disease (CD), hepatic microvascular dysplasia, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), colonic cancer, cholestasis, insufficient control of blood glucose and cardiovascular disease. Subsequently, lack of, or impaired reabsorption of bile acids in the ileum and the enterohepatic bile acid circulation resulting in watery diarrhea. Bile acids in the large bowel cause abnormally high levels of water and salts to get into the large bowel from the bloodstream, causing watery diarrhea.

[0009] Bile acid malabsorption (BAM) is a defect in this enterohepatic circulation of bile acids, whereby increased proportions of the secreted bile acids are not reabsorbed in the ileum and reach the colon consequently. Bile acids in the colon activate increase fluid secretion, increase colonic motility and thereby decrease colonic transit time. Overall, this generates a chronic watery diarrhea (also known as Bile Acid Diarrhea, (BAD)), accompanied by further symptoms such as bloating, pain, faecal urgency and faecal incontinence. It is currently estimated that about 1% of the population has Bile Acid Diarrhea, and that about 30% of all irritable bowel syndrome with diarrhea (IBS-D) cases are due to Bile Acid Malabsorption. Bile Acid Malabsorption has also been associated with other diseases and conditions, such as microscopic colitis, Crohn’s disease, HIV-related enteritis, persistent diarrhea following bacterial infection and exocrine pancreatic insufficiency.

[0010] Currently, Bile Acid Diarrhea is subdivided in 3 main types: type 1 results from terminal ileal resection / bypass or disease (for example: Crohn’s disease or ileal resection), which results in failure of enterohepatic recycling of bile acids, and excess amounts entering the colon. Type 2 often referred to as primary (or idiopathic) bile acid diarrhea, is the most common cause of bile acid malabsorption and may account for at least 30% of individuals who would otherwise be labeled as having IBS-D or functional diarrhea. Despite much investigation, the etiology and pathogenesis of type 2 Bile Acid Diarrhea is poorly understood. Type 3 includes causes not included with types 1 and 2 that may interfere with normal bile acid cycling, small intestinal motility, or composition of ileal contents: for example, small intestine bacterial overgrowth, chronicpancreatitis, celiac disease, etc. (DIBaise, Nutrition Issues in Practical Gastroenterology, Series #198, Practical Gastroenterology 2020). There is also a type 4, which is the excess of bile acid production as side effect of therapy with metformin.

[0011] To treat the diarrheic effects generated by the excess of bile acids in the colon, bile acid sequestrants substances are commonly used in clinical practice, although these products have no approval for such use and are approved for lowering the cholesterol in the blood. Cholestyramine, colestipol, and colesevelam are the three main bile acid sequestrants currently available in the US and European markets.

[0012] Currently used sequestrant substances are available as granules for suspension or capsule shape tablets that require a very high amount of active ingredient with several administrations per day. This creates issues with patient compliance.

[0013] First-generation bile acid sequestrants (or resins) are cholestyramine or colestipol are available as powders or granules. However, patients are often intolerant to those sequestrants, given its side effects such as nausea, bloating, and constipation. Moreover, an efficacious treatment of BAD requires the administration of very high doses of these bile acid sequestrants: cholestyramine up to 36 g per day; colestipol up to 30 g per day (Wilcox et al., Aliment Pharmacol Ther 2014; 39: 923-939). These very high doses of cholestyramine or colestipol are not tolerated by many patients, because these compounds are in form of powders and have a very low palatability. Discontinuation rates have been reported to range from 34% to 60%. Colesevelam (and salts thereof, e.g. hydrochloride salt) is a second-generation bile acid sequestrant, which is commercially available as immediate release tablets or granules. Even though the recommended dose of colesevelam for treating BAD is reduced as compared to cholestyramine and colestipol, it remains high and corresponds to 6 or 7 tablets per day. Given the chronicity of the disease, there are patient compliance issues reported as well for colesevelam, because of the high number of tablets per day. When administered in the form of granules, colesevelam is known to generate a so called “sand effect” in the mouth that most patients find particularly unpleasant, and which discourages them from continuing their treatment. There is an immediate need for an improved formulation of bile acid sequestrants capable of increasing the patient’s compliance; in particular, there is an immediate need for a formulation of bile acid sequestrants in form of tablets, with a high drug content of active substance per dosage unit while maintaining the dimensions small enough to allow for easy administration.

[0014] Currently available bile acid sequestrant is released in the upper Gl tract. As such, the use of such compositions for treatment of BAM has several drawbacks, such as negative drug-drug interactions, decreased absorption of fat-soluble vitamins, and a negative impact on the absorption of other medications. Moreover, the available formulations of bile acid sequestrants have some adverse reactions (e.g., nausea, dyspepsia and bloating), which are due to their unspecific effect in the upper Gl tract.

[0015] W02021 / 163007 (Viscera) provides a colesevelam colon specific drug delivery system for use in the treatment of cholestasis and / or cholestatic pruritis. Described therein is an oral drug delivery system comprising: a) a core comprising a therapeutically effective amount of at least one active agent present in an amount of from about 35% to about 65% w / w of the core, and a drug release controlling component capable of providing release of the active agent primarily in a region selected from the group consisting of the lower gastrointestinal tract, the large intestine, the jejunum, the ileum, the cecum, the colon, the rectum, and combinations thereof, b) an outer coating encasing the core, and optionally a plasticizer, wherein after ingestion by a patient the active agent is released primarily in the region selected from the group consisting of the lower gastrointestinal tract, the large intestine, the jejunum, the ileum, the cecum, the colon, the rectum, and combinations thereof.

[0016] The recommended dose for colesevelam for treating bile acid malabsorption is high (3.75 g per day), which corresponds to around 6 tablets comprising 625 mg colesevelam hydrochloride per day. The tablets can be administered either in a single non-fractionated administration or in multiple fractionated administrations, e.g., six tablets once per day, or three tablets twice per day, or two tablets thrice per day. Given the chronicity of the disease, and the high number of tablets required per day, patient compliance issues often occur when treating with colesevelam.

[0017] The current commercially available formulations of bile acid sequestrants are characterized by immediate release in the stomach. The bile acid sequestrants therefore exert their pharmacological action starting in the duodenum: once the bile acids are released by the gallbladder in the duodenum, they are bound by the sequestrants and cannot exert their physiological digestive role of solubilization and absorption-enhancement of lipids and liposoluble vitamins. This leads to nutritional disorders and deficiencies of liposoluble vitamins.

[0018] Additionally, the effect on the bile acids in the upper Gl is suboptimal when the disease to be treated is caused by an excess of bile acids entering the colon; in other words, the currently available formulations do not target only the excess of bile acids entering the colon in a patient with bile acid malabsorption / bile acid diarrhea, but target the whole pool of bile acids released from the gallbladder and transiting the upper small intestine segments, i.e. the duodenum and jejunum.

[0019] Furthermore, bile acid sequestrants are non-specific, in that they bind a lot of different substances, preventing their absorption from the small intestine. Importantly, bile acid sequestrants are known to bind several drugs administered orally, a characteristic which has an impact on the systemic bioavailability of those drugs, because, once these are bound to the resin polymer chain, they are not absorbed and are excreted in the faeces. Most orally administered drugs are absorbed in the upper Gl tract, i.e. in the stomach, or in the duodenum or in the jejunum. The currently available formulations of bile acid sequestrants, which release the resin in thestomach, have a significant interaction with drugs absorbed in the upper Gl tract, which leads to the need of administering these drugs at least 4 hours prior to bile acid sequestrants, leading to difficulties for the physician to draw an effective treatment schedule for patients taking several concomitant medications.

[0020] Finally, the currently available formulations of bile acid sequestrants, although in general are regarded to as safe, have some adverse reactions (e.g., nausea, dyspepsia, bloating), which are due to their effect in, and transit throughout, the whole Gl tract, from the stomach to the colon.

[0021] There is therefore the need for new treatment options for bile acid malabsorption and bile acid diarrhea which overcomes the above highlighted limitations of the currently available treatments.SUMMARY

[0022] The present invention provides pharmaceutical compositions which resolve the above-mentioned drawbacks. The pharmaceutical compositions described herein are characterized by a high drug load, allowing for reduced number of administrations per day, and delivery of the active substance in the low intestinal districts to avoid unwanted interference with the natural role of the bile acids.

[0023] In one aspect, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof and optionally one or more of a diluent, a disintegrant, a glidant and a lubricant; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 66 wt% of the tablet core, such as at least about 70 wt% of the tablet core.

[0024] Thus, the total amount of colesevelam and / or pharmaceutically acceptable salts thereof in the unit dose pharmaceutical composition for oral administration accounts for at least 66 wt% of the tablet core, such as at least about 70 wt% of the tablet core. The total amount of colesevelam and or pharmaceutically acceptable salts thereof in the unit dose includes the amount of colesevelam and / or pharmaceutically acceptable salts thereof in the granulate component and in the non-granulate component.

[0025] The colesevelam and / or pharmaceutically acceptable salts thereof may be present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, optionally 30 to 50 wt% of the tablet core, optionally 35 to 45 wt% of the tablet core.

[0026] The colesevelam and / or pharmaceutically acceptable salts thereof may be present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core, optionally 30 to 50 wt% of the tablet core, optionally 35 to 45 wt% of the tablet core.

[0027] Together the amount of colesevelam and / or pharmaceutically acceptable salts thereof in the non-granulate component and the amount in the granulate component accounts for at least 66 wt% of the tablet core, such as at least about 70 wt% of the tablet core. For example, the amount of colesevelam and / or pharmaceutically acceptable salts thereof in the non-granulate component and the amount in the granulate component accounts for at least 66 wt% of the tablet core, such as an amount of from 66 wt% to 90 wt% of the tablet core, optionally in an amount of from 70 wt% to 90 wt% of the tablet core, optionally, in an amount of from 75 wt% to 90 wt% of the tablet core, such as from 76 wt% to 90 wt% of the tablet core, suitably 80 wt% to 90 wt% of the tablet core, such as from 81 wt% to 90 wt% of the tablet core, optionally, from 82 wt% to 90 wt% of the tablet core.

[0028] Suitably, colesevelam and / or pharmaceutically acceptable salts thereof is present in the unit dose pharmaceutical composition for oral administration in an amount of at least 70 wt%, or at least 75 wt%, or at least 76 wt% of the tablet core, suitably at least 80 wt% of the tablet core, more suitably at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core. For example, colesevelam and / or pharmaceutically acceptable salts thereof is present in the unit dose pharmaceutical composition for oral administration in an amount of 70 wt% to 90 wt% of the tablet core, or in an amount of 75 wt% to 90 wt% of the tablet core, or in an amount of 76 wt% to 90 wt% of the tablet core, suitably in an amount of 80 wt% to 90 wt% of the tablet core, more suitably 81 wt% to 90 wt% of the tablet core, optionally in an amount of from 82 wt% to 90 wt% of the tablet core.

[0029] The weight percentages of colesevelam or a pharmaceutically acceptable salt(s) thereof refers to the weight percent of anhydrous colesevelam or a pharmaceutically acceptable salt(s) thereof. For example, “at least 66 wt% colesevelam and / or pharmaceutically acceptable salt thereof” implies “at least 66 wt% anhydrous colesevelam and / or pharmaceutically acceptable salt thereof”. For example, “at least 66 wt% colesevelam hydrochloride” implies “at least 66 wt% anhydrous colesevelam hydrochloride”. Hydrated forms of colesevelam may also be used, however, the amounts employed are adjusted to compensate for the amount of water present i.e. when using hydrated forms of colesevelam, the amount of water / hydrate present in the hydrated colesevelam does not contribute to the weight percentage of colesevelam based on dry weight.

[0030] Suitably, hydrated forms of colesevelam or pharmaceutically acceptable salts thereof that may be used in the present invention comprise less than about 20 wt% water based on the total weight of the hydrated colesevelam or pharmaceutically acceptable salt thereof, preferably less than about 10 wt%, e.g. about 1 wt% , or about 2% wt%, or 3 wt%, or 4 wt%, or 5 wt%, or 6 wt%, or 7 wt%, or 8 wt%, or 9 wt%, water based on the total weight of the hydrated colesevelam or pharmaceutically acceptable salt thereof or any fractions of the above integers. When using hydrated forms of colesevelam, the amount of water present in the hydrated colesevelam (shall be compensated for, thus in order to achieve 0.9 X g of colesevelam (based on dry weight colesevelam), X g of a hydrated colesevelam comprising 10% water would be required.

[0031] Suitably, the colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of from 400 mg to 1250 mg in the tablet core, preferably in an amount of from 400 mg to 1200 mg in the tablet core, such as from 700 to 1200 mg in the tablet core, more preferably in an amount of from 850 mg to 1100 mg in the tablet core. Suitably, the colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of about 900 mg in the tablet core.

[0032] The unit dose may be formulated for delayed release, optionally for delayed release in the ileum. Optionally, the unit dose may be formulated for release starting and reaching 100% release in the ileum prior to entering the colon. The unit dose may be formulated for extended release, optionally for extended release starting in the ileum and continuing into the initial portion of the colon. The unit dose may be formulated for delayed / extended release, optionally for delayed release in the ileum and extended release continuing into the colon, e.g., continuing into the ascending colon.

[0033] Optionally, pharmaceutical composition is formulated for release starting and reaching 100% release in the ileum prior to entering the ascending colon.

[0034] Optionally, the pharmaceutical composition is formulated for release starting in the ileum and continuing into the colon, e.g., continuing into the ascending colon.

[0035] Optionally, the pharmaceutical composition is formulated for release starting in the ileum and continuing throughout the ascending colon.

[0036] Optionally, the pharmaceutical composition is formulated for release starting in the ileum and continuing throughout the ascending and transverse colon.

[0037] Optionally, the pharmaceutical composition is formulated for release starting in the ileum and continuing throughout the ascending and transverse colon and the descending colon.

[0038] Optionally, the pharmaceutical composition is formulated for release starting in the ileum and continuing throughout the ascending and transverse colon and the descending colon and sigmoid colon.

[0039] Optionally, the pharmaceutical composition is formulated for release starting in the ileum and continuing throughout the ascending and transverse colon and the descending colon and sigmoid colon and rectum.

[0040] Optionally, the non-granulate component of the unit dose pharmaceutical composition may also comprise a diluent.

[0041] The diluent (of the granulate component and / or non-granulate component) may be selected from one or more of polyols such as mannitol, lactose; sugars such as sucrose, dextrose, dextrates, sorbitol, fructose; inorganic salts such as dibasic and tribasic calcium phosphate, sodium chloride, starch, modified starch and derivatives thereof, cellulose, a cellulose derivative (i.e., cellulose derivatives such as, for example, methyl, ethyl, hydroxyethyl cellulose and similar), and kaolin. Preferably, the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative.

[0042] The diluent (of the granulate component and / or non-granulate component) may be present in an amount of from 5 to 20 wt% of the tablet core, such as from 6 to 18 wt% of the tablet core, optionally from 7 to 16 wt% of the tablet core, optionally from 10 to 15 wt% of the tablet core.

[0043] The binder may be selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, such as hydroxypropylcellulose, ethylcellulose, and hypromellose, a polymethacrylate, acacia gum and starch or modified starch. Preferably, the binder is polyvinyl pyrrolidone or polyvinyl alcohol.

[0044] The binder may be present in an amount of from 1 wt% to 5 wt% of the tablet core, optionally from 2 wt % to 4 wt% of the tablet core.

[0045] The composition may optionally include a disintegrant. The disintegrant may be selected from one or more of sodium carboxy methyl cellulose, such as cross-linked sodium carboxy methyl cellulose, crospovidone, bentonite, an algin (e.g., alginic acid or a salt thereof, such as sodium alginate), a gum, and modified starch, preferably, wherein the disintegrant is cross-linked sodium carboxy methyl cellulose or modified starch, more preferably wherein the disintegrant is cross-linked sodium carboxy methyl cellulose.

[0046] The disintegrant may be present in an amount of from 0.1 wt% to 7 wt% of the tablet core, optionally from 0.5 wt % to 5 wt%, such as from 1 to 2.5 wt% of the tablet core, optionally from 1 to 2 wt% of the tablet core.

[0047] Suitably, the disintegrant is present in the non-granulate component of the unit dose pharmaceutical composition.

[0048] The unit dose pharmaceutical composition may further comprise a glidant and / or lubricant.

[0049] Optionally, the tablet core comprises a glidant selected from the group comprising: talc, starch, magnesium oxide, silica (silicon dioxide), and a silicate, such as magnesium or calcium silicate. Preferably, the glidant is colloidal silicon dioxide, talc, or magnesium oxide.

[0050] Optionally, the tablet core comprises a glidant present in an amount of from 0.1 to 2 wt% of the tablet core, optionally the glidant is present in an amount of from 0.5 to 1 .5 wt% of the tablet core, optionally the glidant is present in an amount of from 0.5 to 1 wt% of the tablet core, further, optionally, the glidant is present in an amount of from 0.7 to 1.2 wt% of the tablet core.

[0051] Optionally, the tablet core comprises a lubricant selected from the group comprising: stearic acid and salts thereof (e.g., magnesium, calcium or zinc stearate), polyethylene glycol, fumaric acid and salts thereof, glyceryl behenate, glyceryl palmitostearate, wax, poloxamer, sodium benzoate, and any combination thereof. Preferably, the lubricant is stearic acid or a salt thereof, fumaric acid or a salt thereof, or polyethylene glycol.

[0052] Optionally, the tablet core comprises a lubricant present in an amount of from 0.1 to 2 wt% of the tablet core, optionally the lubricant is present in an amount of from 0.5 to 1 .5 wt% of the tablet core, optionally the lubricant is present in an amount of from 0.5 to 1 wt% of the tablet core, further optionally, the lubricant is present in an amount of from 0.7 to 1 .2 wt% of the tablet core.

[0053] Optionally, the unit dose pharmaceutical composition further comprises a subcoating between the tablet core and the gastro-resistant coating, wherein optionally, the subcoating comprises hydroxypropyl cellulose.

[0054] The gastro-resistant coating (film) covering the tablet core may contain a polymethacrylate, acrylic and / or methacrylic acids polymers or copolymers, or a cellulose derivative, such as cellulose acetophthalate. Optionally, the gastro-resistant coating can comprisemethacrylic acid / methyl methacrylate (1:1 ) copolymer (e.g., commercially known as EUDRAGIT L). Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacrylate (1 :2) copolymer (e.g., commercially known as EUDRAGIT S). Optionally, the gastro-protective coating comprises methacrylic acid-ethylacrylate (1:1) copolymer (e.g., commercially known as EUDRAGIT L30 D55). Optionally, the gastro-resistant coating contains polymethacrylate copolymer including, but not limited to, compounds known commercially as EUDRAGIT S (methacrylic acid-methyl methacrylate copolymer 1 :2), EUDRAGIT L (methacrylic acid- methyl methacrylate 1 :1 copolymer) and / or EUDRAGIT L30 D55 (methylacrylic acid-ethylacrylate 1: 1 copolymer), and / or mixtures thereof. The gastro-resistant coating may comprise a methacrylic acid - (meth)acrylate copolymer. Suitably, the gastro-resistant coating comprises methacrylic acid / methyl methacrylate copolymer.

[0055] Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacrylate (1: 1) copolymer (EUDRAGIT L).

[0056] Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacrylate (1:2) copolymer (EUDRAGIT S).

[0057] Suitably, the gastro-resistant coating comprises a mixture of methacrylic acid / methyl methacrylate (1 :1) copolymer and of methacrylic acid / methyl methacrylate (1:2) copolymer. Optionally, the mixture comprises a weight ratio of 0.5:1 to 3:1 of methacrylic acid / methyl methacrylate (1 :1) copolymer to methacrylic acid / methyl methacrylate (1:2). Optionally, the mixture comprises a weight ratio of 1 :1 to 3: 1 of methacrylic acid / methyl methacrylate (1 :1 ) copolymer to methacrylic acid / methyl methacrylate (1:2). Preferably, the mixture comprises a weight ratio of about 2: 1 of methacrylic acid / methyl methacrylate (1: 1) copolymer to methacrylic acid / methyl methacrylate (1:2).

[0058] Optionally, the gastro-resistant coating of the unit dose starts breaking or dissolving at or above a pH of 5, optionally, at or about a pH of 6, more preferably at or above a pH of 6.5, much more preferably at a pH of 6.8.

[0059] Optionally, the tablet core has a friability of less than about 1.0%, optionally, less than about 0.5%, preferably less than about 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7. For example, the tablet core may have a friability of 0.001 to 1 %, or from 0.01 to 0.5%, such as from 0.01 to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0060] Optionally, the tablet core has a hardness of greater than about 70 N, optionally, greater than about 80 N, optionally, greater than about 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Thetablet core may have a hardness in the range of from 70 N to 450 N, such as from 80 N to 400 N, optionally from 90 N to 370 N, such as from 100 N to 330 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8.

[0061] Suitably, in the unit dose pharmaceutical composition, the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, and suitably, the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core. Suitably, the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core.

[0062] Suitably, in the unit dose pharmaceutical composition, the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and suitably, the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core.

[0063] Suitably, in the unit dose pharmaceutical composition, the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and suitably the total amount of colesevelam and / or pharmaceutically acceptable salts present in the unit dose pharmaceutical composition is present in an amount of at least 76 wt% of the tablet core, and suitably, the total amount of colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of from 700 mg to 1200 mg in the tablet core, preferably from 850 mg to 1100 mg in the tablet core, such as about 900 mg in the tablet core.

[0064] Suitably, the diluent is selected from one or more of mannitol, sucrose and cellulose, and is present in an amount of from 6 wt% to 18 wt% of the tablet core, and the binder is polyvinyl pyrrolidone and is present in an amount of from 2 wt% to 4 wt% of the tablet core.

[0065] Suitably, the colesevelam and / or pharmaceutically acceptable salt thereof is colesevelam hydrochloride.

[0066] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 50% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in aUSP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0067] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 45% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0068] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 40% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0069] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 35% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0070] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 30% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP)dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0071] Suitably, any of the oral pharmaceutical compositions disclosed herein, may release not more than about 25% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0072] Suitably, any of the oral pharmaceutical compositions disclosed herein, may release not more than about 20% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0073] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 50% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0074] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 45% of the amount of colesevelam, or a pharmaceutically acceptable saltthereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0075] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 40% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0076] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 35% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0077] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 30% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0078] Suitably, any of the oral pharmaceutical compositions disclosed herein, may release not more than about 25% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0079] Suitably, any of the oral pharmaceutical compositions disclosed herein, may release not more than about 20% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0080] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 50% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0081] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 45% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolutionapparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0082] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 40% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0083] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 35% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0084] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 30% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0085] Suitably, any of the oral pharmaceutical compositions disclosed herein, may release not more than about 25% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases notless than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0086] Any of the oral pharmaceutical compositions disclosed herein may release not more than about 20% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0087] Optionally, the pharmaceutical composition releases not more than about 50% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0088] Optionally, the pharmaceutical composition releases not more than about 45% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0089] Optionally, the pharmaceutical composition releases not more than about 40% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0090] Optionally, the pharmaceutical composition releases not more than about 35% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer(optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0091] Optionally, the pharmaceutical composition releases not more than about 30% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0092] Optionally, the pharmaceutical composition releases not more than about 25% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0093] Optionally, the pharmaceutical composition releases not more than about 20% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0094] Optionally, the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0095] Optionally, the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0096] Optionally, the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP<711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0097] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 50% over about 1 hour, when measured at about pH 6.8.

[0098] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 45% over about 1 hour, when measured at about pH 6.8.

[0099] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 40% over about 1 hour, when measured at about pH 6.8.

[0100] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 35% over about 1 hour, when measured at about pH 6.8.

[0101] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 30% over about 1 hour, when measured at about pH 6.8.

[0102] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 25% over about 1 hour, when measured at about pH 6.8.

[0103] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 20% over about 1 hour, when measured at about pH 6.8.

[0104] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate of greater than or equal to about 80% of colesevelam, or a pharmaceutically acceptable salt thereof, over about 2 hours, when measured at about pH 6.8.

[0105] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate of greater than or equal to about 80% of colesevelam, or a pharmaceutically acceptable salt thereof, over about 3 hours, when measured at about pH 6.8.

[0106] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate of greater than or equal to about 80% of colesevelam, or a pharmaceutically acceptable salt thereof, over about 4 hours, when measured at about pH 6.8.

[0107] According to the invention, the dissolutions are measured with the with the USP dissolution apparatus type II equipped with a paddle at 100 rpm at 37°±2° C.

[0108] In another aspect the present invention provides a method of manufacturing a unit dose pharmaceutical composition for oral administration comprising:coating a tablet core with a gastro resistant coating, wherein the tablet core comprises: a granulate component and a non-granulate component, wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder, wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof, and optionally, one or more of a diluent, a disintegrant, a glidant and a lubricant, and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core.

[0109] In another aspect the present invention provides a method of manufacturing a unit dose pharmaceutical composition for oral administration comprising the steps of:(i) providing a tablet core wherein the tablet core comprises: a granulate component and a non-granulate component, wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder, wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof, and optionally, one or more of a diluent, a disintegrant, a glidant and a lubricant, and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core; and(ii) coating the tablet core with a gastro resistant coating.

[0110] The non-granulate component may comprise one or more of a diluent, a disintegrant, a glidant and a lubricant. For example, the non-granulate component may comprise two or more, or three or more, or all of a diluent, a disintegrant, a glidant and a lubricant.

[0111] Suitably, the non-granulate component comprises a diluent. Suitably, the non- granulate component comprises a disintegrant. Suitably, the non-granulate component comprises a glidant. Suitably, the non-granulate component comprises a lubricant. Optionally, the non-granulate component comprises a diluent and a disintegrant. Optionally, the non- granulate component comprises a diluent, a disintegrant and a glidant. Optionally, the non- granulate component comprises a diluent, a disintegrant, a glidant and a lubricant.

[0112] The method may optionally comprise the step of providing a sub-coating between the non-granulate component and the gastro-resistant coating.

[0113] Suitably, the method may comprise the steps of:(i) combining colesevelam and / or pharmaceutically acceptable salts thereof, a diluent and a binder, to form granules;(ii) combining colesevelam and / or pharmaceutically acceptable salts thereof and, optionally one or more of a diluent, a disintegrant, a glidant and a lubricant, with the granules of step (i), to form a tablet core having a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof, and, optionally, a diluent, a disintegrant, a glidant and lubricants; wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core; and coating the tablet core with a gastro resistant coating and optionally with a sub-coating between the tablet core and the gastro resistant coating.

[0114] The method may comprise dry or wet granulation, preferably wet granulation.

[0115] The wet granulation may be carried out using an aqueous or non-aqueous solvent, preferably a non-aqueous solvent, such as an organic solvent. Optionally, the organic solvent may be an alcohol, a ketone or a chlorinated solvent. Suitably, the alcohol is selected from methanol, ethanol, propanol and isopropanol, or mixtures thereof. Preferably, the alcohol is ethanol.

[0116] The method may involve bulk manufacture of a plurality of unit doses.

[0117] For example, the method may involve bulk manufacture of a plurality of unit doses comprising a pharmaceutical composition for oral administration, wherein the plurality of unit doses has a deviation from the uniformity of mass of less than ±2%, preferably less than ±1%, more preferably less than ±0.8%. For example, the plurality of unit doses has a uniformity of mass with a deviation from the average mass of less than ±2%, preferably less than ±1%, more preferably less than ±0.8%.

[0118] The obtained tablets are tested in a dissolution test USP <711> apparatus II, 0.1 N HCI for 2 hours and then 8 hours at pH 6.8 (phosphate buffer). To 1000 ml of phosphate buffer at pH 6.8 a fixed amount of sodium taurodeoxycholate is added. Coated tablets remain intact for 2 hours in 0.1 N HCI. Thereafter the tablets are withdrawn from the above medium and after draining are placed in the pH 6.8 medium. The coating starts to dissolve, the colesevelam starts to swell and binds the taurodeoxycholate in the medium. The dissolution of colesevelam along time is calculated by difference on the residual amount of free, non-bound taurodeoxycholate in the medium.

[0119] The present disclosure provides a unit dose oral pharmaceutical composition (or one or more unit doses) as described herein for use in a method of treating bile acid diarrhea, irritable bowel syndrome, optionally, irritable bowel syndrome subtype diarrhea (IBS-D), colitis, such as microscopic colitis, and / or bile acid malabsorption in a patient in need thereof, optionally, wherein the method comprises administering more than one of said unit dose oral pharmaceutical compositions to said patient.

[0120] The present disclosure provides further provides a method of treating bile acid diarrhea, irritable bowel syndrome, optionally, irritable bowel syndrome subtype diarrhea (IBS-D), colitis, such as microscopic colitis, and / or bile acid malabsorption in a patient in need thereof, comprising administering to said patient a unit does oral pharmaceutical composition as described herein, optionally, wherein the method comprises administering more than one of said unit dose oral pharmaceutical compositions to said patient.

[0121] The pharmaceutical compositions of the present invention can be used in the treatment of bile acid diarrhea. This bile acid diarrhea may be idiopathic (e.g., primary bile acid diarrhea) or secondary to an underlying disease. The underlying disease can be: Crohn’s disease, ileal resection or radiation ileitis, chronic pancreatitis, celiac disease, cholecystectomy, small intestine bacterial overgrowth, irritable bowel syndrome subtype diarrhea (IBS-D) and similar.

[0122] Suitably, the method of treating bile acid diarrhea comprises administering to a subject in need thereof, a therapeutically effective amount of a pharmaceutical composition described herein. The unit dose oral pharmaceutical composition can be administered either in a single non-fractionated administration or in multiple fractionated administrations.

[0123] The present invention allows for a reduction in the number of tablets and frequency of administration per day (e.g., two tablets twice per day, or one tablet twice per day) in comparison to current treatments, thus advantageously leading to an improvement in patient compliance. The pharmaceutical compositions of the present invention can be used in the treatment of irritable bowel syndrome subtype diarrhea (IBS-D).

[0124] Suitably, the method of treating irritable bowel syndrome subtype diarrhea (IBS- D) comprises administering to a subject in need thereof, a therapeutically effective amount of a pharmaceutical composition described herein.

[0125] The pharmaceutical compositions of the present invention can be used in the treatment of microscopic colitis.

[0126] Suitably, the method of treating microscopic colitis comprises administering to a subject in need thereof, a therapeutically effective amount of a pharmaceutical compositiondescribed herein. The pharmaceutical compositions of the present invention can be used in the treatment of bile acid malabsorption.

[0127] Suitably, the method of treating bile acid malabsorption comprises administering to a subject in need thereof, a therapeutically effective amount of a pharmaceutical composition described herein. The tablets can be administered either in a single non-fractionated administration or in multiple fractionated administrations (e.g., six tablets once per day, or three tablets twice per day, or two tablets thrice per day).

[0128] The present invention also provides for the use of a unit dose pharmaceutical composition for oral administration as described herein, for treating bile acid diarrhea, irritable bowel syndrome, optionally, irritable bowel syndrome subtype diarrhea (IBS-D), colitis, such as microscopic colitis, and / or bile acid malabsorption in a patient in need thereof, wherein optionally said use comprises administering more than one of said unit dose oral pharmaceutical compositions to said patient.

[0129] Furthermore, the present invention provides for use of a unit dose pharmaceutical composition for oral administration as described herein in the manufacture of a medicament for treating bile acid diarrhea, irritable bowel syndrome, optionally, irritable bowel syndrome subtype diarrhea (IBS-D), colitis, such as microscopic colitis, and / or bile acid malabsorption.

[0130] The present invention provides: a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof and optionally one or more of: a diluent, a disintegrant, a glidant and a lubricant; wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 66 wt% of the tablet core, such as at least about 70 wt% of the tablet core.

[0131] The colesevelam and / or pharmaceutically acceptable salts thereof may be present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, preferably 30 to 50 wt% of the tablet core, such as 35 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, optionally, in an amount of from 36 to 45 wt% of the tablet core, such as from 37 to 45 wt% of the tablet core.

[0132] The colesevelam and / or pharmaceutically acceptable salts thereof may be present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core, preferably 30 to 50 wt% of the tablet core, such as 35 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, optionally, in an amount of from 36 to 45 wt% of the tablet core, such as from 37 to 45 wt% of the tablet core.

[0133] The colesevelam and / or pharmaceutically acceptable salts thereof may be present in an amount of at least 76 wt% of the tablet core, preferably at least 80 wt% of the tablet core, more preferably at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core.

[0134] The colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of from 400 mg to 1250 mg in the tablet core, preferably in an amount of from 400 mg to 1200 mg in the tablet core, such as from 700 to 1200 mg in the tablet core, more preferably in an amount of from 850 mg to 1100 mg in the tablet core.

[0135] The colesevelam and / or the pharmaceutically acceptable salts thereof may be present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, and wherein the colesevelam is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core, and wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in a total amount of at least 70 wt% of the tablet core.

[0136] The colesevelam and / or the pharmaceutically acceptable salts thereof may be present in the granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and wherein the colesevelam is present in the non- granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in a total amount of at least 76 wt% of the tablet core, and wherein the colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of from 700 mg to 1200 mg in the tablet core, preferably from 850 mg to 1100 mg in the tablet core, such as about 900 mg in the tablet core.

[0137] The tablet core may have a friability of < 1.0%, optionally, < 0.5%, preferably < 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0138] The tablet core may have a hardness of > 70 N, optionally > 80 N, optionally, > 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8.

[0139] Suitably, in the unit dose pharmaceutical composition of the present invention, colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 76 wt% to 90 wt%, suitably from 80 wt% to 90 wt%; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0140] Suitably, the colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of about 900 mg in the tablet core.

[0141] Suitably, the non-granulate component comprises one or more of a diluent, a disintegrant, a glidant and a lubricant; optionally, wherein the diluent is selected from one or more of polyols such as mannitol, lactose, sugars such as sucrose, dextrose, dextrates, sorbitol, fructose, inorganic salts such as dibasic and tribasic calcium phosphate, sodium chloride, starch, modified starch and derivatives thereof, cellulose, a cellulose derivative (i.e. cellulose derivatives such as, for example, methyl, ethyl, or hydroxyethyl cellulose), and kaolin; further optionally, wherein the diluent is present in an amount of from 5 to 20 wt% of the tablet core, such as from 6 to 18 wt% of the tablet core, preferably from 7 to 16 wt% of the tablet core, more preferably from 10 to 15 wt% of the tablet core; optionally, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol, copovidone, cellulose, a cellulose derivative (e.g. hydroxypropyl cellulose, hypromellose, ethyl cellulose), acacia gum, starch, and a polymethylacrylate, preferably polyvinyl pyrrolidone and / or poly vinyl alcohol; further optionally, wherein the binder is present in an amount of from 1 wt% to 5 wt% of the tablet core, preferably from 2 wt % to 4 wt% of the tablet core;optionally, wherein the disintegrant is selected from one or more of sodium carboxy methyl cellulose, such as cross-linked sodium carboxy methyl cellulose, crospovidone, bentonite, an algin (e.g., alginic acid or a salt thereof, such a sodium alginate), a gum and modified starch, preferably, wherein the disintegrant is cross-linked sodium carboxy methyl cellulose, further optionally, wherein the disintegrant is present in an amount of from 0.1 wt% to 7 wt% of the tablet core, preferably from 0.5 wt % to 5 wt%, such as from 1 to 2.5 wt% of the tablet core, more preferably from 1 to 2 wt% of the tablet core.

[0142] For example, a unit dose pharmaceutical composition of the present invention may comprise colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 81 wt% to 90 wt% of the tablet core, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein said diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein said binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 4 wt % of the tablet core; wherein the non-granulate component further comprises a lubricant and a glidant; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8, and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0143] Suitably, the gastro-resistant coating of the unit dose starts breaking or dissolving at or above a pH of 6.0, preferably at or above a pH of 6.5, more preferably at a pH of 6.8.

[0144] Preferably, the colesevelam and / or pharmaceutically acceptable salt thereof is colesevelam hydrochloride.

[0145] Also disclosed herein is: a method of manufacturing a unit dose pharmaceutical composition for oral administration comprising the steps of:(a) providing a tablet core wherein the tablet core comprises: a granulate component and a non-granulate component, wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder, wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof, and optionally, one or more of a diluent, a disintegrant, a glidant and a lubricant, and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 66 wt% of the tablet core, preferably at least 70 wt% of the tablet core; and(b) coating the tablet core with a gastro resistant coating and optionally a sub-coating.

[0146] The method may comprise the steps of:(i) combining colesevelam and / or pharmaceutically acceptable salts thereof, a diluent and a binder, to form a granulate;(ii) combining colesevelam and / or pharmaceutically acceptable salts thereof and, optionally, a diluent and a disintegrant, with the granulate of step (i), to form a tablet core having a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof, and, optionally, one or more of a diluent, a disintegrant, a glidant and lubricants; wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 66 wt% of the tablet core, preferably at least 70 wt% of the tablet core; and(iii) coating the tablet core with a gastro resistant coating and optionally a sub-coating; wherein optionally, step (i) involves wet granulation, further optionally, the wet granulation is carried out using water or a non-aqueous solvent, preferably a non-aqueous solvent, such as an organic solvent, such as an alcohol, preferably ethanol, a ketone or a chlorinated solvent.

[0147] The method may comprise bulk manufacture of a plurality of unit doses comprising a pharmaceutical composition for oral administration, wherein the plurality of unit doses has a deviation from the uniformity of mass of less than ±2%, preferably less than ±1%, more preferably less than ±0.8%. For example, the plurality of unit doses has a uniformity of mass with a deviation from the average mass of less than ±2%, preferably less than ±1%, more preferably less than ±0.8%.

[0148] Also disclosed is a unit dose pharmaceutical composition for oral administration as described herein for use in a method of treating bile acid diarrhea, irritable bowel syndrome, optionally, irritable bowel syndrome subtype diarrhea (IBS-D), colitis, such as microscopic colitis, and / or bile acid malabsorption in a patient in need thereof, optionally, wherein the method comprises administering more than one of said unit dose oral pharmaceutical compositions to said patient.

[0149] Disclosed herein is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride and optionally one or more of: a diluent, a disintegrant, a glidant and a lubricant; wherein the colesevelam hydrochloride is present in an amount of about 66 wt% to about 90 wt% of the tablet core.

[0150] For example, colesevelam hydrochloride may be present in the granulate component in an amount of from about 37 wt% to about 45 wt% of the tablet core. Colesevelam hydrochloride may be present in the non-granulate component in an amount of from about 37 wt% to about 45 wt% of the tablet core.

[0151] The colesevelam hydrochloride is present in an amount of from about 700 to about 1200 mg in the tablet core. Suitably, colesevelam hydrochloride is present in an amount of about 900 mg in the tablet core.DEFINITIONS

[0152] As used herein the term “active pharmaceutical ingredient” (“API”) or “pharmaceutically active agent” is a drug or agent which can be employed for the compositions and methods of the disclosure and is intended to be used in the human or animal body in order to heal, to alleviate, to prevent or to diagnose diseases, ailments, physical damage or pathological symptoms; allow the state, the condition or the functions of the body or mental states to be identified; to replace active substances produced by the human or animal body, or body fluids; to defend against, to eliminate or to render innocuous pathogens, parasites or exogenous substances or to influence the state, the condition or the functions of the body or mental states. Drugs in use can be found in reference works such as, for example, the Rote Liste or the Merck Index. Examples which may be mentioned include, for example, colesevelam.

[0153] As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the therapeutic compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of the active agent. The pharmaceutically acceptable salts include the conventional non-toxic salts, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfonic, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as amino acids, acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and other known to those of ordinary skill in the pharmaceutical sciences. Lists of suitable salts are found in texts such as Remington 's Pharmaceutical Sciences, 18th Ed. (Alfonso R. Gennaro, ed.; Mack Publishing Company, Easton, Pa., 1990); Remington: the Science and Practice of Pharmacy 19th Ed. (Lippincott, Williams & Wilkins, 1995); Handbook of Pharmaceutical Excipients, 3K| Ed. (Arthur H. Kibbe, ed.; Amer. Pharmaceutical Assoc., 1999); the Pharmaceutical Codex: Principles and Practice of Pharmaceutics 12th Ed. (Walter Lund ed.; Pharmaceutical Press, London, 1994); The United States Pharmacopeia: The National Formulary (United States Pharmacopeial Convention); and Goodman and Gilman's: the Pharmacological Basis of Therapeutics (Louis S. Goodman and Lee E. Limbird, eds.; McGraw Hill, 1992), the disclosures of which are hereby incorporated by reference.

[0154] An amount is "effective" as used herein, when the amount provides an effect in the subject. As used herein, the term "effective amount" means an amount of a compound or composition sufficient to significantly induce a positive benefit, including independently or in combinations the benefits disclosed herein, but low enough to avoid serious side effects, i.e., to provide a reasonable benefit to risk ratio, within the scope of sound judgment of the skilled artisan.For those skilled in the art, the effective amount, as well as dosage and frequency of administration, may be determined according to their knowledge and standard methodology of merely routine experimentation based on the present disclosure.

[0155] As used herein, the terms "subject" and "patient" are used interchangeably. As used herein, the term "patient" refers to an animal, preferably a mammal such as a non-primate (e.g., cows, pigs, horses, cats, dogs, rats etc.) and a primate (e.g., monkey and human), and most preferably a human. In some embodiments, the subject is a non-human animal such as a farm animal (e.g., a horse, pig, or cow) or a pet (e.g., a dog or cat). In a specific embodiment, the subject is an elderly human. In another embodiment, the subject is a human adult. In another embodiment, the subject is a human child. In yet another embodiment, the subject is a human infant.

[0156] As used herein, the phrase "pharmaceutically acceptable" means approved by a regulatory agency of the federal or a state government, or listed in the U.S. Pharmacopeia, European Pharmacopeia, or other generally recognized pharmacopeia for use in animals, and more particularly, in humans.

[0157] As used herein, the terms "prevent," "preventing" and "prevention" in the context of the administration of a therapy to a subject refer to the prevention or inhibition of the recurrence, onset, and / or development of a disease or condition, or a combination of therapies (e.g., a combination of prophylactic or therapeutic agents).

[0158] As used herein, the terms "therapies" and "therapy" can refer to any method(s), composition(s), and / or agent(s) that can be used in the prevention, treatment and / or management of a disease or condition, or one or more symptoms thereof.

[0159] As used herein, the terms "treat," "treatment," and "treating" in the context of the administration of a therapy to a subject referto the reduction or inhibition ofthe progression and / or duration of a disease or condition, the reduction or amelioration of the severity of a disease or condition, and / or the amelioration of one or more symptoms thereof resulting from the administration of one or more therapies.

[0160] As used herein, the term "about" when used in conjunction with a stated numerical value or range has the meaning reasonably ascribed to it by a person skilled in the art, i.e. denoting somewhat more or somewhat less than the stated value or range. For example, for each specified value “about” may be ±10%, suitably ±5%, suitably ±2%, suitably ±1%.

[0161] As used herein, the symbol "wt%" or “% w / w” indicates the weight percent of a substance in a mixture (e.g., a mixture of solid substances, or in a solution), which is calculated as the mass of the component divided by the total mass of the mixture and then multiplied by 100to provide the percentage. Usually, mass is expressed in grams, but any unit of measurement is acceptable as long as the same units for both the component or solute mass and the total or solution mass are used in the calculation.

[0162] Colesevelam hydrochloride is poly(allylamine hydrochloride) cross-linked with epichlorohydrin and alkylated with 1-bromodecane and (6-bromohexyl)-trimethylammonium bromide. The chemical name (IUPAC) of colesevelam hydrochloride is allylamine polymer with 1- chloro-2,3-epoxypropane,[6-(allylamino)-hexyl]trimethylammonium chloride and N- allyldecylamine, hydrochloride. The chemical structure of colesevelam hydrochloride is represented by the following formula:wherein (a) represents allyl amine monomer units that have not been alkylated by either of the 1- bromodecane or (6-bromohexyl)-trimethylammonium bromide alkylating agents or cross-linked by epichlorohydrin; (b) represents allyl amine units that have undergone cross-linking with epichlorohydrin; (c) represents allyl amine units that have been alkylated with a decyl group; (d) represents allyl amine units that have been alkylated with a (6-trimethylammonium) hexyl group, and m represents a number > 100 to indicate an extended polymer network. A small amount ofthe amines are dialkylated and are not depicted in the formula above. No regular order of the groups is implied by the structure; cross-linking and alkylation are expected to occur randomly along the polymer chains. A large amount of the amines are protonated. The polymer is depicted in the hydrochloride form; a small amount of the halides are bromide. Colesevelam hydrochloride is hydrophilic and insoluble in water. Preferably, the present invention employs colesevelam hydrochloride, however, the person skilled in the art will appreciate that alternative pharmaceutically acceptable salts, or the free base version of colesevelam may be employed in the present invention.Brief Description of the Drawings

[0163] FIG. 1 shows the binding capacity of colesevelam HCI for taurodeoxycholate (DS) over time. The Y axis label “% vs DS”, refers to the binding capacity of colesevelam hydrochloride versus the maximum binding capacity of the drug substance (colesevelam raw material). A unit dose pharmaceutical composition tablet according to the invention as described in Example 2B (Formulation G2, coated in the same manner as Formulation F described below) was added to 0.1 N HCI for 2 hours, and then the tablets (which remained intact during the course of the acid treatment and were drained of any residual acid) were added to phosphate buffer medium at pH 6.8 comprising a known amount of taurodeoxycholate. As the gastric resistant coating of the tablet dissolves (at pH 6.8) colesevelam HCI is released and swells and binds the taurodeoxycholate in the medium. The amount of unbound taurodeoxycholate is monitored over time, and the binding capacity of colesevelam is calculated by the consumption of the free nonbound taurodeoxycholate.DETAILED DESCRIPTION

[0164] The present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof and optionally one or more of a diluent, a disintegrant, a glidant and a lubricant; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 66 wt% of the tablet core.

[0165] The present inventors discovered that tablet cores having a surprisingly high loading of colesevelam and / or a pharmaceutically acceptable salt thereof could unexpectedly be manufactured by splitting a high dose of colesevelam and / or pharmaceutically acceptable salts thereof into a granulate component and a non-granulate component, and tabletting said granulate and non-granulate components. In particular, and without wishing to be bound by a particular theory, the inventors believe that providing a unit dose pharmaceutical composition comprising colesevelam hydrochloride in granulate and non-granulate components enables preparation of tablets having excellent hardness and low friability. Tablets having these qualities are suitable for manufacturing, transportation, and storage, and as discussed elsewhere herein, due to their high API loading, enable physicians to reduce the number of tablets patients are required to consume. Because patients are required to consume fewer tablets throughout the course of the day, there is an increased likelihood of patient compliance with a prescribed dosing regimen, and relatedly, increased efficacy. Importantly, preparing tablets having an increased concentration of colesevlam hydrochloride and the presently noted mechanical properties was not a mere optimization or revision of certain prior art formulation disclosed, for example, in WO2021 / 163007. As described in detail elsewhere herein, the formulations described in W02021 / 163007 were either unsuitable for tableting altogether at the desired API loading or were unable to provide tablets having both the desired API loading and mechanical properties necessary for manufacturing, transportation, and storage. Thus, the inventors, through the extensive research and development described herein, solved the problem of providing colesevelam unit dosage forms for oral administration having high colesevlam loading and suitable mechanical properties - a problem the prior art did not recognize or provide any guidance on solving. In particular, the inventors, through the extensive trial and error detailed elsewhere herein, solved the problem of providing colesevelam hydrochloride unit dosage forms having high colesevlam hydrochloride loading and suitable mechanical properties - a problem the prior art did not recognize or provide any guidance on solving.

[0166] The total amount of colesevelam and / or pharmaceutically acceptable salts thereof in the unit dose pharmaceutical composition for oral administration accounts for at least 66 wt% of the tablet core, such as at least about 70 wt% of the tablet core. The total amount of colesevelam and or pharmaceutically acceptable salts thereof in the unit dose includes the amount of colesevelam and / or pharmaceutically acceptable salts thereof in the granulate component and in the non-granulate component. The granulate component colesevelam and / or a pharmaceutically acceptable salt thereof, diluent, and a binder. For example, the granulate component comprises granules comprising colesevelam and / or a pharmaceutically acceptable salt thereof, diluent, and a binder. The granulate is manufactured by granulation using a granulator.

[0167] The unit dose oral pharmaceutical composition (or one or more unit doses) of the present invention may be used to treat diseases or conditions such as bile acid diarrhea, irritablebowel syndrome, optionally, irritable bowel syndrome subtype diarrhea (IBS-D), colitis, such as microscopic colitis, and / or bile acid malabsorption in a patient in need thereof. The treatment may comprise administering more than one of said unit dose oral pharmaceutical compositions to said patient.

[0168] Given the chronicity of the aforementioned diseases / conditions, treatment with prior art or commercially available colesevelam tablets which comprise lower amounts and loadings of colesevelam requires the administration of a large number of tablets per day. This often leads to patient compliance issues. Advantageously, the unit dose oral pharmaceutical composition of the present invention allows for a reduction in the number of tablets and a reduction in the frequency of administration per day (e.g, two tablets twice per day, or one tablet twice per day), which leads to an improvement in patient compliance.

[0169] As outlined above, the amounts of colesevelam or pharmaceutically acceptable salts thereof refer to amounts of the anhydrous substances (i.e., dry weight percentages). The colesevelam or pharmaceutically acceptable salts thereof suitable for the present invention may comprise some amount of water, i.e., hydrated colesevelam or pharmaceutically acceptable salts thereof may be used, however, the amount of hydrated colesevelam or pharmaceutically acceptable salts thereof used is determined based on a dry weight percentage. Suitably, such hydrated colesevelam or pharmaceutically acceptable salts thereof comprise less than about 20 wt% of the total weight of the hydrated substance, preferably less than about 10 wt%, e.g., 1 wt%, or 2 wt%, or 3 wt%, or 4 wt%, or 5 wt%, or 6 wt%, or 7 wt%, or 8 wt%, or 9 wt%, or any fractions of the above integers. As known in the art, such amount of water shall be compensated through an overweight of colesevelam or salts thereof in order to achieve the target amounts according to the present disclosure.

[0170] Suitably, the non-granulate component is a powder or pulverulent substance.

[0171] Suitably, the granulate component is a granulate formed by a granulation method, for example using a granulator.

[0172] Suitably, the granulate component comprises granules having a particle size distribution with a D50 between 125 and 250 pm and a D90 of not more than 850 pm as determined in accordance with European Pharmacopoeia monograph 2.9.38 or US Pharmacopoeia monograph <786>.

[0173] The colesevelam and / or pharmaceutically acceptable salts thereof may be present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, optionally 30 to 50 wt% of the tablet core, such as 35 to 50 wt% of the tablet core, optionally 35 to 45 wt% of the tablet core, further optionally in an amount of from 36 to 45 wt% of the tablet core, or 37 to 45 wt% of the tablet core. For example, the colesevelam and / or pharmaceutically acceptablesalts thereof may be present in the granulate component in an amount of from 35 to 45 wt% of the tablet core, such as in an amount of from 36 to 44 wt% of the tablet core, such as in an amount of from 37 to 43 wt% of the tablet core. By way of further example, the colesevelam hydrochloride may be present in the granulate component in an amount of from 35 to 45 wt% of the tablet core, such as in an amount of from 36 to 44 wt% of the tablet core, such as in an amount of from 37 to 43 wt% of the tablet core.

[0174] The colesevelam and / or pharmaceutically acceptable salts thereof may be present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, such as 30 wt%, or 31 wt%, or 32 wt% or 33 wt%, or 34 wt%, or 35 wt%, or 36 wt%, or 37 wt%, or 38 wt%, or 39 wt%, or 40 wt%, or 41 wt%, or 42 wt%, or 43 wt%, or 44 wt%, or 45 wt%, or 46 wt%, or 47 wt%, or 48 wt%, or 49 wt%, or 50 wt%, or 51 wt%, or 52 wt%, or 53 wt%, or 54 wt%, or 55 wt%, or 56 wt%, or 57 wt%, or 58 wt%, or 59 wt%, or 60 wt%.

[0175] Preferably, the colesevelam and / or pharmaceutically acceptable salts thereof may be present in the granulate component in an amount of 45 wt% of the tablet core, preferably of 47.5 wt%, more preferably of 50 wt%. For example, colesevelam hydrochloride may be present in the granulate component in an amount of 45 wt% of the tablet core, preferably of 47.5 wt%, more preferably of 50 wt%.

[0176] The colesevelam and / or pharmaceutically acceptable salts thereof may be present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core, optionally 30 to 50 wt% of the tablet core, optionally 35 to 45 wt% of the tablet core, further optionally in an amount of from 36 to 45 wt% of the tablet core, such as in an amount of from 37 to 45 wt% of the tablet core. For example, the colesevelam and / or pharmaceutically acceptable salts thereof may be present in the granulate component in an amount of from 35 to 45 wt% of the tablet core, such as in an amount of from 36 to 44 wt% of the tablet core, such as in an amount of from 37 to 43 wt% of the tablet core. By way of further example, colesevelam hydrochloride may be present in the granulate component in an amount of from 35 to 45 wt% of the tablet core, such as in an amount of from 36 to 44 wt% of the tablet core, such as in an amount of from 37 to 43 wt% of the tablet core.

[0177] The colesevelam and / or pharmaceutically acceptable salts thereof may be present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core, such as 30 wt%, or 31 wt%, or 32 wt% or 33 wt%, or 34 wt%, or 35 wt%, or 36 wt%, or 37 wt%, or 38 wt%, or 39 wt%, or 40 wt%, or 41 wt%, or 42 wt%, or 43 wt%, or 44 wt%, or 45 wt%, or 46 wt%, or 47 wt%, or 48 wt%, or 49 wt%, or 50 wt%, or 51 wt%, or 52 wt%, or 53 wt%, or 54 wt%, or 55 wt%, or 56 wt%, or 57 wt%, or 58 wt%, or 59 wt%, or 60 wt%.

[0178] Preferably, the colesevelam and / or pharmaceutically acceptable salts thereof may be present in the non-granulate component in an amount of 45 wt% of the tablet core,preferably of 47.5 wt%, more preferably of 50 wt%. For example, colesevelam hydrochloride may be present in the non-granulate in an amount of 45 wt% of the tablet core, preferably of 47.5 wt%, more preferably of 50 wt%.

[0179] The colesevelam and / or the pharmaceutically acceptable salts thereof may be present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, and the colesevelam may be present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core, and the colesevelam and / or pharmaceutically acceptable salts thereof is present in a total amount of at least 70 wt% of the tablet core.

[0180] Friability of the tablet cores is reduced ( i.e. , the tablet cores are less friable) when the colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, optionally 30 to 50 wt% of the tablet core, optionally 35 to 45 wt% of the tablet core, such as from 36 wt% to 45 wt%, for example 37 wt% to 45 wt% of the tablet core; and when the colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core, optionally 30 to 50 wt% of the tablet core, optionally 35 to 45 wt% of the tablet core, such as from 36 wt% to 45 wt%, for example 37 wt% to 45 wt% of the tablet core. In particular aspects, friability of the tablet cores is reduced when the colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, optionally 30 to 50 wt% of the tablet core, optionally 35 to 45 wt% of the tablet core, such as from 36 wt% to 45 wt%, for example 37 wt% to 45 wt% of the tablet core; and when colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core, optionally 30 to 50 wt% of the tablet core, optionally 35 to 45 wt% of the tablet core, such as from 36 wt% to 45 wt%, for example 37 wt% to 45 wt% of the tablet core.

[0181] If less than about 30 wt% of the tablet core of colesevelam is contained in the non-granulate component hardness is reduced and friability is increased.

[0182] Together the amount of colesevelam and / or pharmaceutically acceptable salts thereof in the non-granulate component and the amount in the granulate component account for at least 70 wt% of the tablet core. For example, the amount of colesevelam hydrochloride in the non-granulate component and the amount in the granulate component account for at least 70 wt% of the tablet core.

[0183] Suitably, colesevelam and / or pharmaceutically acceptable salts thereof is present (in the unit dose pharmaceutical composition for oral administration) in an amount of at least 70 wt% or at least 75 wt% or at least 76 wt% of the tablet core, suitably at least 80 wt% of the tablet core, more suitably at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core. For example, and in some aspects, colesevelam hydrochloride is present (in the unit dose pharmaceutical composition for oral administration) in an amount of at least 70 wt% or at least 75wt% or at least 76 wt% of the tablet core, suitably at least 80 wt% of the tablet core, more suitably at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core.

[0184] Suitably, colesevelam and / or pharmaceutically acceptable salts thereof is present (in the unit dose pharmaceutical composition for oral administration) form in an amount of at least 70 wt% of the tablet core, such as at least 71 wt%, or at least 72 wt%, or at least 73 wt%, or at least 74 wt%, or at least 75 wt%, or at least 76 wt%, or at least 77 wt%, or at least 78 wt%, or at least 79 wt%, or at least 80 wt%, or at least 81 wt%, or at least 82 wt%, or at least 83 wt%, or at least 84 wt%, or at least 85 wt%, or at least 86 wt%, or at least 87 wt%, or at least 88 wt%, or at least 89 wt%, or at least 90 wt%, of the tablet core. For example, and in some aspects, colesevelam hydrochloride is present (in the unit dose pharmaceutical composition for oral administration) in an amount of at least 70 wt% of the tablet core, such as at least 71 wt%, or at least 72 wt%, or at least 73 wt%, or at least 74 wt%, or at least 75 wt%, or at least 76 wt%, or at least 77 wt%, or at least 78 wt%, or at least 79 wt%, or at least 80 wt%, or at least 81 wt%, or at least 82 wt%, or at least 83 wt%, or at least 84 wt%, or at least 85 wt%, or at least 86 wt%, or at least 87 wt%, or at least 88 wt%, or at least 89 wt%, or at least 90 wt%, of the tablet core.

[0185] Preferably, colesevelam and / or pharmaceutically acceptable salts thereof is present in the unit dose pharmaceutical composition for oral administration in an amount of at least 75 wt% of the tablet core, such as in an amount of at least 76 wt% of the tablet core, preferably at least 80 wt% of the tablet core, more preferably at least 81 wt% of the tablet core, optionally, at least 82 wt% of the tablet core. In typical aspects, the colesevelam present in the unit dose pharmaceutical composition for oral administration in the amounts noted herein is colesevelam hydrochloride.

[0186] For example, colesevelam and / or pharmaceutically acceptable salts thereof is present in the unit dose pharmaceutical composition for oral administration in an amount of 70 wt% to 90 wt% of the tablet core, or in an amount of 75 wt% to 90 wt% of the tablet core, or in an amount of 76 wt% to 90 wt% of the tablet core, suitably in an amount of 80 wt% to 90 wt% of the tablet core, more suitably 81 wt% to 90 wt% of the tablet core, optionally 82 wt% to 90 wt% of the tablet core. Optionally, colesevelam and / or pharmaceutically acceptable salts thereof is present in the unit dose pharmaceutical composition for oral administration in an amount of 70 wt% to 88 wt% of the tablet core, or in an amount of 75 wt% to 88 wt% of the tablet core, or in an amount of 76 wt% to 88 wt% of the tablet core, suitably in an amount of 80 wt% to 88 wt% of the tablet core, more suitably 81 wt% to 88 wt% of the tablet core, optionally 82 wt% to 88 wt% of the tablet core. Further optionally, colesevelam and / or pharmaceutically acceptable salts thereof is present in the unit dose pharmaceutical composition for oral administration in an amount of 70 wt% to 85 wt% of the tablet core, or in an amount of 75 wt% to 85 wt% of the tablet core, or in an amount of 76 wt% to 85 wt% of the tablet core, suitably in an amount of 80 wt% to 85 wt% of the tablet core, more suitably 81 wt% to 85 wt% of the tablet core, optionally 82 wt% to 85 wt% of the tablet core.

[0187] In another example, colesevelam hydrochloride is present in the unit dose pharmaceutical composition for oral administration in an amount of 70 wt% to 90 wt% of the tablet core, or in an amount of 75 wt% to 90 wt% of the tablet core, or in an amount of 76 wt% to 90 wt% of the tablet core, suitably in an amount of 80 wt% to 90 wt% of the tablet core, more suitably 81 wt% to 90 wt% of the tablet core, optionally 82 wt% to 90 wt% of the tablet core. Optionally, colesevelam hydrochloride is present in the unit dose pharmaceutical composition for oral administration in an amount of 70 wt% to 88 wt% of the tablet core, or in an amount of 75 wt% to 88 wt% of the tablet core, or in an amount of 76 wt% to 88 wt% of the tablet core, suitably in an amount of 80 wt% to 88 wt% of the tablet core, more suitably 81 wt% to 88 wt% of the tablet core, optionally 82 wt% to 88 wt% of the tablet core. Further optionally, colesevelam hydrochloride is present in the unit dose pharmaceutical composition for oral administration in an amount of 70 wt% to 85 wt% of the tablet core, or in an amount of 75 wt% to 85 wt% of the tablet core, or in an amount of 76 wt% to 85 wt% of the tablet core, suitably in an amount of 80 wt% to 85 wt% of the tablet core, more suitably 81 wt% to 85 wt% of the tablet core, optionally 82 wt% to 85 wt% of the tablet core.

[0188] Preferably, colesevelam and / or pharmaceutically acceptable salts thereof is present in the unit dose pharmaceutical composition for oral administration in an amount of from 75 wt% to 90 wt% of the tablet core, preferably in an amount of from 80 wt% to 90 wt% of the tablet core, more preferably in an amount of from 81 wt% to 90 wt% of the tablet core. For example, colesevelam and / or pharmaceutically acceptable salts thereof may be present in the unit dose pharmaceutical composition for oral administration in an amount of from 75 wt% to 90 wt% of the tablet core, optionally, in an amount of from 80 wt% to 88 wt% of the tablet core, optionally in an amount of from 81 wt% to 85 wt% of the tablet core, optionally 82 wt% to 85 wt% of the tablet core. For example, colesevelam hydrochloride is present in the unit dose pharmaceutical composition for oral administration in an amount of from 75 wt% to 90 wt% of the tablet core, preferably in an amount of from 80 wt% to 90 wt% of the tablet core, more preferably in an amount of from 81 wt% to 90 wt% of the tablet core. By way of further example, colesevelam hydrochloride may be present in the unit dose pharmaceutical composition for oral administration in an amount of from 75 wt% to 90 wt% of the tablet core, optionally, in an amount of from 80 wt% to 88 wt% of the tablet core, optionally in an amount of from 81 wt% to 85 wt% of the tablet core, optionally 82 wt% to 85 wt% of the tablet core.

[0189] Suitably, the colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of from 400 mg to 1250 mg in the tablet core, preferably in an amount of from 400 mg to 1200 mg in the tablet core, such as from 700 to 1200 mg in the tablet core, more preferably in an amount of from 850 mg to 1100 mg in the tablet core. Suitably, the colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of about 900 mg in the tablet core. For example, the colesevelam hydrochloride is present in an amount of from 400 mg to 1250 mg in the tablet core, preferably in an amount of from 400 mg to 1200 mg in the tabletcore, such as from 700 to 1200 mg in the tablet core, more preferably in an amount of from 850 mg to 1100 mg in the tablet core. Suitably, the colesevelam hydrochloride is present in an amount of about 900 mg in the tablet core.

[0190] The unit dose may be formulated for delayed release, optionally for delayed release in the ileum. The unit dose may be formulated for extended release, optionally for extended release starting in the ileum and continuing into the initial portion of the colon. The unit dose may be formulated for delayed / extended release, optionally for delayed release in the ileum and extended release continuing into the initial portion of the colon.

[0191] The unit dose may be formulated for release starting and reaching 100% release in the ileum prior to entering the ascending colon. The unit dose may be formulated for release starting in the ileum and continuing into the initial portion of the ascending colon. The unit dose may be formulated for release starting in the ileum and continuing throughout the ascending colon. The unit dose may be formulated for release starting in the ileum and continuing throughout the ascending and transverse colon. The unit dose may be formulated for release starting in the ileum and continuing throughout the ascending colon, transverse colon and descending colon. The unit dose may be formulated for release starting in the ileum and continuing throughout the ascending colon, transverse colon, descending colon and sigmoid colon. The unit dose may be formulated for release starting in the ileum and continuing throughout the ascending colon, transverse colon, descending colon, sigmoid colon and rectum.

[0192] The non-granulate component of the unit dose pharmaceutical composition may also comprise a diluent.

[0193] The diluent (of the granulate component and / or non-granulate component) may be selected from one or more of polyols such as mannitol, lactose, sugars as sucrose, dextrose, dextrates, sorbitol, fructose; inorganic salts such as dibasic and tribasic calcium phosphate sodium chloride, starch, modified starch and derivatives thereof, cellulose, and a cellulose derivative (i.e. cellulose derivatives such as, for example, methyl, ethyl or hydroxyethyl cellulose or similar), and kaolin. Suitably, wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, a cellulose derivative. The diluent may be present in an amount of from 5 wt% to 20 wt% of the tablet core, such as from 6 wt% to 18 wt% of the tablet core, optionally from 7 wt% to 16 wt% of the tablet core, optionally from 10 wt% to 15 wt% of the tablet core.

[0194] The binder may be selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, acacia gum, cellulose, and a cellulose derivative (e.g., hydroxypropyl cellulose, hypromellose, or ethyl cellulose), a polymethacrylate and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol.

[0195] The binder may be present in an amount of from 1 wt% to 5 wt% of the tablet core, optionally from 1 wt% to 4 wt%, such as from 2 wt % to 4 wt% of the tablet core.

[0196] The composition may optionally include a disintegrant. The disintegrant may be selected from one or more of sodium carboxy methyl cellulose, such as cross-linked sodium carboxy methyl cellulose, crospovidone, bentonite, an algin (e.g., alginic acid or a salt thereof, such as sodium alginate), a gum, starch, and modified starch, preferably, wherein the disintegrant is cross-linked sodium carboxy methyl cellulose or modified starch.

[0197] The unit dose pharmaceutical composition may comprise a disintegrant.

[0198] The disintegrant may be present in an amount of from 0.1 wt% to 7 wt%, optionally, from 0.5 to 5 wt% of the tablet core, optionally from 1 wt % to 2.5 wt% of the tablet core, optionally from 1 to 2 wt% of the tablet core.

[0199] Suitably, the disintegrant is present in the non-granulate component of the unit dose pharmaceutical composition.

[0200] The unit dose pharmaceutical composition may further comprise a glidant and / or lubricant.

[0201] The glidant may be selected from the group comprising: talc, starch, magnesium oxide, silica (silicon dioxide) and a silicate, such as magnesium or calcium silicate. Preferably, the glidant is colloidal silicon dioxide, silica, talc or magnesium oxide.

[0202] The lubricant may be selected from the group comprising: stearic acid and salts thereof (e.g. magnesium, calcium or zinc stearate), polyethylene glycol, fumaric acid and salts thereof, glyceryl behenate, glyceryl palmitostearate, wax, poloxamer, sodium benzoate, and any combination thereof. Preferably, the lubricant is stearic acid or a salt thereof (e.g., magnesium stearate), fumaric acid or a salt thereof, or polyethylene glycol.

[0203] The glidant may be present in an amount of from 0.1 to 2 wt% of the tablet core, optionally the glidant is present in an amount of from 0.5 to 1 wt% of the tablet core.

[0204] The lubricant may be present in an amount of from 0.1 to 2 wt% of the tablet core, optionally the lubricant is present in an amount of from 0.5 to 1 wt% of the tablet core.

[0205] The unit dose pharmaceutical composition may further comprise a sub-coating between the tablet core and the gastro-resistant coating, wherein optionally, the sub-coating comprises hydroxypropyl cellulose.

[0206] The gastro-resistant coating (film) covering the tablet core may contain polymethacrylates, acrylic and / or methacrylic acids polymers or copolymers or cellulose derivatives, such as cellulose acetophthalate. Optionally, the g astro-protective coating comprises methacrylic acid / methyl methacrylate (1:1 ) copolymer (e.g. , commercially known as EUDRAGIT L). Optionally, the gastro-resistant coating comprises methacrylic acid / methyl methacrylate (1 :2) copolymer (e.g., commercially known as EUDRAGIT S). Optionally, the gastro-protective coating comprises methacrylic acid-ethylacrylate (1:1) copolymer (e.g., commercially known as EUDRAGIT L30 D55). Optionally, the gastro-protective coating comprises polymethacrylate copolymers including, but not limited, to compounds known commercially as EUDRAGIT S (methacrylic acid-methyl methacrylate copolymer 1 :2), EUDRAGIT L (methacrylic acid- methyl methacrylate 1 :1 copolymer) and / or EUDRAGIT L30 D55 (methacrylic acid-ethylacrylate 1 :1 copolymer), and / or mixtures thereof. The gastro resistant coating may comprise a methacrylic acid — (meth Jacrylate copolymer. Suitably, the gastro resistant coating comprises methacrylic acid / methyl methacrylate copolymer.

[0207] The gastro-resistant coating may comprise methacrylic acid / methyl methacrylate (1:1 ) copolymer (EUDRAGIT L), or methacrylic acid / methyl methacrylate (1:2) copolymer (EUDRAGIT S).

[0208] The gastro-resistant coating may comprise a mixture of methacrylic acid / methyl methacrylate (1 :1 ) copolymer and of methacrylic acid / methyl methacrylate (1 :2) copolymer. Optionally, the mixture comprises a weight ratio of 0.5:1 to 3:1 of methacrylic acid / methyl methacrylate (1: 1) copolymer to methacrylic acid / methyl methacrylate (1:2). Optionally, the mixture comprises a weight ratio of 1 :1 to 3:1 of methacrylic acid / methyl methacrylate (1 :1 ) copolymer to methacrylic acid / methyl methacrylate (1 :2). Preferably, the mixture comprises a weight ratio of about 2:1 of methacrylic acid / methyl methacrylate (1 :1 ) copolymer to methacrylic acid / methyl methacrylate (1 :2).

[0209] The gastro-resistant coating of the unit dose suitably starts breaking or dissolving at or above a pH of 5, preferably at or above a pH of 6, more preferably at or above a pH of 6.5, much more preferably at a pH at or about of 6.8.

[0210] Suitably, the active substance is released from the tablet core at pH of at least 5, such as 5.1 , or 5.2, or 5.3, or 5.4, or 5.5, or 5.6, or 5.7, or 5.8, or 5.9, or 6, or 6.1, or 6.2, or 6.3, or 6.4, or 6.5, or 6.6, or 6.7, or 6.8, or 6.9, or 7, or 7.1 , or 7.2, or 7.3, or 7.4, or 7.5. Preferably, the active substance is released from the tablet core at pH in the range from about 6.5 to about 7.5, optionally, at a pH in the range of from about 6.8 to about 7. According to a preferred aspect, the active substance is released from the tablet core at pH of 6.8. According to another preferred aspect, the active substance is released from the tablet core at pH of 7. According to a further preferred aspect, the active substance is released from the tablet core at pH of 7.2.

[0211] The tablet core has a friability of less than about 1.0%, optionally, less than about 0.5%, preferably less than about 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7. For example, the tablet core may have a friability of 0.001 to 1%, or from 0.01 to 0.5%, such as from 0.01 to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7. In particular, the tablet core has a friability of less than about 1.0%, optionally, less than about 0.5%, preferably less than about 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7 when the colesevelam is colsevelam hydrochloride. For example, the tablet core may have a friability of 0.001 to 1%, or from 0.01 to 0.5%, such as from 0.01 to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7 when the colesevelam is colsevelam hydrochloride.

[0212] The tablet core has a hardness of greater than about 70 N, optionally, greater than about 80 N, optionally, greater than about 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. In particular, the tablet core has a hardness of greater than about 70 N, optionally, greater than about 80 N, optionally, greater than about 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8 when the colesevelam is colsevelam hydrochloride.

[0213] The tablet core may have a hardness in the range of from 70 N to 450 N, such as from 80 N to 400 N, optionally from 90 N to 370 N, such as from 100 N to 330 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. In particular, the tablet core may have a hardness in the range of from 70 N to 450 N, such as from 80 N to 400 N, optionally from 90 N to 370 N, such as from 100 N to 330 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8 when the colesevelam is colsevelam hydrochloride.

[0214] For example, the tablet core may have a hardness in the range of from 70 N to 450 N, optionally, from 80 N to 450 N, optionally, from 90 N to 450 N, optionally from 100 N to 450 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Optionally, the tablet core may have a hardness in the range of from 70 N to 400 N, optionally, from 80 N to 400 N, optionally, from 90 N to 400 N, optionally from 100 N to 400 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Further optionally, the tablet core may have a hardness in the range of from 70 N to 370 N, optionally, from 80 N to 370 N, optionally, from 90 N to 370 N, optionally from 100 N to 370 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Further optionally, the tablet core may have a hardness in the range of from 70 N to 330 N, optionally,from 80 N to 330 N, optionally, from 90 N to 330 N, optionally from 100 N to 330 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8.

[0215] By way of further example, the tablet core may have a hardness in the range of from 70 N to 450 N, optionally, from 80 N to 450 N, optionally, from 90 N to 450 N, optionally from 100 N to 450 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8 when the colesevelam is colsevelam hydrochloride. Optionally, the tablet core may have a hardness in the range of from 70 N to 400 N, optionally, from 80 N to 400 N, optionally, from 90 N to 400 N, optionally from 100 N to 400 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8 when the colesevelam is colsevelam hydrochloride. Further optionally, the tablet core may have a hardness in the range of from 70 N to 370 N, optionally, from 80 N to 370 N, optionally, from 90 N to 370 N, optionally from 100 N to 370 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8 when the colesevelam is colsevelam hydrochloride. Further optionally, the tablet core may have a hardness in the range of from 70 N to 330 N, optionally, from 80 N to 330 N, optionally, from 90 N to 330 N, optionally from 100 N to 330 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8 when the colesevelam is colsevelam hydrochloride.

[0216] Suitably, in the unit dose pharmaceutical composition, the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and suitably, the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably in an amount of from 35 to 45 wt% of the tablet core. For example, the colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and suitably, the colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably in an amount of from 35 to 45 wt% of the tablet core.

[0217] Suitably, in the unit dose pharmaceutical composition, the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and suitably the total amount of colesevelam and / or pharmaceutically acceptable salts present in the unit dose pharmaceutical composition is present in an amount of at least 76 wt% of the tablet core, and suitably, the total amount of colesevelam and / or pharmaceuticallyacceptable salts thereof is present in an amount of from 700 mg to 1200 mg in the tablet core, preferably from 850 mg to 1100 mg in the tablet core, such as about 900 mg in the tablet core.

[0218] Suitably in the unit dose pharmaceutical composition, the colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and the colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and suitably the total amount of colesevelam hydrochloride present in the unit dose pharmaceutical composition is present in an amount of at least 76 wt% of the tablet core, and suitably, the total amount of colesevelam hydrochloride is present in an amount of from 700 mg to 1200 mg in the tablet core, preferably from 850 mg to 1100 mg in the tablet core, such as about 900 mg in the tablet core.

[0219] Suitably, the diluent is selected from one or more of mannitol, sucrose and cellulose, and is present in an amount of from 6 wt% to 18 wt% of the tablet core, and the binder is polyvinyl pyrrolidone and is present in an amount of from 2 wt% to 4 wt% of the tablet core.

[0220] Suitably, the colesevelam and / or pharmaceutically acceptable salt thereof is colesevelam hydrochloride.

[0221] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 400 mg to 1250 mg in the tablet core.

[0222] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core,wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrocholoride; and wherein the colesevelam hydrochloride is present in an amount of at least 70 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 400 mg to 1250 mg in the tablet core.

[0223] Suitably, the tablet core has a hardness of greater than about 70 N, optionally greater than about 80 N, optionally, greater than about 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. More suitably, the tablet core has a hardness in the range of from 70 N to 450 N, such as from 80 N to 400 N, optionally from 90 N to 370 N, such as from 100 N to 330 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of less than about 1%, optionally, less than about 0.5%, preferably less than about 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7. For example, the tablet core may have a friability of 0.001 to 1%, or from 0.01 to 0.5%, such as from 0.01 to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7. Suitably, the tablet core has the hardness and / or friability properties noted above when the colesevelam is colesevelam hydrochloride

[0224] For example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core; andcolesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 400 mg to 1250 mg in the tablet core; wherein the tablet core has a hardness of greater than about 70 N, optionally > greater than 80 N, optionally, > greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than about 1%, optionally, less than 0.5%, preferably less than 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0225] By way of further example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a nongranulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 70 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 400 mg to 1250 mg in the tablet core; wherein the tablet core has a hardness of greater than about 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than about 1%, optionally, less than 0.5%, preferably less than 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0226] For example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulatecomponent: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core, such as from 70 wt% to 90 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 400 mg to 1250 mg in the tablet core; wherein the tablet core has a hardness of greater than about 70 N, such as from 70 N to 450 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than about 1%, such as from 0.001 % to 1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0227] By way of further example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non- granulate component: wherein the granulate component comprises colesevelam hydrochloride thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 70 wt% of the tablet core, such as from 70 wt% to 90 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 400 mg to 1250 mg in the tablet core;wherein the tablet core has a hardness of greater than about 70 N, such as from 70 N to 450 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than about 1%, such as from 0.001 % to 1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0228] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 76 wt%, suitably at least 80 wt% more suitably at least 81 wt% of the tablet core, such as at least 82 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core.

[0229] Suitably, the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of less than 1.0%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0230] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder;wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 76 wt%, suitably at least 80 wt% more suitably at least 81 wt% of the tablet core, such as at least 82 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core.

[0231] Suitably, the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of less than 1.0%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0232] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount from 76 wt% to 90 wt%, suitably from 80 wt% to 90 wt%, more suitably from 81 wt% to 90 wt% of the tablet core, optionally, 82 wt% to 90 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core.

[0233] Suitably, the tablet core has a hardness of 70 N to 400 N, optionally 80 N to 400 N, optionally, 90 N to 400 N, such as 100 N to 400 N when measured in accordance with USPharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of 0.001% to 1%, optionally, 0.01 to 0.5%, preferably 0.1% to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0234] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount from 76 wt% to 90 wt%, suitably from 80 wt% to 90 wt%, more suitably from 81 wt% to 90 wt% of the tablet core, optionally, 82 wt% to 90 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core.

[0235] Suitably, the tablet core has a hardness of 70 N to 400 N, optionally 80 N to 400 N, optionally, 90 N to 400 N, such as 100 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of 0.001% to 1%, optionally, 0.01 to 0.5%, preferably 0.1% to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0236] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount from 81 wt% to 90 wt% of the tablet core, optionally, 82 wt% to 90 wt% of the tablet core;wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core.

[0237] Suitably, the tablet core has a hardness of 70 N to 400 N, optionally 80 N to 400 N, optionally, 90 N to 400 N, such as 100 N to 400 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of 0.001% to 1%, optionally, 0.01 to 0.5%, preferably 0.1% to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0238] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount from 81 wt% to 90 wt% of the tablet core, optionally, 82 wt% to 90 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core.

[0239] Suitably, the tablet core has a hardness of 70 N to 400 N, optionally 80 N to 400 N, optionally, 90 N to 400 N, such as 100 N to 400 N when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of 0.001% to 1%, optionally, 0.01 to 0.5%, preferably 0.1% to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0240] For example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 76 wt%, suitably at least 80 wt% more suitably at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0241] By way of further example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non- granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 76 wt%, suitably at least 80 wt% more suitably at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core; wherein colesevelam hydrochloride thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core;wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0242] For example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0243] By way of further example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0244] For example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of 76 wt% to 90 wt% of the tablet core, suitably from 80 wt% to 90 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core;wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0245] By way of example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of 76 wt% to 90 wt% of the tablet core, suitably from 80 wt% to 90 wt% of the tablet core,; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0246] For example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof ispresent in an amount of 81 wt% to 90 wt% of the tablet core, suitably from 82 wt% to 90 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0247] By way of further example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a nongranulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of 81 wt% to 90 wt% of the tablet core, suitably from 82 wt% to 90 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; andwherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0248] For example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 76 wt%, suitably at least 80 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0249] By way of further example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non- granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 76 wt%, suitably at least 80 wt% of the tablet core;wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0250] Also disclosed is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;Wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 81 wt% of the tablet core, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; andwherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0251] Also disclosed is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder;Wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 81 wt% of the tablet core, wherein colesevelam hydrochloride is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0252] Also disclosed is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;Wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 82 wt% of the tablet core, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; andcolesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0253] Also disclosed is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 82 wt% of the tablet core, wherein colesevelam hydrochloride is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0254] For example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coatingcovering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 76 wt% to 90 wt%, suitably from 80 wt% to 90 wt%; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0255] By way of further example, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non- granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of from 76 wt% to 90 wt%, suitably from 80 wt% to 90 wt%; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core;wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0256] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 81 wt% to 90 wt% of the tablet core, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0257] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet corecomprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of from 81 wt% to 90 wt% of the tablet core, wherein colesevelam hydrochloride is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0258] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 82 wt% to 90 wt% of the tablet core, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core;wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0259] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of from 82 wt% to 90 wt% of the tablet core, wherein colesevelam hydrochloride is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0260] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core;wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 400 mg to 1200 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0261] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 76 wt%, suitably at least 80 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer,copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0262] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 76 wt%, suitably at least 80 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0263] Disclosed herein is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core;wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0264] Disclosed herein is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer,copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0265] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;Wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of 76 wt% to 90 wt%, suitably from 80 wt% to 90 wt%, of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0266] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder;Wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of 76 wt% to 90 wt%, suitably from 80 wt% to 90 wt%, of the tablet core;wherein colesevelam hydrochloride is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0267] Provided herein is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;Wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of 81 wt% to 90 wt%, suitably from 82 wt% to 90 wt%, of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer,copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0268] Also provided herein is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder;Wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of 81 wt% to 90 wt%, suitably from 82 wt% to 90 wt%, of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 50 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 50 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0269] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core, suitably at least 75 wt% of the tabletcore, or 76 wt% of the tablet core more suitably at least 80 or at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0270] Suitably, the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0271] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 70 wt% of the tablet core, suitably at least 75 wt% of the tablet core, or 76 wt% of the tablet core more suitably at least 80 or at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; andcolesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose and a cellulose derivative , wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0272] Suitably, the tablet core has a hardness of greater than 70 N, optionally greater than 80 N, optionally, greater than 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of less than 1%, optionally, less than 0.5%, preferably less than 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0273] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 70 wt% to 90 wt% of the tablet core, suitably in an amount of from 75 wt% to 90 wt% of the tablet core, such as from 76 wt% to 90 wt% of the tablet core, more suitably from 80 wt% to 90 wt% of the tablet core, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core;wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers, such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0274] Suitably, the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0275] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of from 70 wt% to 90 wt% of the tablet core, suitably in an amount of from 75 wt% to 90 wt% of the tablet core, such as from 76 wt% to 90 wt% of the tablet core, more suitably from 80 wt% to 90 wt% of the tablet core, wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose and a cellulose derivative,wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; and wherein the non-granulate component comprises a lubricant and a glidant.

[0276] Suitably, the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8. Suitably, the tablet core has a friability of 0.001% to 1%, optionally, from 0.01% to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0277] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 76 wt%, suitably at least 80 wt%; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 6 to about 18 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate acacia gum and starch,preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant.

[0278] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 76 wt%, suitably at least 80 wt%; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 6 to about 18 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant.

[0279] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 81 wt%; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant.

[0280] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder;Wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 81 wt%; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core;wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant.

[0281] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;Wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 82 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant.

[0282] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder;Wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 82 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant.

[0283] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 70 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core; andcolesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 400 mg to 1200 mg in the tablet core, optionally from about 700 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt %, optionally from about 1 wt% to 4 wt% of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8, and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0284] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 76 wt% to 90 wt% of the tablet core, such as from 80 wt% to 90 wt% of the tablet core,; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core;wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 4 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8, and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0285] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of from 76 wt% to 90 wt% of the tablet core, such as from 80 wt% to 90 wt% of the tablet core,; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core;wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 4 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8, and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0286] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 81 wt% to 90 wt% of the tablet core, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core;wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 4 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8, and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0287] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of from 81 wt% to 90 wt% of the tablet core, wherein colesevelam hydrochloride is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 4 wt % of the tablet core;wherein the non-granulate component comprises a lubricant and a glidant; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8, and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0288] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 82 wt% to 90 wt% of the tablet core, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217>or with European Pharmacopoeia monograph 2.9.8, and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0289] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of from 82 wt% to 90 wt% of the tablet core, wherein colesevelam hydrochloride is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8, and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0290] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;Wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 400 mg to 1200 mg in the tablet core, optionally from about 700 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0291] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;Wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 76 wt%, suitably at least 80 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0292] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder;Wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 76 wt%, suitably at least 80 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core;wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0293] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;Wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 81 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core;wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0294] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder;Wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 81 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0295] The present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 82 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0296] The present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 82 wt% of the tablet core;wherein colesevelam hydrochloride is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0297] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of 76 wt% to 88 wt% of the tablet core, such as from 80 wt% to 88 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core;wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0298] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of 76 wt% to 88 wt% of the tablet core, such as from 80 wt% to 88 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer,copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0299] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of 81 wt% to 88 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0300] Also provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of 81 wt% to 88 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0301] Further provided is provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of 82 wt% to 88 wt% of the tablet core;wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0302] Further provided is provided is a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of 82 wt% to 88 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the (total) colesevelam hydrochloride (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core;wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; and wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide.

[0303] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 81 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the total colesevelam and / or pharmaceutically acceptable salts thereof in the unit dose is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch,preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide; wherein the tablet core has a hardness of greater than about 70 N, optionally greater than about 80 N, optionally, greater than about 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than about 1%, optionally, less than about 0.5%, preferably less than about 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0304] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 81 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the total colesevelam hydrochloride in the unit dose is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide;wherein the tablet core has a hardness of greater than about 70 N, optionally greater than about 80 N, optionally, greater than about 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than about 1%, optionally, less than about 0.5%, preferably less than about 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0305] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 82 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the total colesevelam and / or pharmaceutically acceptable salts thereof in the unit dose is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide; wherein the tablet core has a hardness of greater than about 70 N, optionally greater than about 80 N, optionally, greater than about 90 N, when measured in accordance with US Pharmacopeiamonograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than about 1%, optionally, less than about 0.5%, preferably less than about 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0306] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of at least 82 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the total colesevelam hydrochloride in the unit dose is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide; wherein the tablet core has a hardness of greater than about 70 N, optionally greater than about 80 N, optionally, greater than about 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of less than about 1%, optionally, less than about 0.5%, preferably less than about 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0307] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 81 wt% to 90 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the total colesevelam and / or pharmaceutically acceptable salts thereof in the unit dose is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide; wherein the tablet core has a hardness of 70 N to 450 N, optionally from 80 N to 400 N, optionally, from 90 N to 370 N, such as from 100 N to 330 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability from 0.001% to 1%, optionally, from 0.01% to 0.5%, such as from 0.01 to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0308] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core,wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of from 81 wt% to 90 wt% of the tablet core; wherein colesevelam hydrochloride is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the total colesevelam hydrochloride in the unit dose is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide; wherein the tablet core has a hardness of 70 N to 450 N, optionally from 80 N to 400 N, optionally, from 90 N to 370 N, such as from 100 N to 330 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability from 0.001% to 1%, optionally, from 0.01 % to 0.5%, such as from 0.01 to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0309] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder;wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof; and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 82 wt% to 90 wt% of the tablet core; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the total colesevelam and / or pharmaceutically acceptable salts thereof in the unit dose is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide; wherein the tablet core has a hardness of 70 N to 450 N, optionally from 80 N to 400 N, optionally, from 90 N to 370 N, such as from 100 N to 330 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability from 0.001% to 1%, optionally, from 0.01% to 0.5%, such as from 0.01 to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0310] Suitably, the present invention provides a unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride; and wherein the colesevelam hydrochloride is present in an amount of from 82 wt% to 90 wt% of the tablet core;wherein colesevelam hydrochloride is present in the granulate component in an amount of from 37 to 45 wt% of the tablet core; and colesevelam hydrochloride is present in the non-granulate component in an amount of from 37 to 45 wt% of the tablet core; wherein the total colesevelam hydrochloride in the unit dose is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein the diluent is selected from one or more of mannitol, sucrose, cellulose, and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl acohol; wherein the binder is present in an amount of from about 1 wt% to 5 wt % of the tablet core; wherein the non-granulate component comprises a lubricant and a glidant, wherein the lubricant comprises magnesium stearate; and wherein the glidant comprises colloidal silicon dioxide; wherein the tablet core has a hardness of 70 N to 450 N, optionally from 80 N to 400 N, optionally, from 90 N to 370 N, such as from 100 N to 330 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability from 0.001% to 1%, optionally, from 0.01% to 0.5%, such as from 0.01 to 0.1 % when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

[0311] In another aspect the present invention provides a method of manufacturing a unit dose pharmaceutical composition for oral administration comprising coating a tablet core as described herein with a gastro resistant coating.

[0312] For example, the present invention provides a method of manufacturing a unit dose pharmaceutical composition for oral administration comprising: coating a tablet core with a gastro resistant coating, wherein the tablet core comprises: a granulate component and a non-granulate component, wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder, wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof, and optionally, one or more of a diluent, a disintegrant, a glidant and a lubricant, andwherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 70 wt% of the tablet core.

[0313] The oral pharmaceutical compositions disclosed herein may release not more than about 50% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0314] The oral pharmaceutical compositions disclosed herein may release not more than about 45% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0315] The oral pharmaceutical compositions disclosed herein may release not more than about 40% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0316] The oral pharmaceutical compositions disclosed herein may release not more than about 35% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer(optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0317] The oral pharmaceutical compositions disclosed herein may release not more than about 30% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0318] The oral pharmaceutical compositions disclosed herein, may release not more than about 25% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0319] The oral pharmaceutical compositions disclosed herein, may release not more than about 20% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0320] The oral pharmaceutical compositions disclosed may release not more than about 50% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueousphosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0321] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 45% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0322] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 40% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0323] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 35% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0324] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 30% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or apharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0325] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 25% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0326] The oral pharmaceutical compositions disclosed herein, may release not more than about 20% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0327] Optionally, the oral pharmaceutical compositions disclosed herein releases not more than about 50% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0328] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 45% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP)dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0329] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 40% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0330] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 35% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0331] Suitably, the oral pharmaceutical compositions disclosed herein releases not more than about 30% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a United States Pharmacopeia (USP) dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0332] Suitably, any of the oral pharmaceutical compositions disclosed herein, may release not more than about 25% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0333] Suitably, the oral pharmaceutical compositions disclosed herein may release not more than about 20% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, and wherein the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0334] Optionally, the pharmaceutical composition releases not more than about 50% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0335] Optionally, the pharmaceutical composition releases not more than about 45% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0336] Optionally, the pharmaceutical composition releases not more than about 40% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0337] Optionally, the pharmaceutical composition releases not more than about 35% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0338] Optionally, the pharmaceutical composition releases not more than about 30% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0339] Optionally, the pharmaceutical composition releases not more than about 25% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0340] Optionally, the pharmaceutical composition releases not more than about 20% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 1 hour, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0341] Optionally, the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 2 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0342] Optionally, the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 3 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0343] Optionally, the pharmaceutical composition releases not less than about 80% of the amount of colesevelam, or a pharmaceutically acceptable salt thereof, when the pharmaceutical composition is placed in a USP dissolution apparatus II complying with USP <711> for 4 hours, wherein the dissolution apparatus comprises an aqueous phosphate buffer (optionally 1000 ml of said buffer) at pH 6.8 and at a temperature of 37 ± 0.5 °C, and wherein the aqueous solution is stirred at a rate of 100 rpm.

[0344] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 50% over about 1 hour, when measured at about pH 6.8.

[0345] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 45% over about 1 hour, when measured at about pH 6.8.

[0346] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 40% over about 1 hour, when measured at about pH 6.8.

[0347] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 35% over about 1 hour, when measured at about pH 6.8.

[0348] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 30% over about 1 hour, when measured at about pH 6.8.

[0349] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 25% over about 1 hour, when measured at about pH 6.8.

[0350] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate lower than about 20% over about 1 hour, when measured at about pH 6.8.

[0351] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate of greater than or equal to about 80% of colesevelam, or a pharmaceutically acceptable salt thereof, over about 2 hours, when measured at about pH 6.8.

[0352] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate of greater than or equal to about 80% of colesevelam, or a pharmaceutically acceptable salt thereof, over about 3 hours, when measured at about pH 6.8.

[0353] Optionally, the oral pharmaceutical compositions of the present invention have a dissolution rate of greater than or equal to about 80% of colesevelam, or a pharmaceutically acceptable salt thereof, over about 4 hours, when measured at about pH 6.8.

[0354] According to the invention, the dissolutions are measured with the with the USP dissolution apparatus type II equipped with a paddle at 100 rpm at 37°±2° C.

[0355] The oral pharmaceutical compositions of the present invention may have a dissolution rate of less than about 50% over about 1 hour and equal to or greater than about 80% over about 2 hours, when measured at about pH 6.8 with the USP dissolution apparatus type II equipped with a paddle at 100 rpm at 37°±2° C.

[0356] The oral pharmaceutical compositions of the present invention may have a dissolution rate of less than about 45% over about 1 hour and equal to or greater than about 80% over about 2 hours, when measured at about pH 6.8 with the USP dissolution apparatus type II equipped with a paddle at 100 rpm at 37°±2° C.

[0357] The oral pharmaceutical compositions of the present invention may have a dissolution rate of less than about 40% over about 1 hour and equal to or greater than about 80% over about 2 hours, when measured at about pH 6.8 with the USP dissolution apparatus type II equipped with a paddle at 100 rpm at 37°±2° C.

[0358] The oral pharmaceutical compositions of the present invention may have a dissolution rate of less than about 35% over about 1 hour and equal to or greater than about 80% over about 2 hours, when measured at about pH 6.8 with the USP dissolution apparatus type II equipped with a paddle at 100 rpm at 37°±2° C.

[0359] The oral pharmaceutical compositions of the present invention may have a dissolution rate of less than about 30% over about 1 hour and equal to or greater than about 80% over about 2 hours, when measured at about pH 6.8 with the USP dissolution apparatus type II equipped with a paddle at 100 rpm at 37°±2° C.

[0360] The colesevelam, or a pharmaceutically acceptable salt thereof, may be released in the ileum, thus ensuring release of the colesevelam or the salt thereof, where it is needed to maximize the treatment and the efficacy.

[0361] In another aspect the present invention provides a method of manufacturing a unit dose pharmaceutical composition for oral administration comprising the steps of:(i) providing a tablet core wherein the tablet core is a tablet core as described herein; and(ii) coating the tablet core with a gastro resistant coating and optionally a sub coating.

[0362] For example, the present invention provides a method of manufacturing a unit dose pharmaceutical composition for oral administration comprising the steps of:(i) providing a tablet core wherein the tablet core comprises:a granulate component and a non-granulate component, wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder, wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof, and optionally, one or more of a diluent, a disintegrant, a glidant and a lubricant, and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 66 wt% such as in an amount of at least 70 wt% of the tablet core; and(ii) coating the tablet core with a gastro resistant coating and optionally a sub coating.

[0363] The granulate component comprises granules comprising colesevelam and / or a pharmaceutically acceptable salt thereof, diluent, and a binder. The granulate is manufactured by granulation using a granulator.

[0364] The non-granulate component may comprise one or more of a diluent, a disintegrant, a glidant and a lubricant. For example, the non-granulate component may comprise two or more, or three or more, or all of a diluent, a disintegrant, a glidant and a lubricant.

[0365] Suitably, the non-granulate component comprises a diluent. Suitably, the non- granulate component comprises a disintegrant. Suitably, the non-granulate component comprises a glidant. Suitably, the non-granulate component comprises a lubricant. Optionally, the non-granulate component comprises a diluent and a disintegrant. Optionally, the non- granulate component comprises a diluent, a disintegrant and a glidant. Optionally, ...

Claims

Claims1. A unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof and optionally one or more of: a diluent, a disintegrant, a glidant and a lubricant; wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 66 wt% of the tablet core, such as at least about 70 wt% of the tablet core.

2. The unit dose pharmaceutical composition of claim 1 , wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 60 wt% of the tablet core, preferably 30 to 50 wt% of the tablet core, such as 35 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, optionally, in an amount of from 36 to 45 wt% of the tablet core, such as from 37 to 45 wt% of the tablet core.

3. The unit dose pharmaceutical composition of claim 1 or 2, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 30 to 60 wt% of the tablet core, preferably 30 to 50 wt% of the tablet core, such as 35 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, optionally, in an amount of from 36 to 45 wt% of the tablet core, such as from 37 to 45 wt% of the tablet core.

4. The unit dose pharmaceutical composition of any preceding claim, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of at least 76 wt% of the tablet core, preferably at least 80 wt% of the tablet core, more preferably at least 81 wt% of the tablet core, optionally at least 82 wt% of the tablet core.

5. The unit dose pharmaceutical composition of any preceding claim, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of from 400 mg to 1250mg in the tablet core, preferably in an amount of from 400 mg to 1200 mg in the tablet core, such as from 700 to 1200 mg in the tablet core, more preferably in an amount of from 850 mg to 1100 mg in the tablet core.

6. The unit dose pharmaceutical composition of any preceding claim, wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and wherein the colesevelam is present in the non-granulate component in an amount of from 30 to 50 wt% of the tablet core, more preferably 35 to 45 wt% of the tablet core, and wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in a total amount of at least 76 wt% of the tablet core, and wherein the colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of from 700 mg to 1200 mg in the tablet core, preferably from 850 mg to 1100 mg in the tablet core, such as about 900 mg in the tablet core.

7. The unit dose pharmaceutical composition of any preceding claim, wherein the tablet core has a friability of < 1.0%, optionally, < 0.5%, preferably < 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

8. The unit dose pharmaceutical composition of any preceding claim, wherein the tablet core has a hardness of > 70 N, optionally > 80 N, optionally, > 90 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8.

9. The unit dose pharmaceutical composition of any preceding claim, wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 76 wt% to 90 wt%, suitably from 80 wt% to 90 wt%; wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 35 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 35 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, such as in an amount of from 850 mg to 1100 mg in the tablet core;wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8; and wherein the tablet core has a friability of 0.001% to 1%, optionally, from 0.01 % to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

10. The unit dose pharmaceutical composition of any preceding claim, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in an amount of about 900 mg in the tablet core.

11. The unit dose pharmaceutical composition of any preceding claim, wherein the nongranulate component comprises one or more of a diluent, disintegrant, glidant and a lubricant; optionally, wherein the diluent is selected from one or more of polyols such as mannitol, lactose, sugars such as sucrose, dextrose, dextrates, sorbitol, fructose, inorganic salts such as dibasic and tribasic calcium phosphate, sodium chloride, starch, modified starch and derivatives thereof, cellulose, and a cellulose derivative (i.e. cellulose derivatives such as, for example, methyl, ethyl, or hydroxyethyl cellulose), and kaolin; further optionally, wherein the diluent is present in an amount of from 5 to 20 wt% of the tablet core, such as from 6 to 18 wt% of the tablet core, preferably from 7 to 16 wt% of the tablet core, more preferably from 10 to 15 wt% of the tablet core; optionally, wherein the binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol, copovidone, cellulose, and a cellulose derivative (e.g. hydroxypropyl cellulose, hypromellose, ethyl cellulose), acacia gum, starch, and a polymethylacrylate, preferably polyvinyl pyrrolidone and / or poly vinyl alcohol; further optionally, wherein the binder is present in an amount of from 1 wt% to 5 wt% of the tablet core, preferably from 2 wt % to 4 wt% of the tablet core; optionally, wherein the disintegrant is selected from one or more of sodium carboxy methyl cellulose, such as cross-linked sodium carboxy methyl cellulose, crospovidone, bentonite, an algin, a gum and modified starch, preferably, wherein the disintegrant is cross-linked sodium carboxy methyl cellulose, further optionally, wherein the disintegrant is present in an amount of from 0.1 wt% to 7 wt% of the tablet core, preferably from 0.5 wt % to 5 wt%, such as from 1 to 2.5 wt% of the tablet core, more preferably from 1 to 2 wt% of the tablet core.

12. The unit dose pharmaceutical composition of any preceding claim, wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of from 81 wt% to 90 wt% of the tablet core, wherein colesevelam and / or pharmaceutically acceptable salts thereof is present in the granulate component in an amount of from 36 to 45 wt% of the tablet core; and colesevelam and / or pharmaceutically acceptable salts thereof is present in the non-granulate component in an amount of from 36 to 45 wt% of the tablet core; wherein the (total) colesevelam and / or pharmaceutically acceptable salts thereof (in the unit dose) is present in an amount of from 700 mg to 1200 mg in the tablet core, optionally from about 850 to about 1100 mg in the tablet core; wherein said diluent is selected from one or more of mannitol, sucrose, cellulose and a cellulose derivative, wherein the diluent is present in an amount of from about 7 to about 16 wt% of the tablet core; wherein said binder is selected from one or more of polyvinyl pyrrolidone, polyvinyl alcohol and related graft copolymers such as polyvinyl alcohol graft polyethylene glycol copolymer, copovidone, cellulose, a cellulose derivative, a polymethacrylate, acacia gum and starch, preferably polyvinyl pyrrolidone and / or polyvinyl alcohol; wherein the binder is present in an amount of from about 1 wt% to 4 wt % of the tablet core; wherein the non-granulate component further comprises a lubricant and a glidant; wherein the tablet core has a hardness of 70 N to 400 N, optionally from 80 N to 400 N, optionally, from 90 N to 400 N, when measured in accordance with US Pharmacopeia monograph <1217> or with European Pharmacopoeia monograph 2.9.8, and wherein the tablet core has a friability of 0.001 % to 1%, optionally, from 0.01% to 0.5%, preferably from 0.01% to 0.1% when measured in accordance with US Pharmacopeia monograph <1216> or with European Pharmacopoeia monograph 2.9.7.

13. The unit dose pharmaceutical composition according to any preceding claim, wherein the gastro-resistant coating of the unit dose starts breaking or dissolving at or above a pH of 6.0, preferably at or above a pH of 6.5, more preferably at a pH of 6.8.

14. The unit dose pharmaceutical composition of any preceding claim, wherein the colesevelam and / or pharmaceutically acceptable salt thereof is colesevelam hydrochloride.

15. A method of manufacturing a unit dose pharmaceutical composition for oral administration comprising the steps of:(a) providing a tablet core wherein the tablet core comprises: a granulate component and a non-granulate component, wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder, wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof, and optionally, one or more of a diluent, a disintegrant, a glidant and a lubricant, and wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 66 wt% of the tablet core, preferably at least 70 wt% of the tablet core; and(b) coating the tablet core with a gastro resistant coating and optionally a sub-coating.

16. The method of claim 15, comprising the steps of:(i) combining colesevelam and / or pharmaceutically acceptable salts thereof, a diluent and a binder, to form a granulate;(ii) combining colesevelam and / or pharmaceutically acceptable salts thereof and, optionally, a diluent and a disintegrant, with the granulate of step (i), to form a tablet core having a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam and / or a pharmaceutically acceptable salt thereof, a diluent and a binder; wherein the non-granulate component comprises colesevelam or a pharmaceutically acceptable salt thereof, and, optionally, one or more of a diluent, a disintegrant, a glidant and a lubricant; wherein the colesevelam and / or the pharmaceutically acceptable salts thereof is present in an amount of at least 66 wt% of the tablet core, preferably at least 70 wt% of the tablet core; and(Hi) coating the tablet core with a gastro resistant coating and optionally a sub-coating; wherein optionally, step (i) involves wet granulation, further optionally,the wet granulation is carried out using water or a non-aqueous solvent, preferably a non-aqueous solvent, such as an organic solvent, such as an alcohol, preferably ethanol, a ketone or a chlorinated solvent.

17. The method of any one of claims 15 or 16, for bulk manufacture of a plurality of unit doses comprising a pharmaceutical composition for oral administration, wherein the plurality of unit doses has a deviation from the uniformity of mass of less than ±2%, preferably less than ±1%, more preferably less than ±0.8%.

18. A unit dose pharmaceutical composition for oral administration according to any one of claims 1 to 14 for use in a method of treating bile acid diarrhea, irritable bowel syndrome, optionally, irritable bowel syndrome subtype diarrhea (IBS-D), colitis, such as microscopic colitis, and / or bile acid malabsorption in a patient in need thereof, optionally, wherein the method comprises administering more than one of said unit dose oral pharmaceutical compositions to said patient.

19. A unit dose pharmaceutical composition for oral administration comprising a tablet core and a gastro-resistant coating covering the core, wherein the tablet core comprises a granulate component and a non-granulate component: wherein the granulate component comprises colesevelam hydrochloride, a diluent and a binder; wherein the non-granulate component comprises colesevelam hydrochloride and optionally one or more of: a diluent, a disintegrant, a glidant and a lubricant; wherein the colesevelam hydrochloride is present in an amount of about 66 wt% to about 90 wt% of the tablet core.

20. The unit dose pharmaceutical composition of claim 19, wherein colesevelam hydrochloride is present in the granulate component in an amount of from about 37 wt% to about 45 wt% of the tablet core; and / or wherein colesevelam hydrochloride is present in the non- granulate component in an amount of from about 37 wt% to about 45 wt% of the tablet core.

21. The unit dose pharmaceutical composition of claim 19 or 20, wherein colesevelam hydrochloride is present in an amount of from about 700 to about 1200 mg in the tablet core;suitably, wherein colesevelam hydrochloride is present in an amount of about 900 mg in the tablet core.

22. A method of treating bile acid diarrhea, irritable bowel syndrome, optionally, irritable bowel syndrome subtype diarrhea (IBS-D), colitis, such as microscopic colitis, and / or bile acid malabsorption in a patient in need thereof, wherein the method comprises administering a unit dose pharmaceutical composition according to any one of claims 1-14 to a patient in need thereof.

23. Use of a unit dose pharmaceutical composition according to any one of claims 1-14 in the manufacture of a medicament for treating bile acid diarrhea, irritable bowel syndrome, optionally, irritable bowel syndrome subtype diarrhea (IBS-D), colitis, such as microscopic colitis, and / or bile acid malabsorption.FRKelly

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