DESC:Present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in the composition is in the form of a soft gelatin capsule contain sugar sphere and other pharmaceutically acceptable excipients.

Present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in the composition is prepared by preparing Tafamidis contain pellets filled in capsule.

Present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in the composition is prepared by fluid bed granulation technique.

Present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in Tafamidis is used in the percentage from 20-90%, specifically 20-70% and more specifically 20-40% from total weight of the concentration.

Present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in acidifier is used from 40-70% from the total weight of the composition.

Present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in seal coating layer is consisting 1-5% from the total weight of the composition.

Present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in seal drug coating layer consisting 30-70% from the total weight of the composition.

Present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in the composition is an extended release capsule dosage form.

Present invention relates to provide a particle size distribution of the Tafamidis may have particle size (D90) is less than 100 µm, preferably less than 50 µm, and more preferably less than 10 µm are combination thereof.

Present invention relates to a solid controlled release oral pharmaceutical composition comprising the pharmaceutically acceptable excipients is selected from acidifier, film formers, anti-tacking agents, diluents, binders, disintegrant, surfactants, lubricants, glidants, polymer, Plasticizer, wetting agent, alkalizer, solvents and coloring agents and the like or mixture thereof and optionally a pharmaceutical acceptable excipient.

Pharmaceutical composition of present invention is a having two components tablet or capsule and final composition can be tablet in tablet, capsule in capsule, tablet in capsule, mini tablets filled in capsule.

The term “Tafamidis” used herein refers to a pharmaceutically active molecule as well as its pharmaceutically acceptable salts, esters, amides, prodrugs, metabolites, enantiomers, polymorphs, analogues, etc. that induce a desired pharmacological or physiological effect. The term also includes all polymorphic forms, whether crystalline or amorphous.

The pharmaceutical composition comprises Tafamidis or its pharmaceutical acceptable salt in an amount from about 1 mg to about 1000 mg, preferably from about 50 mg to about 100 mg. According to one embodiment, Tafamidis is present in amount of about 40 mg. According to another embodiment, Tafamidis is present in amount of about 15 mg.

The pharmaceutical composition contains Tafamidis having particle size of D90 less than 200µ (microns).

The pharmaceutical composition of the present invention is a soft gelatine capsule.

The term "stable" as used herein refers to formulations that substantially retain the label amount of the therapeutically active ingredient during storage for commercially relevant times, and the drug-related impurity contents in the formulations remain within acceptable limits.

The term "about" as used herein refers to a defined range of the value by + 10 %. For example, about 2 % means 1.8 % to 2.2 %, about 5 % means 4.5 % to 5.5 %, about 10 % means 9 % to
11 % and about 40 % means 36 % to 44 %.

The term "oral dosage forms" includes all conventional oral solid dosage forms like a tablet, capsule, Oral disintegrating films or tablets, syrups, suspension, granules, pill, caplet, pellets, powder or sachet, or any other orally ingestible dosage form comprising Nirmatrelvir and its salts as an active ingredient mixed with other pharmaceutically acceptable excipients.

The terms “prevent” and “preventing” as used herein refers the prevention of the recurrence, spread or onset. It is not intended that the present disclosure be limited to complete prevention. In some embodiments, the onset is delayed, or the severity of the disease is reduced.

The articles "a" and "an" are used in this disclosure to refer to one or more than one (i.e., to at
least one) of the grammatical object of the article. By way of example, "a diluent" means one diluent or more than one diluent.

Throughout this specification and the appended claims, it is to be understood that the words "comprise", “have”, “contain” and "include" and variations such a "comprises", "comprising",
"having", "containing" "includes", "including" are to be interpreted inclusively, unless the context requires otherwise. That is, the use of these words may imply the inclusion of an element or elements not specifically recited.

Particle size analysis can be carried out via different methods. Non-limiting examples of the methods include, but are not limited to, sieve technique, wet dispersion method with laser diffraction analysis, dry dispersion method with laser diffraction analysis, or a combination thereof. Particle size analysis is not limited to the methods described herein and can be carried out using any method known to one skilled in the art. In one embodiment, particle size analysis can be performed via a sieve technique. In another embodiment, particle size analysis can be performed using a wet dispersion method (e.g., water as the dispersing agent, and analysis by
laser diffraction using, e.g., Sympatec equipment). In yet another embodiment, particle size analysis can be performed using a dry dispersion method and analysed by laser diffraction using, e.g., Sympatec equipment.

The term “particles” refers to individual drug substance particles whether the particles exist singly or are agglomerated. Thus, a composition comprising particulate Nirmatrelvir may contain agglomerates that are well beyond the size limit of about 500 µm specified herein. However, if the mean size of the primary drug substance particles (i.e., Nirmatrelvir) comprising the agglomerate are less than about 500 µm individually, then the agglomerate itself is considered to satisfy the particle size constraints defined herein and the composition is within the scope of the invention.

The pharmaceutical compositions of present invention can be prepared using wet granulation (aqueous or non-aqueous), dry granulation/roller compaction/slugging, direct compression or any other conventional technique used in manufacturing pharmaceutical dosage forms.

Suitable diluents/fillers include, but are not limited to starch, pregelatinized starch, powdered celluloses, polysaccharides, dibasic calcium phosphate anhydrous or dihydrate/ calcium hydrogen phosphate, magnesium stearate, calcium phosphate, tricalcium phosphate anhydrous, calcium carbonate, calcium citrate, tricalcium citrate, magnesium carbonate, lactose monohydrate, lactose anhydrous, microcrystalline cellulose, mannitol, dextrose, dextrin, maltodextrin, sucrose, sorbitol, xylitol, lactitol. inositol, dextrates, lactitol, maltodextrin, trehalose, and/or combinations thereof. Further, the amount of diluent is preferably in the range of 10% w/w to 90% w/w by weight of the composition.

Suitable binders include, but are not limited to acacia, alginic acid, agar, calcium carrageenan, dextrin, gelatin, liquid glucose, gum, cellulose derivatives such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, methylcellulose, microcrystalline cellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose (HPMC), ethyl cellulose, pectin, polyethylene glycol, povidone, Polysorbate 80, starch, pregelatinized starch and/or combinations thereof. Further, the amount of binder is preferably in the range of 0.5% w/w to 50% w/w by weight of the composition.

Suitable disintegrants/ Wetting agent include, but are not limited to sodium starch glycolate, croscarmellose sodium, cross-linked polyvinylpyrrolidone, Sorbitan monooleate, Span 80, Polysorbate, calcium and sodium carboxymethylcellulose, pregelatinized starch, magnesium trisilicate, cornstarch, potato starch and/or combinations thereof. Further, the amount of disintegrant is preferably in the range of 1% w/w to 25% w/w by weight of the composition.

Suitable film former may comprise but not limited to alkyl celluloses, hydroxyalkyl celluloses, ethyl cellulose, cellulose ethers, cellulose esters, nitro celluloses, polymers of acrylic and methacrylic acids and esters thereof, polyamides, polycarbonates, polyalkylenes, polyalkylene glycols, polyalkylene oxides, polyalkylene terephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, cellulose acetate, cellulose acetate butyrate, agar acetate, amylose triacetate, poly (vinyl methyl) ether copolymers, poly (orthoesters), polyacetals, poly (glycolic acid), poly (lactic acid), derivatives thereof, co-polymers thereof and a combination thereof. Preferably, the coating polymer is selected from one or more of hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose, hydroxyethyl cellulose, polymers of acrylic and methacrylic acids and esters thereof.

Suitable alkalizer may comprise but not limited to sodium bicarbonate, Magnesium carbonate potassium citrate, calcium carbonate, sodium lactate and calcium acetate.

Suitable hydrophobic release controlling agent(s) are selected from but are not limited to polyvinyl acetate dispersion, ethyl cellulose, cellulose acetate, cellulose propionate (lower, medium or higher molecular weight), cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, poly (methyl methacrylate), poly (ethyl methacrylate), poly (butyl methacrylate), poly (isobutyl methacrylate), and poly (hexyl methacrylate), poly (isodecyl methacrylate), poly (lauryl methacrylate), poly (phenyl methacrylate), poly (methyl acrylate), poly (isopropyl acrylate), poly (isobutyl acrylate), poly (octadecyl acrylate), waxes such as beeswax, carnauba wax. paraffin wax, niicrocrystalline wax, and. ozokerite; fatty alcohols such as cetostearyl alcohol, stearyl alcohol, cetyl alcohol and myristyl alcohol, and fatty acid esters such as glyceryl monostearate; glycerol monooleate, acetylated monoglycerides, tristearin, tripalmitin, cetyl esters wax, glyceryl palmitostearate, glyceryl behenate, or hydrogenated vegetable oils.

Suitable lubricants/glidants may comprise but not limited to magnesium stearate, colloidal silicon dioxide, aluminum silicate, sodium stearyl fumarate, colloidal silicon dioxide, stearic acid, calcium stearate, zinc stearate, talc, waxes, boric acid, hydrogenated vegetable oil, sodium chlorate, magnesium lauryl sulfate, starch, sodium lauryl sulfate, sodium oleate, sodium acetate, sodium benzoate, polyethylene glycol, fatty acid, fumaric acid, glyseryl palmito sulphate and/or combinations thereof. Further, the amount of lubricant is preferably in the range of 0.01% w/w to 20% w/w by weight of the composition.

Suitable lubricants may comprise but not limited to magnesium stearate, colloidal silicon dioxide, aluminum silicate, sodium stearyl fumarate, colloidal silicon dioxide, stearic acid, calcium stearate, zinc stearate, talc, waxes, boric acid, hydrogenated vegetable oil, sodium chlorate, magnesium lauryl sulfate, starch, sodium lauryl sulfate, sodium oleate, sodium acetate, sodium benzoate, polyethylene glycol, fatty acid, fumaric acid, glyseryl palmito sulphate and/or combinations thereof. Further, the amount of lubricant is preferably in the range of 0.01% w/w to 20% w/w by weight of the composition.

Suitable solvents include but are not limited to purified water, methanol, ethanol, isopropyl
alcohol, methylene chloride/ dichloromethane, chloroform, ethyl acetate, acetone and/or
mixtures thereof.

Suitable anti tacking agent include but are not limited to, dibutyl sebacate; vegetable oil, e.g., castor oil or glycerol/glycerin; or a glyceryl ester of a fatty acid, e.g., glyceryl triacetate or glyceryl monoricinoleate, polyethylene glycol, triethyl citrate, acetyl tributyl citrate, talc and/or mixtures thereof.
Pharmaceutically acceptable salts include but are not limited to Meglumine salts, HCL salt.

The pharmaceutical compositions of the present invention are meant for oral administration.

The compositions can be in the form of tablets, capsules, tablets filled in capsule, mini tablets
filled in capsule, sachets containing powder or granules, pellets, and the like.

The pharmaceutical composition of the present invention is meant for once daily or twice daily administration.

Examples of film-forming agents include polyvinyl alcohol, ethylcellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, carboxymethyl cellulose, hydroxymethylcellulose, hydroxyethylcellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate; waxes such as polyethylene glycol; methacrylic acid polymers such as Eudragit®. Alternatively, commercially available coating compositions comprising film-forming polymers marketed under various trade names, such as Opadry® may also be used.

Present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients where in the composition is used for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.

In one of the embodiments of the present invention relates to a capsule pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient wherein the composition is in the form pellets/granules/ powder filled in hard gelatin capsule.

In one of the embodiments of the present invention relates to a capsule pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient wherein the composition is in the form pellets/granules/ powder filled in hard gelatin capsule. Wherein the drug is dispersed in suitable solvent along with one or more pharmaceutically acceptable excipients, the resultant drug dispersion mixture is adsorbed on to the inert core with or without a seal coat.

In one of the embodiments of the present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in the composition is prepared by preparing Tafamidis contain pellets filled in capsule. Wherein drug is not dispersed in any solvent.

In one of the embodiments of the present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient wherein the drug is added in the intragranular. The said granules are prepared by wet or dry granulation process.

In one of the embodiments of the present invention disclosure is related to novel oral composition comprising;
a) Tafamidis or its pharmaceutically acceptable salt;
b) at least one acidifier; and
c) at least one pharmaceutically acceptable excipient selected from the group consisting of at least one surfactant; disintegrant, binder, diluent, Glidant and lubricant.

In one of the embodiments of the present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in Tafamidis is used in the percentage from 20-90%, preferably 20-70% and more preferably 20-40% from total weight of the concentration.

In one of the embodiments of the present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in soft gelatin capsule for oral administration comprises 61 mg of Tafamidis.

In one of the embodiments of the present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in soft gelatin capsule for oral administration comprises 20 mg of Tafamidis Meglumine.

In one of the embodiments of the present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in seal drug coating layer consisting 30-70% from the total weight of the composition.

In one of the embodiments of the present invention relates to process for the preparation of oral capsule pharmaceutical composition , is preparing seal coating layer with Isopropyl alcohol, water, hydroxy propyl methyl cellulose add talc slowly under stirring and continue till uniform dispersion obtained, add sugar sphere, sizing of granules with desired screen, preparing drug coating layer with sorbitan monooleate, polysorbate 80 , polyvinyl pyrrolidone K90, magnesium carbonate and Tafamidis Meglumine to form uniform dispersion, sizing of granules with desired screen, prepare film coating with ingredients and sizing of granules with desired screen and fill the pellets in suitable unit dose capsule.

In one of the embodiments of the present invention relates to an oral pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipient where in the composition is an immediate release or delayed release or extended release capsule dosage form.

In one of the embodiments of the present invention is process for preparation contain sugar sphere in the preparation of seal coating with film formers and anti-tacking agents, preparing drug coating layer with Tafamidis Meglumine and sizing of granules with desired screen, prepare film coating layer, sizing of granules with desired screen and fill the pellets in suitable unit dose sachets or capsule.

In one of the embodiments of the present invention, the process for the preparation of oral solid pharmaceutical composition with following step
a) Coating sugar spheers with a polymer coating which seal coat 1
b) Tafamedis drug coating on seal coating 1
c) Coating of film coating layer on drug coated pellets
d) film coated pellets are dried and filled in suitable capsules.

In one of the embodiments of the present invention, the process for the preparation of oral solid pharmaceutical composition with following step
a) blending of intra-granular material with surfactant and water dispersion to obtain inactive granules.
b) Inactive granules,Tafamidis Meglumine and other excepients are added and granulated by compacting by roller compaction to obtain sluggs, the obtained slugges are sized to desired size granules
c) above granules are blended with extra granular material and filled in suitable size capsule.

In one of the embodiments of the present invention to provide a particle size distribution of the Tafamidis or its salts thereof, may have particle size (D90) is less than 200 µm, preferably less than 100 µm, and more preferably less than 10 µm are combination thereof.

The process details of the invention are provided in the examples given below, which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.

Examples:
Example 1:
S.No Ingredients Qty per Capsule (mg) %w/w
61mg
Stage I
1. Sugar sphere/ MCC sphere (25/70#) 259 64.75
Seal Coating-I 0
2 Hydroxy Propyl Methyl Cellulose (HPMC 15 CPS) 5 1.25
3 Talc 3 0.75
4 Isopropyl alcohol qs
5 Purified water qs
Drug Coating –II 0
5. Tafamidis base 61 15.25
6 Polyvinyl pyrollidone K90 10 2.5
6. Sorbitan monooleate, Span 80 (E 494) 10 2.5
7. Polysorbate 80 (E 433) 30 7.5
8 Magnesuim carbonate 22 5.5
9 Purified Water qs
Drug coated Pellets weight 400 100
Film coating- III
10. Opadry clear (HPMC base) 40 440
11. Purified Water
Total weight of Pellets weight 440
Capsule Filling
16. Hard cellulose capsule shells size- 2 (Cap colour : White opaque, Body colour: White opaque) 1 Nos --
Manufacturing Process:
Seal Coating-I
1.1 Take Isopropyl alcohol and water in a suitable container then add Hydroxy Propyl Methyl Cellulose (HPMC 15 CPS) then add Talc slowly under stirring and continue till uniform dispersion obtained.
1.2 Take Sugar sphere/ MCC sphere (25/70#) in FBP and continue spraying by using the binder solution of step 1.1 and make build up 10%w/w of core materials.
1.3 During spraying keep Inlet temperature 55°C ± 10°C and Bed temperature 35°C ± 10°C, After completion of seal coating-I dry the pellets for 30 minutes with above parameters.
1.4 Check The LOD of Seal coated pellets-I of using IR moisture analyser (automode) at 105°C, If LOD is more than 1.5 % w/w continue drying un till it reaches less than 1.5% w/w
1.5. Sizing of granules with desired screen.
Drug Coating –II
1.6 Take purified water in a suitable container then add Sorbitan monooleate (Span 80), Polysorbate 80 Polyvinyl pyrollidone K90, Magnesuim carbonate and Tafamidis (base) under stirring and continue till uniform dispersion obtained.
1.7 Continue spraying by using the binder solution of step 1.6 to the pellets of step 1.5 with suitable weight buildup as per unit formula.
1.8 During spraying keep Inlet temperature 55°C ± 10°C and Bed temperature 35°C ± 10°C, After completion of seal coating-I dry the pellets for 30 minutes with above parameters.
1.9 Check The LOD of Seal coated pellets-I of using IR moisture analyser (automode) at 105°C, If LOD is more than 1.5 % w/w continue drying un till it reaches less than 1.5% w/w
1.10. Sizing of granules with desired screen.
Film coating- III
1.11 Take water in a suitable container then add Opadry clear (HPMC base) under stirring and continue till uniform dispersion obtained.
1.12 Continue spraying by using the binder solution of step 1.11 to the pellets of step 1.10 with suitable weight buildup as per unit formula.
1.13 During spraying keep Inlet temperature 55°C ± 10°C and Bed temperature 35°C ± 10°C After completion of seal coating-I dry the pellets for 30 minutes with above parameters.
1.14 Check The LOD of Seal coated pellets-I of using IR moisture analyser (automode) at 105°C, If LOD is more than 1.5 % w/w continue drying un till it reaches less than 1.5% w/w
1.15. Sizing of granules with desired screen.
1.16 Fill the pellets in suitable HG capsule shell.
Example 2:
Ingredients Qty per Capsule (mg) % w/w

Intragranular Part
Mannitol SD200/ Microcrystalline cellulose 217 87.9
Croscarmellose sodium 5 2.0
Sorbitan monooleate, Span 80 5 2.0
Polysorbate 80 20 8.1
Purified Water
Total Weight of Inactive granules 247
Roller compaction
Tafamidis Meglumine 20 5.0
Intragranular Part Granules inactive granules 247 61.8
Mannitol SD200/ Microcrystalline cellulose 105 26.3
Croscarmellose sodium 5 1.3
Polyvinyl pyrollidone K30 5 1.3
Extragranular Part 0.0
Croscarmellose sodium 10 2.5
Silicon dioxide 4 1.0
Magnesium stearate 4 1.0
Total Weight 400 100.0
Hard cellulose capsule shells size 0 (Cap colour : Light blue opaque, Body colour: White opaque 402
Manufacturing Process:
1.1 Take Purified water in a suitable container then add Sorbitan monooleate (Span -80), Polysorbate 80, under stirring and continue till uniform dispersion obtained.
1.2 Continue spraying by using the surfactant Dispersion of step 1.1 to the excipients Mannitol SD200/ Microcrystalline cellulose and Croscarmellose sodium (sifted through 425Micron screen) as per unit formula.
1.3 During spraying keep Inlet temperature 55°C ± 10°C and Bed temperature 35°C ± 10°C, After completion of spraying dry the granules for 30 minutes with above parameters.
1.4 Check The LOD of dried granuels of using IR moisture analyser (automode) at 105°C, If LOD is more than 1.5 % w/w continue drying un till it reaches less than 1.5% w/w
1.5 Sizing of granules with desired screen as inactive granules.
Roller compaction:
1.5 Intragranular Part Granules inactive granules and Tafamidis Meglumine pass through 425micron screen (40# mesh).
1.6 Mannitol SD200/ Microcrystalline cellulose, Croscarmellose sodium and Polyvinyl pyrollidone K30 pass through 425micron screen (40# mesh).
1.7 Sift the material of step 1.5 and 1.6 through 425micron screen (40# mesh).
1.8 Dry granulate the sifted materials of step 1.7 with suitable roller compaction process to get desired granules.
Extragranular Part Blending:
1.9 Roller compacted granules, Croscarmellose sodium and Silicon dioxide sifted through 425Micron screen (40#) and blend for 20minuted by using suitable blender with the sized granules of step 1.5.
1.7 Magnesium stearate sifted through 250Micron screen (60#) and lubricate with step 1.6 in suitable blender for 5 minutes.
1.8 Fill the Lubricated blend in suitable Hard cellulose capsule shells size 0 (Cap colour : Light blue opaque, Body color: White opaque.
,CLAIMS:1) A oral capsule pharmaceutical composition comprising Tafamidis or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in the composition isTafamidis pellets or granules or powder filled in capsule.

2) The oral capsule pharmaceutical composition as claimed in claim 1, wherein the Tafamidis is used in the percentage from 20-90%, preferably 20-70% and more preferably 20-40% from total weight of the concentration.

3) The oral capsule pharmaceutical composition as claimed in claim 1, wherein the seal drug coating layer comprising 20-70% from the total weight of the composition.

4) The oral capsule pharmaceutical composition as claimed in claim 1, wherein the composition contain pellets or granules or powder in the form of immediate release or extended release dosage form.

5) The process for the preparation of oral solid pharmaceutical composition as claimed in claim 1, with following step,
a) Coating sugar spheers with a polymer coating which seal coat 1,
b) Tafamedis drug coating on seal coating 1,
c) Coating of film coating layer on drug coated pellets,
d) film coated pellets are dried and filled in suitable capsules.

6) The process for the preparation of oral solid pharmaceutical composition as claimed in claim 1, with following step,
c) blending of intra-granular material with surfactant and water dispersion to obtain inactive granules,
d) Inactive granules,Tafamidis Meglumine and other excepients are added and granulated by compacting by roller compaction to obtain sluggs, the obtained slugges are sized to desired size granules,
e) above granules are blended with extra granular material and filled in suitable capsules.
7) The oral capsule pharmaceutical composition as claimed in claim 1, wherein the composition is used for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.