Encapsulated medium chain fatty acid salts and oral solid dosage forms derived therefrom

Abstract

An encapsulated medium chain fatty acid salt in the form of core-shell, wherein (i) the core comprises at least one alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt; and (ii) the shell comprises at least one alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt encapsulating the core, is disclosed in the present disclosure. Also disclosed is the use of such encapsulated acids in pharmaceutical compositions, particularly in oral solid dosage forms such as tablets. The tablets according to the present disclosure having excellent mechanical properties.

Description

ENCAPSULATED MEDIUM CHAIN FATTY ACID SALTS AND ORAL SOLID DOSAGE FORMS DERIVED THEREFROMFIELD OF THE INVENTION

[0001] The presently disclosed process(es), procedure(s), method(s), product(s), result(s), and / or concept(s) (collectively referred to hereinafter as the “present disclosure”) relates generally to an encapsulated medium chain fatty acid salt(s) in the form of core-shell and a process(es) for preparation thereof. The present disclosure also relates to an oral solid dosage composition(s) comprising the encapsulated medium chain fatty acid salt(s) and a process(es) for preparation thereof.BACKGROUND OF THE INVENTION

[0002] Tablets and capsules represent the most preferred and most commonly dispensed pharmaceutical dosage forms for administering active pharmaceutical ingredients (APIs). The manufacturing of tablets can occur through direct compression or various granulation techniques such as dry, wet or melt granulation of drug(s) / excipient(s) mixtures. The choice of tableting process is highly influenced by the flowability and compressibility of tableting mixture, for example, API-excipients mixture. Two major factors which disparagingly affect the direct compression process are: compressibility and flowability of the tableting mixture. Direct compression method demands excellent flowability and compression of the tableting mixture. Most of the commercially available excipients fail to meet the desired set of functionalities as they often conflict with each other. Increasing compressibility can decrease flowability, making it challenging to find excipients that can fulfill the necessary criteria effectively. Many commercially available excipients struggle to meet these demands, highlighting the complexities of formulating effective tablets.

[0003] Salts of medium chain fatty acids are highly water-soluble excipients offering several advantages in tablet coatings such as improved solubility, oxidative stability and the like. However, these excipients are also allied with certain disadvantages such as dust powder generation, cohesiveness, low bulk density, poor bonding properties. Additionally, their soft and waxy nature hinders effective tablet formation and compromises permeation capabilities of tablets.To provide tablets with enhanced permeation capability, the medium chain fatty acids are typically used in high dosage forms which adversely affect the tablet formation.

[0004] Therefore, there is a long-felt need in the art to develop improved medium chain fatty acid salts having superior flow properties and compaction behavior, and their use in the preparation of oral solid dosage forms of proteins, peptides, BCS class II and BCS class IV poor soluble drugs.SUMMARY OF THE INVENTION

[0005] In one aspect of the present disclosure, there is provided an encapsulated medium chain fatty acid salt in the form of core-shell, wherein (i) the core comprises at least one alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt; and (ii) the shell comprises at least one alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt encapsulating the core. In one nonlimiting embodiment of the present disclosure, the alkali metal salts of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salts, present in the core and shell, are the same. In non-limiting embodiment of the present disclosure, the medium chain fatty acid includes at least one saturated fatty acid comprising 6 to 18 carbon atoms. In one non-limiting embodiment of the present disclosure, the medium chain fatty acid is selected from the group consisting of caproic acid, heptanoic acid, caprylic acid, nonanoic acid, capric acid, undecanoic acid, lauric acid, myristic acid, palmitic acid, and stearic acid. In one non-limiting embodiment of the present disclosure, the alkali metal includes at least one metal selected from sodium, potassium, calcium, or magnesium.

[0006] In one non-limiting embodiment of the present disclosure, the encapsulated medium chain fatty acid salt (core-shell) is in the form of particles having a particle size (d50) in the range of 150 pm to 350 pm. In another non-limiting embodiment of the present disclosure, the particles are obtained through a wet granulation process selected from a fluidized bed granulation, or high shear granulation, or low shear granulation, or melt granulation process, or foam granulation.

[0007] Another aspect, the present disclosure provides a process for preparing the encapsulated medium chain fatty acid salts in the form of core-shell, wherein the process comprising the steps of: preparing a supersaturated aqueous solution of alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt by dissolving at least one first alkali metal salt of medium chain fatty acid or first sodium salcaprozate functionalized medium chain fatty acid salt in distilled water at a temperature in the range of from 50 °C to 60 °C and under continuous stirring; ii. introducing at least one second alkali metal salt of medium chain fatty acid or second sodium salcaprozate functionalized medium chain fatty acid salt in a fluidized bed dryer for preparing the core; and iii. spraying the supersaturated solution of process step (i) onto the resultant of process step (ii) to form a shell encapsulating the core. In one non-limiting embodiment of the present disclosure, the first and the second alkali metal salts of medium chainfatty acid, or the first and the second sodium salcaprozate functionalized medium chain fatty acid salts are the same.

[0008] In a still another aspect, the present disclosure provides an oral solid dosage composition comprising: (i) the encapsulated medium chain fatty acid salt of the present disclosure; (ii) at least one active pharmaceutical ingredient or active nutraceutical ingredient; and (iii) at least one pharmaceutically acceptable excipient or nutraceutically acceptable excipient.

[0009] In one non-limiting embodiment of the present disclosure, the oral solid dosage composition includes a tablet, a minitablet, a capsule, powder, granules, sachets, or lozenges. In one non-limiting embodiment of the present disclosure, the oral solid dosage form is a tablet. In one non-limiting embodiment of the present disclosure, the tablet is an immediate release tablet, a modified release tablet, a controlled release tablet, a sustained release tablet, or an extended-release tablet.

[0010] In yet another aspect, the present disclosure provides a tablet composition comprising: (i) the encapsulated medium chain fatty acid salt of the present disclosure; (ii) at least one active pharmaceutical ingredient; and (iii) at least one pharmaceutically acceptable excipient. In one nonlimiting embodiment of the present disclosure, the active pharmaceutical ingredient is selected from the group consisting of proteins, peptides including macrocyclic peptides, and poor soluble drugs of BCS class II and BCS class IV. In one non-limiting embodiment of the present disclosure, the pharmaceutically acceptable excipient is selected from the group consisting of fillers, binders, disintegrating agents, lubricants, flow aids, and any combinations thereof.

[0011] Another aspect of the present disclosure provides a process for preparing the tablet composition of present disclosure, where the process comprising the steps of: i. blending the active pharmaceutical ingredient, the encapsulated medium chain fatty acid salt of the present disclosure, and one or more pharmaceutically acceptable excipient; and ii. compressing the components of step (i) to obtain the tablet composition.BRIEF DESCRIPTION OF THE FIGURES AND DRAWINGS

[0012] Objects, features, and advantages of the present disclosure will become apparent upon reading the following description in conjunction with the drawings / figures, in which:

[0013] FIG. 1 illustrates the hardness (kp) of the tablet samples of Ex.1 and its comparison with tablets prepared from commercial samples of sodium caprate (commercial sodium caprate 1 and commercial sodium caprate 2).

[0014] FIG. 2 illustrates the hardness (kp) of the tablet samples of Ex.3 and its comparison with tablets prepared from commercial samples of sodium caprate (commercial sodium caprate 1 and commercial sodium caprate 2).

[0015] FIG 3. illustrates the tabletability profile of tablet samples of Ex. 3

[0016] FIG. 4 illustrates the hardness (kp) of the tablet samples of Ex.5 and its comparison with tablets prepared from commercial sodium caprylate sample 1 and commercial sodium caprylate Sample 2DETAILED DESCRIPTION OF THE INVENTION

[0017] Before explaining at least one embodiment of the inventive concept(s) in detail by way of exemplary drawings, experimentation, results, and laboratory procedures, it is to be understood that the inventive concept(s) is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings, experimentation and / or results. The inventive concept(s) is / are capable of other embodiments or of being practiced or carried out in various ways. As such, the language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are meant to be exemplary - not exhaustive. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

[0018] Unless otherwise defined herein, scientific, and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art.

[0019] All patents, published patent applications, and non-patent publications mentioned in the specification are indicative of the level of skill of those skilled in the art to which this present disclosure pertains. All patents, published patent applications, and non-patent publications referenced in any portion of this application are herein expressly incorporated by reference in their entirety to the same extent as if each individual patent or publication was specifically and individually indicated to be incorporated by reference.

[0020] All of the compositions and / or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and / or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the inventive concept(s) as defined by the appended claims.

[0021] As utilized in accordance with the present disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

[0022] The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and / or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” The use of the term “or” in the claims is used to mean “and / or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and / or.” Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, and / or the variation that exists among the study subjects. The use of the term “at least one of X, Y and Z” will be understood to include X alone, Y alone, and Z alone, as well as any combinations ofX, Y and Z.

[0023] As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open- ended and do not exclude additional, unrecited elements or method steps.

[0024] The term “or combinations thereof’ as used herein refers to all permutations and combinations of the listed items preceding the term. For example, “A, B, C, or combinations thereof’ is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.

[0025] The term “each independently selected from the group consisting of’ means when a group appears more than once in a structure, that group may be selected independently each time it appears.

[0026] In one aspect, the present disclosure provides an encapsulated medium chain fatty acid salt in the form of core-shell, wherein (i) the core comprises at least one alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt; and (ii) the shell comprises at least one alkali metal salt of medium chain fatty acid or sodium salcaprozatefunctionalized medium chain fatty acid salt encapsulating the core. The alkali metal salt of medium chain fatty acids salts or the sodium salcaprozate functionalized medium chain fatty acid salt, present in the core and shell of the present encapsulated medium chain fatty acid salts, are the same.

[0027] In one non-limiting embodiment of the present disclosure, the medium chain fatty acid salt can be alkali metal salt of medium chain fatty acids. Further, the medium chain fatty acids according to the present disclosure include at least one saturated fatty acid comprising 6 to 18 carbon atoms. In one non-limiting embodiment of the present disclosure, the medium chain fatty acid can be selected from the group consisting of caproic acid, heptanoic acid, caprylic acid, nonanoic acid, capric acid, undecanoic acid, lauric acid, myristic acid, palmitic acid, and stearic acid.

[0028] In one non-limiting embodiment of the present disclosure, the alkali metal can include at least one metal selected from the group consisting of sodium, potassium, calcium, and magnesium. In one non-limiting embodiment of the present disclosure, the alkali metal salt of medium chain fatty acid can be selected from the group consisting of sodium caprate, sodium caprylate, and sodium laurate.

[0029] In one non-limiting embodiment of the present disclosure, the weight ratio between the alkali metal salt of medium chain fatty acid core and the alkali metal salt of medium chain fatty acid shell varies in the range of from about 1 : 5 to about 5 : 1.

[0030] The encapsulated medium chain fatty acid salt (core-shell) according to the present disclosure is in the form of particles having a particle size (d50) in the range of from about 150 pm to about 350 pm. Further, the encapsulated medium chain fatty acid salt particles according to the present disclosure are characterized with Flowdex flowability index in the range of from about 10 mm to about 20 mm, flow function coefficient (ffc) ranging from 4 to 10, and an aspect ratio, measured using Malvern Morphologi G3S, in the range of from 0.5 to 1.0.

[0031] In one non-limiting embodiment of the present disclosure, the particle size can vary in the range of from about 150 pm to about 175 pm, or from about 175 pm to about 200 pm, or from about 200 pm to about 225 pm, or from about 225 pm to about 250 pm, or from about 250 pm to about 275 pm, or from about 275 pm to about 300 pm, or from about 300 pm to about 350 pm. In another non-limiting embodiment of the present disclosure, the Flowdex flowability index canvary in the range of from about 10 mm to about 1 1 mm, or from about 11 mm to about 12 mm, or from about 12 mm to about 13 mm, or from about 14 mm to about 15 mm, or from about 16 mm to about 17 mm, or from about 18 mm to about 19 mm, or from about 19 mm to about 20 mm. In another non-limiting embodiment of the present disclosure, the flow function coefficient (ffc) can vary in the range of from about 4 to about 5, or from about 5 to about 6, or from about 6 to about 7, or from about 7 to about 8, or from about 8 to about 9, or from about 9 to about 10. Similarly, in another non-limiting embodiment of the present disclosure, the aspect ratio can vary in the range of from about 0.5 to about 0.6, or from about 0.6 to about 0.7, or from about 0.7 to about 0.8, or from about 0.8 to about 0.9, or from about 0.9 to about 1.0.

[0032] The particles of the encapsulated medium chain fatty acid salts (core-shell) according to the present disclosure can be obtained through a wet granulation process selected from a fluidized bed granulation, or a high shear granulation, or a low shear granulation, or a melt granulation process, or a foam granulation. In one non-limiting embodiment of the present disclosure, the particles are obtained through a fluidized bed granulation.

[0033] In another aspect, the present disclosure provides a process for preparing the encapsulated medium chain fatty acid salt, in the form of core-shell, according to the present disclosure. In one non-limiting embodiment of the present disclosure, the process comprises the steps of: i. preparing a supersaturated aqueous solution of alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt by dissolving at least one first alkali metal salt of medium chain fatty acid or first sodium salcaprozate functionalized medium chain fatty acid salt in distilled water at a temperature in the range of from 50 °C to 60 °C and under continuous stirring; ii. introducing at least one second alkali metal salt of medium chain fatty acid or second sodium salcaprozate functionalized medium chain fatty acid salt in a fluidized bed dryer for preparing the core; and iii. spraying the supersaturated solution of process step (i) onto the resultant of process step (ii) to form a shell encapsulating the core. The first and second alkali metal salts of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salts, as present in the core and shell of the present encapsulated medium chain fatty acid salts, are the same.

[0034] In still another aspect, the present disclosure provides an oral solid dosage composition comprising: (i) an encapsulated medium chain fatty acid salt of the present disclosure; (ii) at leastone active pharmaceutical ingredient or active nutraceutical ingredient; and (iii) at least one pharmaceutically acceptable excipient or nutraceutically acceptable excipient.

[0035] In one non-limiting embodiment of the present disclosure, the oral solid dosage composition can be present in the form a tablet, a minitablet, a capsule, powder, granules, sachets, or lozenges. In another non-limiting embodiment of the present disclosure, the oral solid dosage composition is in the form of a tablet. In one non-limiting embodiment of the present disclosure, the tablet is an immediate release tablet, or a modified release tablet, or a controlled release tablet, or a sustained release tablet, or an extended-release tablet.

[0036] In yet another aspect, the present disclosure provides a tablet composition comprising: (i) an encapsulated medium chain fatty acid salt of the present disclosure; (ii) at least one active pharmaceutical ingredient; and (iii) at least one pharmaceutically acceptable excipient.

[0037] The encapsulated medium chain fatty acid salt can be present in an amount of from about 20.0 wt.% to about 70.0 wt.%, of the total tablet weight. In one non-limiting emboidment of the present disclosure, the amount of the encapsulated medium chain fatty acid salt can vary in the range of from about 20.0 wt.% to about 30.0 wt.%, or from about 30.0 wt.% to about 40.0 wt.%, or from about 40.0 wt.% to about 50.0 wt.%, or from about 50.0 wt.% to about 60.0 wt.%, or from about 60.0 wt.% to about 70.0 wt.%, of the total tablet weight.

[0038] Any active pharmaceutical ingredients (API) which are well known to persons skilled in the related art can suitably be used for the purpose of the present disclosure, for example, drugs, proteins, or peptides including macrocyclic peptides In one non-limiting embodiment of the present disclosure, the active pharmaceutical ingredient can be a drug. Any drugs having a wide range of water solubilities can suitably be used in the present pharmaceutical composition. In one non-limiting embodiment of the present disclosure, the drugs can be poorly soluble drugs of BCS class II, BCS class III, or BCS class IV.

[0039] Suitable and non-limiting examples of BCS class II drugs include glibenclamide, bicalutamide, ezetimibe, fenofibrate, glipizide, atovaquone, carbamazepine, danazol, griseofulvin, ketoconazole, toglitazone, ibuprofen, nifedipine, nitrofurantoin, phenytoin, sulfamethoxazole, trimethoprim, valproic acid, praziquantel, retinol palmitate, and sulfasalazine. Similarly, suitable and non-limiting examples of BCS class III drugs include cimetidine, acyclovir, atenolol, ranitidine, abacavir, captopril, chloramphenicol, codeine, colchicine, dapsone, ergotamine,kanamycin, tobramycin, tigecycline, zanamivir, hydralazine, hydrochlorothiazide, levothyroxine, methyldopa, paracetamol, propylthiouracil, pyrodostigmine, sodium cioxacillin, thiamine, benzidazole, didanosine, ethambutol, ethosuximide, folic acid, nicotinamide, nifurtimox, and salbutamol sulfate. Similarly, suitable and non-limiting examples of BCS class IV drugs include hydrochlorothiazide, furosemide, cyclosporin A, itraconazole, indinavir, nelfinavir, ritonavir, saquinavir, nitrofurantoin, albendazole, acetazolamide, and azithromycin.

[0040] Further, the active pharmaceutical ingredient can be present in a pharmaceutical effective amount. The amount of the active pharmaceutical ingredient can be varied depending upon various factors including, but not limiting to, type of drug or drugs being used, nature and severity of the ailment being treated / cured, the type and content of active ingredients or other ingredients contained in the pharmaceutical composition, dosage form, patient’s age, weight, health condition and eating behavior, drug adminstrati on time, and the like. The aount of active pharmaceutical ingredient aaccording to the present disclosure can vary in the range of from about 1.0 wt.% to about 70.0 wt.%, of the total tablet weight. In one non-limiting embodiment of the present disclosure, the amount of active pharmaceutical ingredient can vary in the range of from about 1.0 wt.% to about 10.0 wt.%, or from about 10.0 wt.% to about 20.0 wt.%, or from about 20.0 wt.% to about 30.0 wt.% or from about 30.0 wt.% to about 40.0 wt.%, or from about 40.0 wt.% to about 50.0 wt.%, or from about 50.0 wt.% to about 60.0 wt.%, or from about 60.0 wt.% to about 70.0 wt.%, of the total tablet weight.

[0041] The pharmaceutical acceptable excipeints which are commonly used in the oral solid dosage compositions are also suitable for use in the present composition, for example, excipients as described in Handbook of Pharmaceutical Excipient, Rows et al., Eds., 4th Edition, Pharmaceutical Press (2003) or Remington; The Science and Practice of Pharmacy (formerly called Remington’s Pharmaceutical Sciences), Alfonso R. Gennaro, ed., Lippincott Williams & Wilkins; 20th edition (Dec. 15, 2000). Examples of such excipients can include, but are not limited to, fillers, pigments, binders, disintegrating agents, lubricants, flow aids, flavors, sweeteners, preservatives, stabilizers, antioxidants, and the like.

[0042] In one non-limiting embodiment of the present disclosure, the fillers can be selected from the group consisting of monosaccharides, di saccharides, polysaccharides, inorganic acid salts, and combinations thereof. Suitable and non-limiting examples of fillers are cellulose, lactose, sucrose,sugars, starches, processed starches, mannitol, sorbitol, xylitol, lactitol, silicic acid, calcium sulfate, aluminum and magnesium silicate complexes and oxides, calcium diphosphate dihydrate and hydrosulfates, and any combinations thereof.

[0043] In one non-limiting embodiment of the present disclosure, the lubricant can be selected from the group consisting of talc, calcium stearate, magnesium stearate, polyethylene glycol, stearic acid, palmitic acid, colloidal silicon dioxide, calcium silicate, mineral oils, wax, carnauba wax hydrogenated vegetable oils, glyceryl behenate, sodium benzoate, sodium acetate, and sodium stearyl fumarate, sucrose fatty acid esters of stearic acid, palmitic acid, myristic acid, oleic acid, lauric acid, behenic acid, erucic acid, and any combinations thereof.

[0044] In one non-limiting embodiment of the present disclosure, the binder can be selected from the group consisting of polyvinyl pyrrolidone, sucrose, lactose, starch, processed starch, sugars, gum Arabic, tragacanth gum, guar gum, pectin, wax-based binders, microcrystalline cellulose, methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate hydroxypropyl methyl cellulose, hydroxyethyl cellulose, and any combinations thereof.

[0045] Further, the pharmaceutical accpetable excipeint can be present in an amount without affecting the therapeutic properties of the present oral solid doage composition or a tablet composition. The pharmaceutical acceptable excipeint can be present in an amount of from about 1.0 wt.% to about 85.0 wt.%, of the total tablet weight. In one non-limiting embodiment of the present disclosure, the amount of pharmaceutical acceptable excipient can vary in the range of from about 1.0 wt.% to about 10.0 wt.%, or from about 10.0 wt.% to about 20.0 wt.%, or from about 20.0 wt.% to about 30.0 wt.%, or from about 30.0 wt.% to about 40.0 wt.%, or from about 40.0 wt.% to about 50.0 wt.%, or from about 50.0 wt.% to about 60.0 wt.%, or from about 60.0 wt.% to about 70.0 wt.%, or from about 70.0 wt.% to about 80.0 wt.%, or from about 80.0 wt.% to about 85.0 wt.%, of the total tablet weight.

[0046] Further, the tablet compositon according to the present disclosure can be prepared by tableting methods which are well known to a person skilled in the pharmaceutical art, such as, wet granule tableting method or a dry granule tableting method or a dry direct tableting method. In one non-limiting embodiment of the present disclosure, the tablet can be prepared by dry direct tablet method or a direct compression (DC) method.

[0047] In a still another aspect, the present disclosure provides a process for preparing the tablet composition of the present disclosure, the process comprising the steps of: i. blending the active pharmaceutical ingredient, the encapsulated medium chain fatty acid salts or the encapsulated sodium salcaprozate functionalized medium chain fatty acid salt of the present disclosure, and one or more pharmaceutically acceptable additive; and ii. compressing the resulting components to obtain directly compressible tablet composition.

[0048] The tablet composition according to the present disclosure demonstrates enhanced compressibility as compared to tablets without the presence of encapsulated medium chain fatty acid salts. In one non-limiting embodiment of the present disclosure, the tablet composition demonstrates three times improved compressibility as compared to the tablets without the presence of encapsulated medium chain fatty acid salts. Further, the encapsulated medium chain fatty acid salts when used in the oral solid dosage forms (OSD) or tablets increases oral absorption of poorly soluble or permeable drugs and provide OSD forms with superior hardness. The encapsulated medium chain fatty acid salts according to the present disclosure are capable of forming a coherent tablet at 70% concentration (500-700 mg of encapsulated medium chain fatty acid salt or encapsulated sodium salcaprozate functionalized medium chain fatty acid salt in a 1000 mg tablet).EXAMPLESTEST METHODS:

[0049] Unless indicated otherwise, the following test methods were utilized in the Examples that follows:Bulk Density

[0050] Bulk density test was done via standard USP method. The material is dispensed within 100 ml graduated cylinder and mass is recorded.Particle Size Distribution

[0051] A Malvern Mastersizer 3000 was utilized for particle-size analysis. This technique measures the size distribution of particles by analyzing how a laser beam scatters as it passes through a sample. Laser diffraction measures particle size distributions by measuring the angular variation in the intensity of light scattered as a laser beam passes through a dispersed particulate sample. Large particles scatter light at small angles relative to the laser beam, while small particles scatter light at large angles. Plots of the distributions of these parameters are reported, along with statistics including (but not limited to) mean, dO.l, d0.5, and d0.9 (equivalent to dlO, d50, and d90).Particle Shape Morphology

[0052] Shape parameters were measured by microscopy using the Malvern Morphologi G3S. A small amount of powder was dispersed onto a large glass slide by means of a burst of pressurized air in a sample dispersion unit. The burst of air aerosolizes the particles in the powder, which are then allowed to fall to the glass slide via gravity. Particles are then uniformly dispersed on the glass slide surface. The aspect ratio (number distribution) is calculated based on the ratio of width to height and reported within a range of 0-1. An aspect ratio of near zero indicates that the particles are very elongated, while an aspect ratio of 1 means the particles are spherical. Spherical particles typically flow much better compared to elongated or fibrous particles.Flow PropertiesFlowdex™ Powder Flowability:

[0053] The powder flowability of the samples is measured by using Flowdex™ Powder Flow Tester. The Flowdex is a device used to measure the flowability index of powdered materials. The Flowdex intrinsic flowability method is based on the ability of a powder to fall freely through anorifice in a disk. The system comes with a set of 19 disks with orifices sizes ranging from 4 mm to 34 mm. A lower flow index of the sample means that a smaller orifice size is needed for the material to flow, implying better flowability.Brookfield Flow Function:

[0054] The Brookfield flow function test (FFT) of the samples is carried out by using Brookfield Powder Flow Tester by measuring the flow function coefficient (ffc). Samples are compressed under a load and then sheared against themselves to measure the forces between particles of the powder samples. Higher ffc indicates better flow. Further, ffc value and its correlation with flowability is illustrated in Table 1.TABLE 1 : ffc Value and its Correlation with Flowability ffc < 2 Very cohesive and non-flowing2 < ffc < 4 Cohesive4 < ffc < 1 0 Easy flowing10 < ffc Free-flowingEXAMPLE 1 : Fluidized Bed Granulation of Sodium Caprate according to the Present Disclosure (Ex. l)

[0055] In this example, a supersaturated aqueous solution (33.0 wt.% sodium caprate solution in water) was prepared by charging 10.36 kg sodium caprate to 21.03 kg of water that was heated and maintained at 50-60 degrees C for 3 hours. In another step, 99.64 kg of sodium caprate solid (d50: 30-80 microns) was charged into a fluidized bed bowl. Thereafter, the supersaturated solution of sodium caprate was sprayed onto the sodium caprate solid to obtain encapsulated sodium caprate particles having sodium caprate solid as an inner core covered with the supersaturated solution of sodium caprate as an outer shell. The encapsulated sodium caprate particles thus obtained were dried for about 1 hour.EXAMPLE 2: Encapsulated Sodium Caprate Tablets (Ex.2)

[0056] The encapsulated sodium caprate of Example 1 was further directly compressed into tablets. The composition of a typical encapsulated sodium caprate tablet is shown in Table 2. In atypical process, the encapsulated sodium caprate of Example 1 was compressed on a Styl’One, a compaction simulator, simulating a Fette 2090 press operating at ~37 RPM, to tablets with an individual tablet weight of 400 mg. 11 ,28mm flat faced tooling (TSM B) was used at compression forces (25kN) reported.TABLE 2: Encapsulated Sodium Caprate Tablet Composition.Ingredients wt. / tablet wt.%(mg)Sodium Caprate 497.5 99.5Magnesium Stearate 2.5 0.5Total 500 100

[0057] These tablets were characterized for crushing strength or hardness (kp). Their crushing strength or hardness was further compared with the tablets prepared from commercial samples of sodium caprate (commercial sodium caprate 1 and commercial sodium caprate 2). Their comparative analysis is illustrated in FIG. 1. As clearly evident from FIG.l, the encapsulated sodium caprate of present Example 1 demonstrates three times improved compressibility compared to the commercial samples of sodium caprate.

[0058] The Brookfield flow function coefficient (ffc), particle size, aspect ratio and Flowdex flowabilty of the tablet compositions of Ex.2 and tablet prepared from the commercial sample of sodium caprate 2 were also measured and provided in Table 3.TABLE 3: Characteristic Features of Tablets prepared from the Encapsulated Sodium Caprate of Example 1Test Commercial EncapsulatedSodium caprate Sodium CaprateSample 2 Tablet (Ex.2)Particle size d50 (pm) 50 240 aspect ratio 0.5 0.6Flowdex flowability (mm) 22 16Brookfiled Flow Function 3 (Cohesive) 7 (easy flowing)Coefficient (ffc)EXAMPLE 3: Encapsulated Sodium Caprate Collagen Peptide Tablets (Ex.3)

[0059] Collagen peptide was used as a model drug for preparing directly compressible tablets. A typical tablet formula is shown in Table 4. In a typical process, ingredients in weight proportions, as listed in Table 4, were blended on a Turbula mixer for ~10 min. The resultant homogenous blend was then compressed on a Styl’One, a compaction simulator, simulating a Fette 2090 tablet press operating at ~40 RPM (-90,000 tablets / hour), into tablets with an individual tablet weight of 500 mg. 7 / 16 standard concave (TSM-B) tooling was used at compression forces reported.Control Directly Compressed Collagen Peptide Tablets (CO.3A and CO.3B)

[0060] The comparative or control directly compressed tablet formulation was prepared in the same manner as described in Example 3 using the ingredients in weight proportions listed in Table 4.TABLE 4: Encapsulated Sodium Caprate Collagen Peptide Tablet CompositionIngredients wt. / tablet Ex.3 CO.3A CO.3Bwt.% wt.% wt.%Collagen Peptide 50.0 5.0 5.0 5.0Encapsulated Sodium caprate 700.0 70.0 of Example 1Commercial Sodium caprate 700.0 - 70.0Sample 1Commercial Sodium caprate 700.0 - - 70.0Sample 2Microcrystalline Cellulose 245 / q.s. 24.5 24.5 24.5Magnesium Stearate 5.0 0.5 0.5 0.5Total 1000.0 100.0 100.0 100.0

[0061] FIG. 2 illustrates the hardness (kp) of the tablet samples of Ex.3 and its comparison with tablets prepared from commercial samples of sodium caprate (commercial sodium caprate 1 and commercial sodium caprate 2). From the provided figures, it is evident that the directly compressed tablet of Ex.3 comprising the encapsulated sodium caprate of Ex.1 achieves higher tablet hardness (kp) as compared to the comparative / control tablets comprising the commercial sodium caprate sample 1 and commercial sodium caprate sample 2. Similarly, FIG 3. illustrates the tabletability profile of tablet samples of Ex. 3 on Styl’One compaction simulator using a 7 / 16 Standard Concave tooling mimicking Fette 2090 tablet press at 40 rpm (90,000 tablets.hr) with a precompression of 2.5kN and various main compression forces of 15, 20, 25, 30 and 35 kN.EXAMPLE 4: Fluidized Bed Granulation of Sodium Caprylate according to the Present Disclosure (Ex.4)

[0062] In this example, a supersaturated aqueous solution (33.0 wt.% sodium Caprylate solution in water) was prepared by charging 10.36 kg sodium caprylate to 21.03 kg of water that was heated and maintained at 50-60 degrees C for 3 hours. In another step, 99.64 kg of sodium caprylate solid was charged into a Fluidized Bed bowl. Thereafter, the supersaturated solution of sodium caprylate was sprayed onto the sodium caprylate solid to obtain encapsulated sodium caprylate particles having sodium caprylate solid as an inner core covered with the supersaturated solution of sodium caprylate as an outer shell. The encapsulated sodium caprylate particles thus obtained were dried for about 1 hour.EXAMPLE 5: Encapsulated Sodium Caprylate Collagen Peptide Tablets (Ex.5)

[0063] Collagen peptide was used as a model drug for preparing directly compressible tablets. Atypical tablet formula is shown in Table 5. In atypical process, ingredients in weight proportions, as listed in Table 5, were blended on a Turbula mixer for ~10 min. The resultant homogenous blend was then compressed on a Styl’One, a compaction simulator, simulating a Fette 2090 tablet press operating at ~40 RPM (-90,000 tablets / hour), into tablets with an individual tablet weight of 500 mg. 7 / 16 standard concave (TSM-B) tooling was used at compression forces reported.Control Directly Compressed Collagen Peptide Tablets (CO.5A)

[0064] The comparative or control directly compressed tablet formulation was prepared in the same manner as described in Example 5, using the ingredients in the weight proportions listed in Table 4.TABLE 5: Encapsulated Sodium Caprylate Collagen Peptide Tablet CompositionsIngredients wt. / tablet Ex.5 CO.5A(mg) % %Collagen Peptide 50.0 5.0 5.0Encapsulated Sodium Caprylate 700.0 70.0 of Example 4Commercial Sodium Caprylate 700.0 - 70.0Sample 1Microcrystalline Cellulose 245.0 24.5 24.5Magnesium Stearate 5.0 0.5 0.5Total 1000.0 100.0 100

[0065] FIG. 4 illustrates the hardness (kp) of the tablet samples of Ex.5 and its comparison with tablets prepared from commercial sodium caprylate sample 1 and commercial sodium caprylate Sample 2. From the provided figures, it is evident that directly compressed tablet of Ex.5 comprising the encapsulated sodium caprylate achieves higher tablet hardness (kp) as compared to the tablets comprising the commercial sodium caprylate sample 1.

[0066] While the compositions and methods of the disclosed and / or claimed inventive concept(s) have been described in terms of particular aspects, it will be apparent to those of ordinary skill in the art that variations may be applied to the compositions and / or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the disclosed and / or claimed inventive concept(s). All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the disclosed and / or claimed inventive concept(s).

Claims

We claim:

1. An encapsulated medium chain fatty acid salt in the form of core-shell, wherein (i) the core comprises at least one alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt; and (ii) the shell comprises at least one alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt encapsulating the core.

2. The encapsulated medium chain fatty acid salt according to claim 1, wherein the medium chain fatty acid includes at least one saturated fatty acid comprising 6 to 18 carbon atoms.

3. The encapsulated medium chain fatty acid salt according to claim 1, wherein the alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid salt, present in the core and shell, are the same.

4. The encapsulated medium chain fatty acid salt according to claim 1, wherein the medium chain fatty acid is selected from the group consisting of caproic acid, heptanoic acid, caprylic acid, nonanoic acid, capric acid, undecanoic acid, lauric acid, myristic acid, palmitic acid, and stearic acid.

5. The encapsulated medium chain fatty acid salt according to claim 1, wherein the alkali metal includes at least one metal selected from the group consisting of sodium, potassium, calcium, and magnesium.

6. The encapsulated medium chain fatty acid salt according to claim 1, wherein the alkali metal salt of medium chain fatty acid is selected from the group consisting of sodium caprate, sodium caprylate, and sodium laurate7. The encapsulated medium chain fatty acid salt according to claim 1 , wherein the weight ratio between the alkali metal salt of medium chain fatty acid core and the alkali metal salt of medium chain fatty acid shell varies in the range of from about 1 :5 to about 5: 1.

8. The encapsulated medium chain fatty acid salt according to claim 1, wherein the encapsulated medium chain fatty acid salt (core-shell) is in the form of particles having a particle size (d50) in the range of 150 pm to 350 pm.

9. The encapsulated medium chain fatty acid salt according to claim 8, wherein the particles are obtained through a wet granulation process selected from a fluidized bed granulation, or a high shear granulation, or a low shear granulation, or a melt granulation process, or a foam granulation.

10. The encapsulated medium chain fatty acid salt according to claim 9, wherein the particles are obtained through a fluidized bed granulation.

11. The encapsulated medium chain fatty acid salt according to claim 8, wherein the particles are characterized with Flowdex flowability index in the range of from 10 mm to 20 mm; flow function coefficient (ffc) ranging from 4 to 10, and aspect ratio, measured using Malvern Morphologi G3S, in the range of from 0.5 to 1.0.

12. A process for preparing the encapsulated medium chain fatty acid salt in the form of core-shell according to claim 1, comprising the steps of: i. preparing supersaturated aqueous solution of alkali metal salt of medium chain fatty acid or sodium salcaprozate functionalized medium chain fatty acid by dissolving at least one first alkali metal salt of medium chain fatty acid or first sodium salcaprozate functionalized medium chain fatty acid in distilled water at a temperature in the range of from 50 °C to 60 °C and under continuous stirring;ii. introducing at least one second alkali metal salt of medium chain fatty acid or second sodium salcaprozate functionalized medium chain fatty acid in a fluidized bed dryer for preparing the core; and iii. spraying the supersaturated solution of process step (i) onto the resultant of process step (ii) to form a shell encapsulating the core.

13. The process for preparing the encapsulated medium chain fatty acid salt according to claim 12, wherein the first and the second alkali metal salt of medium chain fatty acids, or the first and the second sodium salcaprozate functionalized medium chain fatty acid salt are the same.

14. The process for preparing the encapsulated medium chain fatty acid salt according to claim 13, wherein the first and the second alkali metal salt of medium chain fatty acids are selected from the group consisting of sodium caprate, sodium caprylate, and sodium laurate15. An oral solid dosage composition comprising:(i) an encapsulated medium chain fatty acid salt of claim 1;(ii) at least one active pharmaceutical ingredient or active nutraceutical ingredient; and(iii) at least one pharmaceutically acceptable excipient or nutraceutically acceptable excipient.

16. The oral solid dosage composition according to claim 15, wherein the oral solid dosage composition is in the form of a tablet, a minitablet, a capsule, powder, granules, sachets, or lozenges.

17. The oral solid dosage composition according to claim 15, wherein the oral solid dosage composition is in the form of a tablet.

18. The oral solid dosage composition according to claim 17, wherein the tablet is an immediate release tablet, a modified release tablet, a controlled release tablet, a sustained release tablet, or an extended-release tablet.

19. A tablet composition comprising:(i) an encapsulated medium chain fatty acid salt of claim 1 ; (ii) at least one active pharmaceutical ingredient; and (iii) at least one pharmaceutically acceptable excipient.

20. The tablet composition according to claim 19, wherein the active pharmaceutically ingredient is selected from the group consisting of proteins, peptides including macrocyclic peptides, and poor soluble drugs of BCS class II and BCS class IV.

21. The tablet composition according to claim 19, wherein the pharmaceutically acceptable excipient is selected from the group consisting of fillers, binders, disintegrating agents, lubricants, flow aids, and any combinations thereof.

22. The tablet composition according to claim 19, wherein the filler is selected from the group consisting of monosaccharides, di saccharides, polysaccharides, inorganic acid salts, and combinations thereof.

23. The tablet composition according to claim 19, wherein the filler is selected from the group consisting of cellulose, lactose, sucrose, sugars, starches, processed starches, mannitol, sorbitol, xylitol, lactitol, silicic acid, calcium sulfate, aluminum and magnesium silicate complexes and oxides, calcium diphosphate dihydrate and hydrosulfates, and combinations thereof.

24. The tablet composition according to claim 19, wherein the lubricant is selected from the group consisting of talc, calcium stearate, magnesium stearate, polyethylene glycol, stearic acid, palmitic acid, colloidal silicon dioxide, calcium silicate, mineral oils, wax, carnauba wax hydrogenated vegetable oils, glyceryl behenate, sodium benzoate, sodium acetate, and sodium stearyl fumarate, sucrose fatty acid esters of stearic acid, palmitic acid, myristic acid, oleic acid, lauric acid, behenic acid, erucic acid, and any combinations thereof.

25. The tablet composition according to claim 19, wherein the binder is selected from the group consisting of polyvinyl pyrrolidone, sucrose, lactose, starch, processed starch, sugars, gum Arabic, tragacanth gum, guar gum, pectin, wax-based binders, microcrystalline cellulose, methyl cellulose, carboxymethyl cellulose, copovidone, gelatin, sodium alginate hydroxypropyl methyl cellulose, hydroxyethyl cellulose, and any combinations thereof.

26. The tablet composition according to claim 19, wherein the encapsulated medium chain fatty acid salt is present in an amount of from 20.0 wt.% to 70.0 wt.%; of the total tablet weight.

27. The tablet composition according to claim 19, wherein the active pharmaceutical ingredient is present an amount of from 1.0 wt.% to 70.0 wt.%, of the total tablet weight.

28. The tablet composition according to claim 19, wherein the pharmaceutically acceptable excipient is present in an amount of from 1.0 wt.% to 85.0 wt.%, of the total tablet weight.

29. The tablet composition according to claim 19, wherein the tablet demonstrates three times improved compressibility as compared to the tablets without the presence of encapsulated medium chain fatty acid salt.

30. A process for preparing the tablet composition according to claim 19, comprising the steps of i. blending the active pharmaceutical ingredient, the encapsulated medium chain fatty acid salt, and one or more pharmaceutically acceptable excipient; and ii. compressing the components of step (i) to obtain the tablet composition.

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