A stable capsule composition with gastro-resistant pellets for the treatment of iron deficiency anemia

Abstract

The present invention relates to provide a novel, long term stable gastro resistant capsule composition comprising ferrous glycine sulfate. The invention further relates to methods of using the pharmaceutical compositions to treat iron deficiency anemia and related disorders.

Description

[0001] A STABLE CAPSULE COMPOSITION WITH GASTRO-RESISTANT PELLETS FOR THE TREATMENT OF IRON DEFICIENCY ANEMIA

[0002] Technical field:

[0003] The present invention relates to develop a long term stable capsule composition with gastro- resistant pellets for treating iron deficiency. The developed composition comprises therapeutically effective amount of ferrous glycin sulfate and one or more enteric components for retention of the release in the stomach.

[0004] Prior Art:

[0005] Iron is a component of proteins required for crucial cellular processes. Iron-containing proteins have essential roles in oxygen transport, ATP production, DNA synthesis and other physiological processes. The content of iron in the body is about 50 mg of Fe2+ / kg body weight in men and about 38 mg of Fe2+ / kg body weight in women.

[0006] Worldwide, iron deficiency anemia is the most common nutritional deficiency (Clark, 2008). It is known that the deficiency of iron, an essential ingredient for hemoglobin synthesis in vivo, inhibits the formation of hemoglobin, and causes various anemic symptoms such as general malaise, headache, dizziness, sounding in the ears, pain at the glossal mucous membrane, reduced appetite, epigastralgia, etc. The causes of such iron deficiency include, for example, lack of iron up-take from foods, insufficiency of iron absorption due to abnormality or reduction of the function of the stomach and small intestine, increased demand for iron in vivo during the rapidly growing stage of infants or during-pregnancy, and unusually increased excretion of iron during menstruation or due to bleeding by peptic ulcer or other lesions. It is difficult to make up for such iron deficiency by foods alone because the ratio of iron absorbed by eating is very low and the amount of foods that can be taken is naturally limited. It is the general practice therefore to supply iron by orally or parenterally administering various iron-containing compounds as treating agents for the prevention and therapy of an iron deficiency syndrome.

[0007] Iron in a variety of forms is administered for the treatment of iron deficiency and related disorders as well as prophylactically to supply the minimum daily recommended allowance. A variety of iron compounds have been administered, including ferric and ferrous forms of elemental iron as salts, complexes, hydrates, chelates, and bound to polymer.

[0008] Iron salts include, but are not limited to, ferrous sulfate, ferrous gluconate, ferrous fumarate, ferric hypophosphite, ferric albuminate, ferric chloride, ferric citrate, ferric oxide saccharate, ferric ammonium citrate, ferrous chloride, ferrous iodide, ferrous lactate, ferric trisglycinate, ferrous bisglycinate, ferric nitrate, ferrous hydroxide saccharate, ferric sulfate, ferric gluconate, ferric aspartate, ferrous sulfate heptahydrate, ferrous phosphate, ferric ascorbate, ferrous formate, ferrous acetate, ferrous malate, ferrous glutamate, ferrous cholinisocitrate, ferroglycine sulfate, ferric oxide hydrate, ferric pyrophosphate soluble, ferric hydroxide saccharate, ferric manganese saccharate, ferric subsulfate, ferric ammonium sulfate, ferrous ammonium sulfate, ferrous ethylenediammonium sulfate tetrahydrate, ferric sesquichloride, ferric choline citrate, ferric manganese citrate, ferric quinine citrate, ferric sodium citrate, ferric sodium edetate, ferric formate, ferric ammonium oxalate, ferric potassium oxalate, ferric sodium oxalate, ferric peptionate, ferric manganese peptonate, ferric acetate, ferric fluoride, ferric phosphate, ferric pyrophosphate, ferrous pyrophosphate, ferrous carbonate saccharate, ferrous carbonate mass, ferrous succinate, ferrous citrate, ferrous tartrate, ferric fumarate, ferric succinate, ferrous hydroxide, ferrous nitrate, ferrous carbonate, ferric sodium pyrophosphate, ferric tartrate, ferric potassium tartrate, ferric subcarbonate, ferric glycerophosphate, ferric saccharate, ferric hydroxide saccharate, ferric manganese saccharate, ferrous ammonium sulfate, ferric sodium pyrophosphate, ferrous carbonate, ferric hydroxide, ferrous oxide, ferric oxyhydroxide, ferrous oxalate, and / or combinations thereof.

[0009] Iron chelates and complexes include, but are not limited to, ferric pyrophosphate, soluble ferric pyrophosphate, iron polysaccharide, iron bis glycinate, iron proteinate, methylidine-iron complex, EDTA-iron complex, phenanthrolene iron complex, p-toluidine iron complex, ferrous saccharate complex, ferrlecit, ferrous gluconate complex, ferrum Vitis, ferrous hydroxide saccharate complex, iron-arene sandwich complexes, acetylacetone iron complex salt, iron-dextran complex, irondextrin complex, iron-maltodextrin complex, iron-sorbitol-citric acid complex, saccharated iron oxide, ferrous fumarate complex, iron porphyrin complex, iron phtalocyamine complex, iron cyclam complex, dithiocarboxy-iron complex, desferrioxamine-iron complex, bleomycin-iron complex, ferrozine-iron complex, iron perhaloporphyrin complex, alkylenediamine-N,N'-disuccinic acid iron(lll) complex, hydroxypyridone-iron(lll) complex, aminoglyco side-iron complex, transferrin-iron complex, iron thiocyanate complex, iron complex cyanides, porphyrinato iron(lll) complex, polyamino polycarbonate iron complexes, dithiocarbamate iron complex, adriamycin iron complex, anthracycline-iron complex, MGD-iron complex, ferrioxamine B. ferrous citrate complex, ferrous sulfate complex, ferric gluconate complex, ferrous succinate complex, polyglucopyranosyl iron complex, polyaminodisuccinic acid iron complex, biliverdin-iron complex, deferiprone iron complex, ferric oxyhydride-dextran complex, dinitrosyl dithiolato iron complex, iron lactoferrin complexes, 1.3-PDTA ferric complex salts, diethylenetriaminepentaacetic acid iron complex salts, cyclohexane diaminetetraacetic acid iron complex salts, methyliminodiacetic acid iron complex salts, glycol etherdiaminetetraacetic acid iron complex salts, ferric hydroxypyrone complexes, ferric succinate complex, ferric chloride complex, ferric glycine sulfate complex, ferricaspartate complex, sodium ferrous gluconate complex, ferrous hydroxide polymaltose complex, and / or combinations thereof. WO 2005 / 041928 describes a composition comprising iron and a transport moiety, such as a fatty acid. The composition is prepared in a manner such that the iron and the transport moiety form a tight ion binding pair, i.e., a salt.

[0010] Some oral iron preparations available in the market have low bioavailability and substantial side effects associated with them. Numerous formulation attempts have been made to create dosage forms that provide adequate iron absorption to treat deficiencies with less side effects. The side effects from oral administration primarily are a result of the large doses necessary to promote adequate absorption. It is likely that the presence of unabsorbed iron that remains in the gastrointestinal (Gl) tract also significantly contributes to irritation, therefore side effects are also related to the poor bioavailability. The side effects include abdominal pain, heartburn, constipation, diarrhea, nausea and vomiting.

[0011] Although iron is extremely important, the iron overload and significant increase in iron stores can be toxic to the body. Scientists revealed that iron can increase lipid peroxidation and lead to cancer formation. The process of lipid peroxidation is initiated by reactive oxygen species, such as hydroxyl radicals, and stimulated by excess iron ions. On the other hand, iron-deficient rats rapidly accumulate copper eightfold higher than those in normal rats, and consequently, excess copper can also catalyze lipid peroxidation as iron. These challenges raise the need for a new composition that can secure the iron availability in the body through its high absorption rate, having ability to treat the iron-deficiency anemia in short time-course, and having high efficacy to overcome the life-threatening situation due to significantly low-Hb levels. There is a continuing need for development of novel pharmaceutical formulations of iron, suitable for oral administration, which not only offer the convenience of oral dosing but also provide increased bioavailability of iron without excessive side effects. In order to solve the mentioned problems, it is aimed to develop a new pharmaceutical composition using ferrous glycine sulfate as an iron source.

[0012] Niferex® G astro- resista nt Capsules, Ferro Sanol Duodenal® Capsules and Gyno Ferro Sanol® comprising ferrous glycine sulfate in an amount corresponding to ferrous (ll)-glycine-sulphate complex 567.7 mg (equivalent to 497.9 mg of ferrous II) (equivalent to 100 mg Fe2+). Accordingly, inventors of the present invention have developed compositions of ferrous glycine sulfate capsules containing g astro- resista nt pellets that were found to be comparable with marketed Niferex® Gastro-resistant Capsules (Aesica Pharmaceuticals GmbH).

[0013] Ferrous glycine sulphate (generic names as ferroglycine sulfate, ferroglycinsulfat, ferrous aminoacetosulphate can be used interchangeable) is an antianemic agent indicated in the treatment of iron deficiency and iron deficiency anemia. Its molecular formula is C2H5FeNOeS and molecular weight is 226.97 g / mol. Ferrous glycine sulphate is a complex produced with starting materials of ferrous sulphate heptahydrate and glycine. It is slightly soluble in water, practically insoluble in most of the organic solvents like acetone, ethanol, and propanol. Clinical studies show that, substitution with the highly bioavailable ferrous glycine sulfate complex compensates for the deficiency.

[0014] Some immediate release iron-containing drugs have undesirable side effects on the gastric mucosa. These have the defect of stimulating the mucous membrane of the stomach and being likely to cause a serious gastric trouble. Since it is common that continued administration over several months is required for the treatment of iron deficiency, the aforesaid defect sets a marked restriction on the use of inorganic ferrous salts as treating agents for iron deficiency. Therefore, it is preferable to design oral modified-release formulations in order to improve tolerability and adherence to treatment.

[0015] Iron is taken up by a special iron transporting system into the absorptive cells of the duodenum and upper small intestine, and is transported either directly into the plasma or is stored as mucosal ferritin. Absorption appears to be regulated by a single hematopoietic transcription factor (NF-E2), which links intestinal transport to erythropoiesis. Hard capsules contain gastro-resistant granules and the capsule shell dissolves in the stomach. The granules remain intact until they are released into the duodenum and the active ingredient ferrous glycine sulphate is rapidly released. In subjects with depleted iron stores the relative bioavailability is 95% that of an aqueous iron sulphate solution as reference. This corresponds to a Fe2+absorption in the range of 15 % for the 100 mg capsule.

[0016] As a result of the aforementioned issues, there is a need for development of novel pharmaceutical formulations of iron suitable for oral administration, which not only offer the convenience of oral dosing, but also provide increased bioavailability of iron without excessive side effects. Such a formulation allows therapeutic doses to be given by a non-parenteral route while providing decreased side effects compared to present formulations. Such an improved formulation can be used to replace parenteral therapy, and further improve patient quality of life.

[0017] Description of the Invention:

[0018] The present invention relates to pharmaceutical compositions and oral dosage forms of iron enhancing bioavailability of iron without excessive side effects which is used for treating iron deficiency.

[0019] It is an object of the present invention to provide a novel oral pharmaceutical capsule compositions containing gastro-resistant pellets which are comprising ferrous glycine sulfate as an iron source.

[0020] The present invention relates to develop a pharmaceutical composition suitable for oral administration of ferrous glycine sulfate, which composition exhibits enhanced in-vitro release at shelf-life and improved stabiliy upon accelerated storage.

[0021] The present invention relates to develop a pharmaceutical capsule containing gastro-resistant pellets composition having improved storage stability comprising therapeutically effective amount of ferrous glycine sulfate and one or more enteric components for retention of the release in the stomach, wherein the said pellets coated with 1 1 .5 % - 14.5 % (w / w) enteric coating.

[0022] The present invention relates to develop a pharmaceutical capsule containing g astro- resista nt pellets composition having improved storage stability comprising therapeutically effective amount of ferrous glycine sulfate and one or more enteric components for retention of the release in the stomach, wherein the said pellets coated with 12 % - 14 % (w / w) enteric coating.

[0023] The present invention relates to develop a pharmaceutical capsule containing g astro- resista nt pellets composition having improved storage stability comprising therapeutically effective amount of ferrous glycine sulfate and one or more enteric components for retention of the release in the stomach, wherein the said pellets coated with 12 % - 14 % (w / w) enteric coating comprising polymethacrylate polymers.

[0024] The present invention relates to develop a pharmaceutical capsule containing g astro- resista nt pellets composition having improved storage stability comprising therapeutically effective amount of ferrous glycine sulfate and one or more enteric components for retention of the release in the stomach, wherein the said pellets coated with 12 % - 14 % (w / w) enteric coating comprising Eudragit.

[0025] The present invention relates to develop a pharmaceutical capsule comprising therapeutically effective amount of ferrous glycine sulfate, and one or more enteric components for retention of the release in the stomach as well as a gastro-resistant pellets composition, the capsule may further comprises folic acid and vitamin B12, wherein the said pellets coated with 12 % - 14 % (w / w) enteric coating comprising Eudragit.

[0026] In recent years, a continuous interest has been focused on the development of controlled drug release formulations using multiparticulate systems (e.g., pellets), offering various advantages over single dosage forms, namely, an improved bioavailability and easy administration for elderly people and for children. These include a low risk of dose dumping, flexibility of blending units with different release patterns, reproducible gastric residence time, and prevention of high local drug concentration in the gastrointestinal tract.

[0027] Ferrous glycine sulfate can be useful in iron deficiency anemia associated with autoimmune gastritis or Heliobacter pylori gastritis and having less gastrointestinal side-effects than standard preparations such as iron fumarate.

[0028] The term "active ingredient" or "active pharmaceutical ingredient" means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. In the present invention, the active ingredient is iron salt of ferrous glycine sulphate. The term “therapeutically effective amount” refers to the amount of iron or its pharmaceutically acceptable salts, esters, and solvates thereof, that is an amount sufficient to effect treatment, as defined herein, when administered to a subject in need of such treatment. In the present invention each capsule contains 567.7 mg (equivalent to 497.9 mg of ferrous II) ferrous (ll)-glycine-sulphate complex (equivalent to 100 mg Fe2+).

[0029] As used herein, “stable” refers to a composition that substantially maintains its physical and chemical properties when stored. A pharmaceutical composition comprising an active ingredient is considered to be "stable" if said ingredient degrades less or more slowly than it does on its own and / or in known pharmaceutical compositions and maintain the in-vitro dissolution profile upon the stability process.

[0030] The term "improved properties" encompasses the advantages of the finished product obtained from the formulation obtained with the present invention. These advantages include, in particular, the improvement of in-vitro release and obtaining a more stable product, especially under accelerated stability conditions in long term. In the present invention, the compositions developed in this present invention was compared with the Niferex® Capsule, and consecuently it was concluded to have improved stability relative to their in-vitro release at long term stability conditions.

[0031] The term "formulation" refers to granules and / or solid oral pharmaceutical dosage forms of the invention that contain ferrous glycine sulphate and one or more enteric components.

[0032] An "enteric coating" is a substance that remains substantially intact in the stomach but dissolves and releases the drug in the small intestine and / or colon. Generally, the enteric coating comprises a polymeric material that prevents release in the low pH environment of the stomach but that ionizes or solubilizes at a higher pH, typically a pH of 5 to 7, but at least above 3.0, more or above 5, or even more specifically at a pH of about 5.5 to about 7, and thus dissolves sufficiently in the small intestine and / or colon to release the active agent therein. The enteric coating material should be non-toxic and is predominantly soluble in the intestinal fluid, but substantially insoluble in the gastric fluids.

[0033] The pharmaceutical compositions and oral dosage forms of the invention can comprise one or more auxiliary excipients, such as for example rate-controlling polymeric materials, solubilizers, diluents, lubricants, disintegrants, plasticizers, anti-tack agents, opacifying agents, glidants, pigments, flavorings, and the like.

[0034] The term “rate controlling polymer” material as used herein includes hydrophilic polymers, hydrophobic polymers and mixtures of hydrophilic and / or hydrophobic polymers that are capable of controlling or retarding the release of the peptide or protein from a solid oral dosage form of the present invention. Suitable rate controlling polymer materials include those selected from the group consisting of hydroxyalkyl cellulose such as hydroxypropyl cellulose and hydroxypropyl methyl cellulose; poly(ethylene) oxide; alkyl cellulose such as ethyl cellulose and methyl cellulose; carboxymethyl cellulose; hydrophilic cellulose derivatives; polyethylene glycol; polyvinylpyrrolidone; cellulose acetate; cellulose acetate butyrate; cellulose acetate phthalate; cellulose acetate trimellitate; polyvinyl acetate phthalate; hydroxypropylmethyl cellulose phthalate; hydroxypropylmethyl cellulose acetate succinate; polyvinyl acetaldiethylamino acetate; poly(alkylmethacrylate) and poly(vinyl acetate). Other suitable hydrophobic polymers include polymers and / or copolymers derived from acrylic or methacrylic acid and their respective esters, Zein, waxes, shellac and hydrogenated vegetable oils. Particularly useful in the practice of the present invention are poly acrylic acid, poly acrylate, poly methacrylic acid and poly methacrylate polymers such as those sold under the Eudragit tradename (Rohm GmbH, Darmstadt, Germany) specifically Eudragit(R) L, Eudragit(R) S, Eudragit(R) RL, and Eudragit(R) RS coating materials and mixtures thereof. Some of these polymers can be used as delayed release polymers to control the site where the drug is released. They include polymethacrylate polymers such as those sold under the Eudragit tradename (Rohm GmbH, Darmstadt, Germany).

[0035] The following examples represent various embodiments of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope of the invention.

[0036] Example 1. Production Methods

[0037] In the formulation, the reference product produced by Minapharm under the trademark Niferex® G astro- resista nt Capsules (Aesica Pharmaceuticals GmbH) was referenced. The formulation development studies started with the investigation of the physical properties, chemical properties, solubility and pharmacokinetic properties of the active ingredients. The properties of the finished product were determined by taking into account the content, in-vitro release of the formulation of the reference product.

[0038] The pellets comprising ferrous glisin sulfate, when the product temperature reaches 30-32°C, were coated with enteric coating solution. The enteric coating solution comprises Eudragit L30, triethyl citrate, talc and water.

[0039] In the sustained release ferrous glycine sulfate capsules containing gastro-resistant pellets, the enteric coating percentage that controls the release is a critical parameter. Since the most important criterion in the present composition is the percentage of enteric coating used, different coating percentages of enteric coating were applied to the prepared pellets. Table 1. Formulations containing different amounts of enteric coating

[0040] Enteric Coating %

[0041] Formulation-1 11 %

[0042] Formulation-2 12%

[0043] Formulation-3 14%

[0044] Formulation-4 15%

[0045] Formulation-5 18%

[0046] Example 2. Dissolution Profiles

[0047] Dissolution testing of the capsules was performed using USP Apparatus I (basket) at 100 rpm starting with 900 mL solution at 37±0.5 °C. The preparation method of the dissolution medium was as follows. Firstly, capsules were placed in a 0.1 M HCI solution for 120 min and samples were collected every 60 minutes repeated to 120 minutes. At the end of the acid stage dissolution, capsules were transferred to the buffer stage. The buffer stage is 900 ml dissolution medium in pH 6.0 sodium acetate buffer with 2.0% ascorbic acid at 100 rpm. At the end of 60 minutes, samples were collected from each of the vessel The samples were analyzed at 523 nm (UV / VIS Spectrophotometer). The amount of iron released from each capsule was evaluated over a 3- hour period, using the Distek Dissolution Instrument.

[0048] The percentage of dissolved iron for each capsule at each time point was calculated as a cumulative frequency, using the percentage of dissolved iron at all time points that had been analyzed up to that point. For each time point, the mean percentage of dissolved iron was calculated from the six capsules, together with the relative standard deviation. The mean values were plotted in dissolution curves for the two products under evaluation and allowed comparison by means of the similarity factor, f2 (Eq. 1). An f2 value of between 50 and 100 suggests that the two dissolution profiles are similar.

[0049] Iron release from the capsule is not expected in in-vitro dissolution studies performed in acid medium (acceptance criterion; maximum of 10% after 120 minutes). Both the test products and the reference product released a maximum of 3% in the acid stage. On the other hand, in-vitro releases in buffer stage are affected by enteric coating percentages. The results are summarized in Table 2 below. Table 2. Comparison of formulations containing different amounts of enteric coating with Niferex® Capsules at buffer stage (pH 6.0 Sodium Acetate Buffer with 2.0% ascorbic acid) after 60 minutes

[0050] Release % Iron

[0051] _ T.ime Niferex®

[0052] C _apsu .les

[0053] Formulation-1 Formulation-2 Formulation-3 Formulation-4 Formulation-5

[0054] 10 min 51 66 36 38 26 8.8

[0055] 15 min 70 94 65 65 51 33

[0056] 30 min 95 98 99 99 88 90

[0057] 45 min 98 98 99 99 100 98

[0058] 60 min 100 98 99 99 100 98 f246 59 61 44 32

[0059] Example 3. Stability Studies

[0060] The stability of a drug substance is an important factor in the manufacture of safe and effective pharmaceutical products. Stability studies are required to be submitted by any applicant seeking approval for a new pharmaceutical product. Stability study requirements are covered, for example in the United States Pharmacopea, in the Good Manufacturing Practices (GMP) as well as in FDA and ICH Guidelines. Stability issues can be caused by environmental factors such as humidity, temperature and the like. The physical and chemical stability may be tested in conventional manner.

[0061] Physical stability means that the formulation is totally unchanged throughout its shelf-life and has not suffered any changes by way of appearance, organoleptic properties (color, odor and taste), hardness, brittleness etc. Also, physical stability affects pharmaceutical elegance, drug content uniformity and drug release rate. The general appearance of a capsule, its visual identity and overall elegance is essential for consumer acceptance and lot-to-lot uniformity, general capsule- to-capsule uniformity, and for monitoring trouble free manufacturing. The control of general appearance of capsules involves the measurements of a number of capsule’s size, shape, color, presence or absence of an odor, taste, surface texture, physical flaws and consistency, and legibility of any identifying markings.

[0062] In order to examine the physical and chemical stability of the products, stability test was assessed under accelerated condition (40°C±2°C, 75% Relative humidity, RH±5%) and ambient temperature condition (25°C±2°C / 60±5% Relative Humidity, RH±5%) for Test products (Formulation 2 and Formulation 3) and Reference Products (Niferex® Gastro-resistant Capsules) according to ICH Stability Testing of New Drug Substances And Products Q1 A(R2) Guidelines. The products were tested for content and dissolution of iron from capsules containing gastro- resistant pellets at acid and buffer medium conditions in regular intervals. Determination of content was performed with a validated UV-VIS Spectrophotometer method at 523 nm. The determination of in-vitro iron release from capsules containing gastro resistant pellets was performed with a validated UV-VIS method at 523 nm for acid and buffer stages.

[0063] It is known that the successful treatment of the acute episode acidosis due to various causes as well as the prevention of recurrency with capsules containing gastro-resistant pellets comprising ferrous glycine sulphate require a defined release profile of ferrous glycine sulphate from the dosage form. Since the criterion for stability of an capsules containing gastro-resistant pellets dosage form is that it should not release a significant amount of the active ingredient in the stomach, but should dissolve in the higher pH environment of the intestine. In vitro dissolution stability is monitored in 0.1 N hydrochloric acid as an acid stage, and pH 6.0 sodium acetate buffer with 2.0% ascorbic acid as an buffer stage. The USP standards for capsules containing gastro- resistant pellets entails stability testing of the products at elevated temperatures for extended periods of time.

[0064] Table 3. Comparison of in-vitro dissolution results of compositions containing different amounts of enteric coating and Niferex® Gastro-resistant Capsules (Aesica Pharmaceuticals GmbH) initially and after stability conditions at buffer stage (pH 6.0 Sodium Acetate Buffer with 2.0% ascorbic acid) after 60 minutes

[0065] Release % Ferrous

[0066] After 1 After 3 months After 6 months After 12 initiaHy month months

[0067] Capsules

[0068] Formulation-2 99 98 99 99 100 98 98

[0069] Formulation-3 97 98 99 101 99 98 99

Claims

CLAIMS1 . A pharmaceutical capsule containing gastro-resistant pellets composition having improved storage stability comprising therapeutically effective amount of ferrous glycine sulfate and one or more enteric components for retention of the release in the stomach, wherein the said pellets coated with 11 .5 % - 14.5 % (w / w) enteric coating.

2. The pharmaceutical composition according to claim 1 , wherein the said pellets coated with 12 % - 14 % (w / w) enteric coating.

3. The pharmaceutical composition according to claim 1 , wherein the enteric coating comprises polymethacrylate polymers.

4. The pharmaceutical composition according to claim 3, wherein the enteric coating comprises Eudragit.

5. The pharmaceutical composition according to claim 1 , wherein each capsule contains 567.7 mg (equivalent to 497.9 mg of ferrous II) ferrous (ll)-glycine-sulphate complex (equivalent to 100 mg Fe2+).

6. The pharmaceutical composition according to claim 1 , wherein the said composition may further comprise folic acid and vitamin B12.

7. The pharmaceutical composition according to claim 1 , wherein the said composition is used for treating iron deficiency.

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