DESC:Unless otherwise stated, the following terms used in the specification and claims have the meanings given below:
The term "Molnupiravir" as used herein includes the base, pharmaceutically acceptable salts, polymorphs, stereoisomers and mixtures thereof, the term "pharmaceutically acceptable salt" means a salt which is acceptable for administration to a patient, such as a mammal (e.g., salts having acceptable mammalian safety for a given dosage regime). Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids.

The term, "pharmaceutically acceptable excipients" as used herein refers to diluents, disintegrants, binders, lubricants, glidants, coating agents, solvents, co-solvents, preservatives, wetting agents, thickening agents, antifoaming agents, sweetening agents, flavouring agents, antioxidants, solubulizers, plasticizers or dispersing agents and the like. The pharmaceutical compositions of the present invention may be formulated in a conventional manner using one or more pharmaceutically acceptable excipients.

The term "binder" employed in a composition of the present invention is capable for holding the ingredients together and forming the granules with required mechanical strength. The binders of instant invention include, but are not limited to, but are not limited to, polyvinylpyrrolidone (povidone), polyethlylene glycol (PEG), saccharides, gelatins, pregelatinized starches, microcrystalline cellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose (HPMC) and cellulose ethers.

The term "lubricant" employed in a composition of the present invention is capable of preventing the ingredients from clumping together and from sticking to the apparatus on which it is formed, for example, preventing adherence to the face of the upper punch (picking) or lower punch (sticking) of a compression machine. Preferred lubricants of instant invention includes, but are not limited to fatty acids or fatty acid derivatives such as calcium stearate, glyceryl monostearate, glyceryl palmitostearate, talc, magnesium stearate, sodium lauryl sulfate, sodium stearyl fumarate, zinc stearate, stearic acid or hydrogenated vegetable oil; polyalkylene glycols such as polyethylene glycol (PEG) or sodium benzoate and the like.
The term " Glidant" employed in a composition of the present invention is capable for providing bulkiness to obtain a desired pharmaceutical composition. The Glidant of instant invention includes, but are not limited to inorganic phosphates such as dibasic calcium phosphate, Colloidal Silicon dioxide (fumed silica), hydrophilic silica, calcium sulphate or dicalcium phosphate dihydrate; sugars such as lactose, lactose hydrate, lactose monohydrate, lactose anhydrate, sucrose, dextrose, erythritol, lactilol, xylitol, sorbitol, mannitol or malitol; cellulose or cellulose derivatives such as microcrystalline cellulose; Avicel, Avicel PH 101, Avicel PH 102 or Avicel PH 103, maize starch, Starcap-1500, Starlac and galenIQ-721.

The term "diluent" employed in a composition of the present invention is capable for providing bulkiness to obtain a desired pharmaceutical composition. The diluents of instant invention includes, but are not limited to inorganic phosphates such as dibasic calcium phosphate, calcium sulphate or dicalcium phosphate dihydrate; sugars such as lactose, lactose hydrate, lactose monohydrate, lactose anhydrate, sucrose, dextrose, erythritol, lactilol, xylitol, sorbitol, mannitol or malitol; cellulose or cellulose derivatives such as microcrystalline cellulose; Avicel, Avicel PH 101, Avicel PH 102 or Avicel PH 103, maize starch, Starcap-1500, Starlac and galenIQ-721.

The term "disintegrant" employed in a composition of the present invention is capable of facilitating the breakup of a pharmaceutical composition prepared from the composition when placed in contact with an aqueous medium. The disintegrants of instant invention includes, but are not limited to alginic acid or sodium alginate; cellulose or cellulose derivatives such as carboxymethylcellulose sodium, microcrystalline cellulose, croscarmellose sodium, powdered cellulose or croscarmellose; iron exchange resin such as amberlite, gums such as agar, locust bean, karaya, pectin and tragacanth, crospovidone (cross-linked homopolymer of N-vinyl-2-pyrrolidinone, i.e., cross-linked l-ethenyl-2-pyrrolidinone); Pregelatinized starch, sodium starch glycolate or starch.

The term "composition" or "pharmaceutical composition" or “dosage form” as used herein synonymously include solid dosage forms such as granules, multiunit particulate systems (MUPS), pellets, spheres, tablets, capsules, mini-tablets, beads, particles and the like; and liquid dosage forms such as solutions, suspensions, emulsions, colloids and the like, meant for oral administration.

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, syrups, suspension, granules, a pill, a tablet, a caplet, pellets, a powder or a sachet, or any other orally ingestible dosage form comprising Molnupiravir 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 terms “treat” and “treating” as used herein refers are not limited to the case where the subject (e.g., patient) is cured and the disease is eradicated. Rather, embodiments, of the present disclosure also contemplate treatment that merely reduces symptoms, and/or delays disease progression.

The term "oral dosage forms" includes all conventional oral solid dosage forms like a Tablet, capsule, Syrups, Suspension, granules, a pill, a tablet, a caplet, pellets, a powder or a sachet, or any other orally ingestible dosage form comprising Molnupiravir or its salts as an active ingredient mixed with other pharmaceutically acceptable excipients.

The term "Parenteral dosage forms” includes all conventional oral solid dosage forms like a Intramuscular injection, Intravenous injection, subcutaneous injection any other Parenteral dosage forms comprising Molnupiravir or its salts as an active ingredient mixed with other pharmaceutically acceptable excipients.

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.

The term “impurity” or “impurities,” as used herein, means those impurities specifically described herein, those derived from the process including reagents or solvents used in the process, intermediates used in the process or degradants including degradants of the compound synthesized in the process.

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.

Present invention relates to a stable pharmaceutical compositions comprising Molnupiravir or pharmaceutically acceptable salt thereof, and one or more pharmaceutical acceptable excipients; wherein Molnupiravir or pharmaceutically acceptable salt thereof is amorphous form.

Present invention relates to a stable pharmaceutical compositions comprising Molnupiravir or pharmaceutically acceptable salt thereof, and one or more pharmaceutical acceptable excipients; wherein Molnupiravir or pharmaceutically acceptable salt thereof is crystalline form.

Present invention pharmaceutical composition comprises, or is in the form of a pharmaceutically acceptable salt, as generally described below. Some preferred, but non-limiting examples of suitable pharmaceutically acceptable organic and/or inorganic acids are hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid, acetic acid and citric acid, as well as other pharmaceutically acceptable acids known per se.

In certain exemplary embodiments, the exemplary compound (Molnupiravir) contain an acidic group as well as a basic group, the compound can form internal salts, which can also be used in the compositions and methods described herein. When an exemplary compound contains a hydrogen-donating heteroatom (e.g., NH), salts are contemplated to cover isomers formed by transfer of said hydrogen atom to a basic group or atom within the molecule. Pharmaceutically acceptable salts of the exemplary compounds include the acid addition and base salts thereof. Suitable acid addition salts are formed from acids which form non-toxic salts. Examples include the acetate, adipate, aspartate, benzoate, besylate, bicarbonate/carbonate, bisulphate/sulphate, borate, camsylate, citrate, cyclamate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulphate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate, pyroglutamate, saccharate, stearate, succinate, tannate, tartrate, tosylate, trifluoroacetate and xinofoate salts. Suitable base salts are formed from bases which form non-toxic salts. Examples include the aluminium, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine and zinc salts. Hemisalts of acids and bases can also be formed, for example, hemisulphate and hemicalcium salts. Physiologically acceptable salts of the exemplary compounds are those that are formed internally in a subject administered compound for the treatment or prevention of disease. Suitable salts include those of lithium, sodium, potassium, magnesium, calcium, manganese, bile salts, amino acids thereof.

Present invention relates to a pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a compound disclosed herein, pharmaceutical composition is in the form of solid dosage form, semi-solid dosage form, liquid dosage form, gaseous dosage form, oral dosage forms, topical dosage forms and parenteral dosage forms.

Present invention described herein can be formulated in a variety of ways. Formulations containing one or more compounds can be prepared in various pharmaceutical forms, such as granules, tablets, capsules, suppositories, powders, controlled release formulations, suspensions, emulsions, creams, gels, ointments, salves, or lotions and the like. In certain embodiments, the formulations are employed in solid dosage forms suitable for simple, and preferably oral, administration of precise dosages. Solid dosage forms for oral administration include, but are not limited to, tablets, soft or hard gelatin or non-gelatin capsules, and caplets. However, liquid dosage forms, such as solutions, syrups, suspension etc. can also be utilized. In another embodiment, the formulation is administered topically. Suitable topical formulations include, but are not limited to lotions, ointments, creams, and gels. In a preferred embodiment, the topical formulation is a gel.

Present invention is solid oral pharmaceutical composition is in the form of tablet comprising Molnupiravir or pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients.

Present invention is solid oral pharmaceutical composition is in the form of capsule comprising Molnupiravir or pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients.

Present invention is solid oral pharmaceutical composition is in the form of Syrups comprising Molnupiravir or pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients.

Present invention is solid oral pharmaceutical composition is in the form of Suspension comprising Molnupiravir or pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients.

Present invention is parenteral pharmaceutical composition is in the form of Intramuscular injection comprising Molnupiravir or pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients.

Present invention is parenteral pharmaceutical composition is in the form of Intravenous injection comprising Molnupiravir or pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients.

Present invention is parenteral pharmaceutical composition is in the form of subcutaneous injection comprising Molnupiravir or pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients.

Present invention is relates to solid oral pharmaceutical composition comprising Molnupiravir or its pharmaceutical salt thereof, lubricants, Glidants, disintegrants, binders and one or more pharmaceutically acceptable excipients.

Present invention relates to a pharmaceutical tablet dosage form composition comprising Molnupiravir or its pharmaceutical salt thereof, Crospovidone, Povidone, Colloidal Silicon dioxide, Sodium Stearyl Fumarate and one or more pharmaceutically acceptable excipients.

Present invention relates to a pharmaceutical tablet dosage form composition comprising Molnupiravir or its pharmaceutical salt thereof, Microcrystalline Cellulose, Crospovidone, Povidone, colloidal silicon dioxide, sodium stearyl fumarate and one or more pharmaceutically acceptable excipients.

Present invention relates to pharmaceutical composition of the present invention can be formulated as dosage forms which include, but are not limited to, powders, granules, pills, tablets, coated tablets, capsules, pellets, patches, implants, films, liquids, semi-solids, gels, aerosols, emulsions, elixirs and the like.

Present invention relates to pharmaceutical composition of the present invention can be formulated as oral dosage forms selected from powders, granules, tablets, and capsules, powders for reconstitution, granules for reconstitution.

Present invention relates to the oral stable pharmaceutical composition comprising Molnupiravir or its pharmaceutical salt thereof, wherein the composition is in the form of tablet or capsule.

Present invention relates to oral stable tablet dosage form composition comprising 10mg, 25 mg, 50mg, 75mg, 100mg, 150mg, 200mg, 300mg, 400mg 500mg, 800mg, 1000mg of Molnupiravir base.

Present invention Molnupiravir or pharmaceutically acceptable salt thereof has a particle size distribution with a D50 of not more than 100 µm. In specific embodiments, the D50 is not more than 50 µm, not more than 20 µm, or not more than 10 µm.

Present invention Molnupiravir or pharmaceutically acceptable salt thereof has a particle size distribution with the D90 is not more than 200 µm, or not more than 100 µm.

Present invention Molnupiravir or pharmaceutically acceptable salt thereof has a particle size distribution with the D10 is not more than 20 µm, not more than 10 µm, or not more than 5 µm.

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 analyzed by laser diffraction using, e.g., Sympatec equipment.

present invention composition relates to the oral stable pharmaceutical composition comprising Molnupiravir or its pharmaceutical salt thereof having excellent stability, good purity profile, dissolution profile and bioavailability.

present invention, the pharmaceutical compositions are prepared by known technological procedures, e.g. direct compression, dry granulation or wet aqueous granulation, using well known and readily available excipients. In the preparation of the compositions of Molnupiravir, the active ingredient will usually be mixed with an excipient or mixture of excipients, or diluted by an excipient or mixture of excipients, or enclosed within an excipient or mixture of excipients which may be in the form of a capsule, sachet, paper or other container. When the excipient serves as a diluent, it may be a solid, semisolid or liquid material which acts as a vehicle or medium for the Molnupiravir.

The pharmaceutical compositions can be prepared by using any suitable method known in the art such as direct compression, dry or wet granulation (aqueous/non-aqueous or combination), extrusion spheronization, melt extrusion, melt granulation, coating over inert spheres, spray coating, spray drying and solvent evaporation.

present invention can be produced by sizing and milling a mixture of the drug substance with excipients. For example, one method for the production includes mixing the Molnupiravir with the materials for the preparation by a suitable mixer, and lubrication the mixture to tablet or capsule.

The pharmaceutical composition is meant for once daily, twice daily or thrice daily administration.

In another embodiment, the present invention relates to the oral stable composition comprising Molnupiravir or its pharmaceutical salt thereof, having dissolution more than 90% within 45 minutes.

In one of the embodiments of present invention relates to a stable pharmaceutical compositions comprising Molnupiravir or pharmaceutically acceptable salt thereof, and one or more pharmaceutical acceptable excipients.

In one of the embodiments of the present invention relates to the oral stable dosage composition comprising Molnupiravir or its pharmaceutical salt thereof and one or more pharmaceutical acceptable excipients; wherein the composition comprises at least 98 % w/w of Molnupiravir or pharmaceutically acceptable salt thereof and not more than about 1 % w/w of the one or more impurities.

In one of the embodiments of the present invention relates to a stable pharmaceutical compositions comprising Molnupiravir or pharmaceutically acceptable salt thereof, and one or more pharmaceutical acceptable excipients; wherein the composition comprises at least 99.5 % by weight Molnupiravir and not more than about 0.5 % weight of the one or more impurities.

In one of the embodiments of the present invention relates to a stable pharmaceutical compositions comprising Molnupiravir or pharmaceutically acceptable salt thereof, and one or more pharmaceutical acceptable excipients; wherein the composition comprises at least 99 % by weight Molnupiravir substantially free from impurities such as Dimethyl dioxol impurity (I), Acetyl impurity (II) and N-Hydroxycytidine impurity (III).

In one of the embodiments of the present invention relates to a stable pharmaceutical composition comprising Molnupiravir or its pharmaceutical acceptable salt thereof and one or more pharmaceutical acceptable excipients; wherein composition comprises Molnupiravir substantially free from impurities.

In one of the embodiments of the present invention substantially free we mean that the process produces impurities such as a compound of formula (I) equal to or lower than 0.15% and/or an amount of a compound of formula (II) equal to or lower than 0.15% and/or an amount of a compound of formula (III) equal to or lower than about 0.15%.

In one of the embodiments of the present invention substantially free we mean that the process produces impurities containing an amount of a compound of formula (I) typically equal to or lower than about 0.15% and typically equal to or higher than about 0.0001% and/or an amount of a compound of formula (II) typically lower than or equal to about 0.15% and typically equal to or higher than about 0.0001% and/or an amount of a compound of formula (III) typically lower than or equal to about 0.15% and typically equal to or higher than about 0.0001%.

The process of the present invention provides pure Molnupiravir, containing an amount of a compound of formula (I) typically equal to or lower than about 0.15% and typically equal to or higher than about 0.0001% and/or an amount of a compound of formula (II) typically lower than or equal to about 0.15% and typically equal to or higher than about 0.0001% and/or an amount of a compound of formula (III) typically lower than or equal to about 0.15% and typically equal to or higher than about 0.0001%.

In one of the embodiments of the present invention a mixture comprising a Molnupiravir, and a compound of formula (I) in an amount typically equal to or lower than about 0.15% and typically equal to or higher than about 0.0001%, and/or an amount of a compound of formula (II) typically lower than or equal to about 0.15% and typically equal to or higher than about 0.0001% and/or an amount of a compound of formula (III) typically lower than or equal to about 0.15% and typically equal to or higher than about 0.0001%.

In one of the embodiments of the present invention pharmaceutical composition comprising a Molnupiravir, and a compound of formula (I) in an amount typically equal to or lower than about 0.15% and typically equal to or higher than about 0.0001%, and/or an amount of a compound of formula (II) typically lower than or equal to about 0.15% and typically equal to or higher than about 0.0001% and/or an amount of a compound of formula (III) typically lower than or equal to about 0.15% and typically equal to or higher than about 0.0001%, and a pharmaceutically acceptable excipient and/or carrier.

The amount of each impurity of formula (I) or (II) or (III), in a mixture comprising a compound of Molnupiravir, and one or more said impurities of formula (I), formula (II) and formula (III), can be determined according to the usual analytic techniques. By way of example, impurities of formula (I), (II) and (III) can be detected by normal or reversed phase HPLC.

The evaluation of the content in impurities of formula (I), (II) and (III) is crucial, particularly in a process for the purification of Molnupiravir, as it affects the industrial applicability of the process itself.

In particular, a compound of formula (I) and/or a compound of formula (II) and/or a compound of formula (III) can be used as an analytical standard. Therefore, a further object of the present invention is the use of a compound of formula (I), of formula (II) and of formula (III), as an analytical standard in a process for the purification of Molnupiravir.

In one embodiment, the present invention relates to composition comprises at least 99 % w/w Molnupiravir or its pharmaceutically acceptable salt thereof, equal to or lower than 0.15% w/w of formula (V); equal to or lower than 0.15% w/w of formula (VI) and equal to or lower than 0.15% w/w of formula (VII).

In another embodiment, the present invention relates to the pharmaceutical composition comprising Molnupiravir or its pharmaceutical salt thereof for the treatment of viral infections selected from human coronavirus (covid-19), Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Chikungunya virus, Ross River virus, orthomyxoviridae virus, paramyxoviridae virus, RSV virus, influenza virus, filoviridae virus, or Ebola virus infection.

In yet another embodiment, the present invention relates to the stable pharmaceutical composition comprising Molnupiravir or its pharmaceutical salt thereof for the treatment of Covid-19 infection.

In yet another embodiment, pharmaceutical compositions disclosed herein are contemplated to be administered in combination with other the antiviral agent(s) such as PF-07321332, ritonavir, abacavir, acyclovir, acyclovir, adefovir, amantadine, amprenavir, ampligen, arbidol, atazanavir, atripla, boceprevir, cidofovir, combivir, daclatasvir, darunavir, dasabuvir, delavirdine, didanosine, docosanol, edoxudine, efavirenz, emtricitabine, enfuvirtide, entecavir, famciclovir, fomivirsen, fosamprenavir, foscarnet, fosfonet, ganciclovir, ibacitabine, imunovir, idoxuridine, imiquimod, indinavir, inosine, interferon type III, interferon type II, interferon type I, lamivudine, ledipasvir, lopinavir, loviride, maraviroc, moroxydine, methisazone, nelfinavir, nevirapine, nexavir, ombitasvir, oseltamivir, paritaprevir, peginterferon alfa-2a, penciclovir, peramivir, pleconaril, podophyllotoxin , raltegravir, ribavirin, rimantadine, ritonavir, pyramidine, saquinavir, simeprevir, sofosbuvir, stavudine, telaprevir, telbivudine, tenofovir, tenofovir disoproxil, tipranavir, trifluridine, trizivir, tromantadine, truvada, valaciclovir, valganciclovir, vicriviroc, vidarabine, viramidine zalcitabine, zanamivir, or zidovudine and combinations thereof for treatment of Covid-19 infection.

In yet another embodiment, pharmaceutical compositions disclosed herein are contemplated to be administered in combination with other the antiviral agent(s) such as PF-07321332, ritonavir or combination thereof for treatment of Covid-19 infection.

In another embodiment, the present invention relates to the oral stable dosage composition comprising Molnupiravir sodium, Crospovidone, Colloidal Silicon dioxide, Povidone, Sodium Stearyl Fumarate and one or more pharmaceutical acceptable excipients or combinations thereof.

In another embodiment, the present invention relates to the oral stable dosage composition comprising Molnupiravir sodium, Crospovidone, Colloidal Silicon dioxide, Povidone, Microcrystalline Cellulose, Sodium Stearyl Fumarate and one or more pharmaceutical acceptable excipients or combinations thereof.

In another embodiment, the present invention relates to oral stable dosage composition of
Molnupiravir, wherein said composition comprises on a total of 100 % by weight:
(a) from about 10 % to about 98 % of Molnupiravir or its pharmaceutical salt thereof,
(b) from 0 % to about 3 % of one or more disintegrant.
(c) from 0 % to about 3 % of one or more binder;
(d) from 0 % to about 3 % of Glidant;
(e) from 0 % to about 3 % lubricant; and
(f) optionally one or more pharmaceutical acceptable excipients; wherein the composition comprises less than 1% w/w of one or more impurities.

In another embodiment, the present invention relates to oral stable dosage composition of
Molnupiravir, wherein said composition comprises on a total of 100 % by weight:
(a) from about 10 % to about 98 % of Molnupiravir or its pharmaceutical salt thereof,
(b) from 0 % to about 3 % of one or more disintegrant.
(c) from 0 % to about 3 % of one or more binder;
(d) from 0 % to about 3 % of Diluent;
(e) from 0 % to about 3 % of Glidant;
(f) from 0 % to about 3 % lubricant; and
(g) optionally one or more pharmaceutical acceptable excipients;
wherein the composition comprises less than 1% w/w of one or more impurities.

In another embodiment, the present invention relates to a pharmaceutical stable dosage form composition comprising immediate release tablet.

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.

Example-1:
S.No. Ingredients Category mg/Tab % w/w
200 mg 400 mg 800 mg
1 Molnupiravir API 200.00 400.00 800.00 97.56
2 Crospovidone Disintegrant 2.00 4.00 8.00 0.98
3 Povidone K 30 Binder 2.00 4.00 8.00 0.98
4 Colloidal Silicon dioxide Glidant 0.40 0.80 1.60 0.20
5 Sodium Stearyl Fumarate Lubricant 0.60 1.20 2.40 0.30
Total 205.00 410.00 820.00 100.00

MANUFACTURING PROCESS:
1. Sifting: Sift Molnupiravir and Crospovidone, through # 30 mesh.
2. Dry Mix: Load Step 1 materials in to RMG and mix for 15 minutes at impeller 150 RPM and chopper off.
3. Binder Solution preparatin: Disperse Povidone K 30 in Purified water under stirring.
4. Granulation: Perform Granulation using contents of step 2 and step 3.
5. Wet Milling: Mill Granules of step 4 through 3 mm screen.
6. Drying: Dry contents of step 5 in Rapid Drier at 50°C temperature until LOD reaches to 1.0% to 3.0%.
7. Sizing and Milling: Seive contents of step 6 through # 24 mesh and mill retentions through 1.00 mm untill all the material passed through # 24 mesh.
8. Extragranular Sifting:
a. Sift Colloidal Silicon dioxide through # 24 mesh
b. Sift Sodium Stearyl Fumarate through # 60 mesh.
9. Lubrication:
a. Load contents of step 7 and step 8 (a) into blender and mix for 10 minutes.
b. Add contents of Step 8 (b) to contents of step 9 (a) and mix for 5 minutes.
10. Capsule filling: Fill the lubricated blend into suitable size capsules.

Example-2:
S.No. Ingredients Category mg/Capsule % w/w
200 mg 400 mg 800 mg
1 Molnupiravir API 200.00 400.00 800.00 90.91
2 Crospovidone Disintegrant 2.00 4.00 8.00 0.91
3 Povidone K 30 Binder 2.00 4.00 8.00 0.91
4 Microcrystalline Cellulose Diluent 14.40 28.80 57.60 6.55
5 Colloidal Silicon dioxide Glidant 0.50 1.00 2.00 0.23
6 Sodium Stearyl Fumarate Lubricant 1.10 2.20 4.40 0.50
Total 220.00 440.00 880.00 100.00

MANUFACTURING PROCESS:
1. Sifting: Sift Molnupiravir and Crospovidone, through # 20 mesh.
2. Dry Mix: Load Step 1 materials in to RMG and mix for 15 minutes at impeller 150 RPM and chopper off.
3. Binder Solution preparatin: Disperse Povidone K 30 in Purified water under stirring.
4. Granulation: Perform Granulation using contents of step 2 and step 3.
5. Wet Milling: Mill Granules of step 4 through 6 mm screen.
6. Drying: Dry contents of step 5 in Rapid Drier at 50°C temperature until LOD reaches to 1.0% to 1.5%.
7. Sizing and Milling: Seive contents of step 6 through # 20 mesh and mill retentions through 1.50 mm untill all the material passed through # 20 mesh.
8. Extragranular Sifting:
a. Sift Microcrystalline Cellulose & Colloidal Silicon dioxide through # 20 mesh
b. Sift Sodium Stearyl Fumarate through # 60 mesh.
9. Lubrication:
a. Load contents of step 7 and step 8 (a) into blender and mix for 10 minutes.
b. Add contents of Step 8 (b) to contents of step 9 (a) and mix for 5 minutes.
10. Capsule filling: Fill the lubricated blend into suitable size capsules.
,CLAIMS:1. A stable pharmaceutical composition comprising Molnupiravir or its pharmaceutical acceptable salt thereof and one or more pharmaceutical acceptable excipients; wherein composition comprises Molnupiravir substantially free from impurities.

2. A stable pharmaceutical composition as claimed in claim 1, wherein the pharmaceutical composition is substantially free from impurities such as Dimethyl dioxol impurity (I), Acetyl impurity (II) and N-Hydroxycytidine impurity (III).

3. A stable pharmaceutical composition as claimed in claim 1, wherein Molnupiravir or a pharmaceutically acceptable salt having particle size distribution of D10 having less than 20µm, D50 having less than 30µm and D90 having less than 100µm.

4. A process of preparation of a stable pharmaceutical composition comprising Molnupiravir as claimed in claim 1, wherein Molnupiravir is substantially free from impurities.

5. A stable pharmaceutical composition as claimed in claim 1, wherein one or more pharmaceutically acceptable excipients is Disintegrant, Binder, Glidant, Lubricant, Diluent, solvents.

6. A stable pharmaceutical composition as claimed in claim 1, wherein one or more pharmaceutically acceptable excipients is Crospovidone, Povidone K 30, Microcrystalline Cellulose, Colloidal Silicon dioxide and Sodium Stearyl Fumarate.

7. A stable pharmaceutical composition as claimed in claim 1, wherein the composition is used for the treatment of COVID-19 and influenza virus.