WO2022208156A1

WO2022208156A1 - Pharmaceutical composition of molnupiravir

Info

Publication number: WO2022208156A1
Application number: PCT/IB2021/058519
Authority: WO
Inventors: Desi Reddy SRINIVAS REDDY; Pasula BASAVAIAH CHOWDARY; Amarnath Reddy Rami Reddy
Original assignee: Optimus Pharma Private Limited
Priority date: 2021-03-29
Filing date: 2021-09-18
Publication date: 2022-10-06
Also published as: TW202237145A

Abstract

The present invention relates to a pharmaceutical composition, methods for making pharmaceutical formulations comprising Molnupiravir or pharmaceutically acceptable salt or derivatives thereof and one or more pharmaceutically acceptable excipient. The present invention further provides process for preparation of Molnupiravir.

Description

PHARMACEUTICAL COMPOSITION OF MOLNUPIRAVIR

FIELD OF THE INVENTION:

The present invention relates to a pharmaceutical composition, methods for making pharmaceutical formulations comprising Molnupiravir or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

BACKGROUND OF THE INVENTION

Molnupiravir is an experimental antiviral drug which is orally active and was developed for the treatment of influenza. It is a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, and exerts its antiviral action through introduction of copying errors during viral RNA replication. Activity has also been demonstrated against coronaviruses including SARS, MERS and SARS-CoV-2.

In April 2020 in Chemical & Engineering News (C&EN) Under drug Development section an article titled “An emerging antiviral takes aim at COVID-19” written by Bethany Halford mentioned that, Rick Bright former Head of US Biomedical Advanced Research and Development Authority (BARDA) Rick Bright in his whistle blower complaint revealed concerns over providing funding for the further development of Molnupiravir due to similar drugs having mutagenic properties (producing birth defects). A previous company, Pharmasset that had investigated the drug's active ingredient had abandoned it. These claims were denied by George Painter, CEO of DRIVE, noting that toxicity studies on Molnupiravir had been carried out and data provided to regulators in the US and UK, who permitted safety studies in humans to move forward in the spring of 2020. Also at this time, DRIVE and Ridgeback Bio therapeutics stated they planned future safety studies in animals.

As per the ClinicalTrails.gov data base there were many studies were registered for investigation of Molnupiravir which are as follows:

• On June 16, 2020 Merck Sharp & Dohme Corp, started a clinical study to Evaluate the Safety, Tolerability and Efficacy of EIDD-2801 to Eliminate Infectious Virus Detection in Persons With COVID-19

• March 2020, many of the human clinical trials were being done of the Molnupiravir for "Safety, Tolerability, and Pharmacokinetics" in healthy volunteers in the UK and US. • In June 2020, Ridgeback Bio therapeutics announced it was moving to Phase II trials to test the efficacy of the drug as a treatment for COVID-19. Two trials of small numbers of hospitalized and non-hospitalized patients in the US and the UK were underway in July.

• In late July 2020, and without yet releasing any medical data, Merck, which had been partnering with Ridgeback Bio therapeutics on developing the drug, announced its intention to move Molnupiravir to late stage trials beginning in September 2020.

• On October 19, 2020 recruiting of human volunteers for the interventional clinical trial was started for phase 2/3, randomized, placebo-controlled, double-blind clinical study, in which the efficacy, safety, and pharmacokinetics of mk-4482 in hospitalized adults with covid-19.

On December 3^rd, 2020, an article was published in the journal “Nature” on the results of a study on the treatment with Molnupiravir of ferrets infected with Covid-19. The study found that the drug was "efficacious" when administered orally to infected ferrets, and that it blocked the transmission of the virus between ferrets after 24 hours following administration of the drug.

.Molnupiravir (development codes MK-4482 and EIDD-2801) structural formula is as follows:

Molnupiravir is reported in US 20200276219 by Emory University A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Molnupiravir, process for preparation of Molnupiravir and compound of Molnupiravir. But the application does not discuss any details of the pharmaceutical composition.

Nowhere is the above mentioned state of arts there is disclosure of any pharmaceutical composition nor process of preparation of the pharmaceutical composition of Molnupiravir or its suitable dosage forms were discussed, hence there is an immense need of present invention for a detailed disclosure of Molnupiravir pharmaceutical composition and its processes of preparation of same. OBJECTIVES OF THE INVENTION

The primary Objective of the present invention is a pharmaceutical composition comprising of Molnupiravir or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipient.

The second objective of the present invention is the process of preparation of pharmaceutical composition of Molnupiravir or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipient.

Another objective of the present invention is a formulation containing Molnupiravir or a pharmaceutically acceptable salt thereof in a range from about 10 mg to about 800 mg along with and one or more pharmaceutically acceptable excipient.

Yet another objective of the present invention is preparation of Molnupiravir or oral dosage form about 10 mg to about 800 mg along with and one or more pharmaceutically acceptable excipient.

Another objective of the present invention is a formulation containing Molnupiravir or a pharmaceutically acceptable salt thereof in a range from about 10 mg to about 800 mg along with and one or more pharmaceutically acceptable excipient where is dosage form exhibits dissolution profile having drug release more than 70% within 30 minutes in 0.1N HC1900ml with 50 rpm.

Yet another objective of the present invention is preparation of Molnupiravir or oral dosage form about 10 mg to about 800 mg along with and one or more pharmaceutically acceptable excipient. This exhibits pharmacokinetic parameters after Single ascending doses where mean Cmax were up to 13.2 ng/mL Tmax is about 0.25 and 0.75 hours and after Multiple ascending doses plasma concentration-time curve dining a dosing interval (AUCτ) and Cmax between 0.938 and 1.16, and between 0.843 and 1.10, respectively, Median tmax occurred up to 0.75 hours.

Another objective of the present invention is a formulation comprising Molnupiravir or a pharmaceutically acceptable salt thereof in a range from about 10 mg to about 800 mg along with and one or more pharmaceutically acceptable excipient used for the treatment of viral infection is, or is caused by, an alphavirus, flavivirus or coronaviruses or thomyxoviridae or paramyxoviridae, or RSV, influenza, Powassan virus or filoviridae or Ebola. SUMMARY OF THE INVENTION

The present invention relates to a pharmaceutical composition, methods for making pharmaceutical composition comprising of Molnupiravir or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipient.

As used herein, the term “Molnupiravir" 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.

Accordingly, the preferred pharmaceutical composition of the present invention contains various quantities ranging from about 10 mg to about 800 mg of Molnupiravir or a pharmaceutically acceptable salt thereof. Thus, for example, the preferred formulation can contain about lOmg to 800 mg of Molnupiravir.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a pharmaceutical composition and methods for making pharmaceutical formulations comprising Molnupiravir or pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipient. The present invention further provides process for preparation of Molnupiravir.

In embodiments, a pharmaceutical composition comprises a pharmaceutically acceptable excipient, such as a pharmaceutically acceptable carrier, and an exemplary compound described herein.

In certain exemplary embodiments, the 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, sulfuric acid, nitric acid, acetic acid and citric acid, as well as other pharmaceutically acceptable acids known per se (for which reference is made to the references referred to below).

When the exemplary compounds contain an acidic group as well as a basic group, the compounds 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. For a review on suitable salts, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use by Stahl and Wermuth, incorporated herein by reference. 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.

The 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 , Parenteral dosage forms, Ophthalmic dosage form,

In certain embodiments compounds 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, lotions, or aerosols 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, shakes, 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. In another embodiment, the formulation is administered intranasal. It must be noted that, as used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

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 term "Topical dosage forms " includes all conventional oral solid dosage forms like a Ointment, Cream, gels any other Topical dosage form comprising Molnupiravir and 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 and its salts as an active ingredient mixed with other pharmaceutically acceptable excipients.

In another embodiment, the 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.

In another embodiment, the 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.

In another embodiment, the solid oral pharmaceutical composition is in the form of Syrups Suspensions or emulsions comprising Molnupiravir or pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients.

In another embodiment, the parenteral pharmaceutical composition is in the form of Intramuscular injection (or) Intravenous injection (or) subcutaneous injection comprising Molnupiravir pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients. In another embodiment, the ophthalmic pharmaceutical composition is in the form of eye drops/ophthalmic ointments and gels comprising Molnupiravir or pharmaceutically acceptable salts or derivatives thereof, and one or more pharmaceutically acceptable excipients.

The term "pharmaceutical acceptable excipients" used herein, refers to organic or inorganic ingredients, natural or synthetic, with which an active ingredient is combined to facilitate administration of a composition. Examples of suitable excipients may include, but not limited to the given examples below

According to the embodiments, the diluents are used in formulations as a diluting agent or filler or thinner. Diluents are added to ease the restricted movement. In the current invention microcrystalline cellulose, powdered cellulose, lactose (anhydrous or monohydrate), compressible sugar, fructose, dextranes, other sugars such as mannitol, sorbitol, lactitol, saccharose or a mixture thereof, siliconised microcrystalline cellulose, calcium hydrogen phosphate, calcium carbonate, calcium lactate or mixtures thereof. A preferred further diluent that also causes reduced sticking properties of tablets to the equipment used for tabletting is silica, preferably colloidal or fumed silica. Preferably, the excipients include at least one diluent selected from microcrystalline cellulose and lactosemo no hydrate can be used.

According to the embodiments, the binders are used in composition are selected from acacia, starch paste, pregelatinized starch, alginic acid, cellulose, Hydroxy propyl methyl cellulose, poly vinyl pyrolidone, poly ethylene glycol, povidone, acacia, carboxymethyl cellulose sodium, methyl cellulose, ethyl cellulose, liquid glucose, sodium alginate, candelilla wax, carnauba wax, com starch, copovidone, poly ethylene oxide, sodium starch. Permeability enhancers are also added to enhance the permeability through cells. They are not limited to following examples SLS, Tween 80, Fatty acid esters (sodium taurocholate, sodium deoxycholate) and the like

According to the embodiment, the disintegrant used in the compositions is selected from Alginic acid, citric acid, croscarmellose sodium, Crospovidone, colloidal silicone dioxide, cellulose, carboxy methyl cellulose calcium, micro crystalline cellulose, methyl cellulose, povidone, sodium starch glycolate, Hydroxypropyl methyl cellulose, sodium carmellose, starch, sodium alginate and the like

According to the embodiment, the lubricants used in the compositions is selected from stearic acid, magnesium stearate, calcium stearate, sodium lauryl sulphate. Preferred that the excipients include at least one lubricant, selected from stearic acid, magnesium stearate, calcium stearate and sodium stearyl fumarate, more preferably from stearic acid, magnesium stearate and calcium stearate and the like

According to the embodiment, the glidants used in the compositions is selected from fumed silica, magnesium carbonate, talc, colloidal silicone dioxide, tri calcium phosphate. The pharmaceutical dosage form of the invention can optionally have one or more coatings such as moisture -barrier film coating, sugar coating and other coatings known in the art.

One or more of these additives may be selected and used by the skilled artisan having regard to the particular desired properties of the pharmaceutical composition by routine experimentation and without any undue burden. The absolute amounts of each additive and the amounts relative to other additives is similarly dependent on the desired properties of the pharmaceutical composition and may also be chosen by the skilled artisan by routine experimentation without undue burden.

According to one of the embodiments of the present invention, the formulation is a conventional oral solid dosage form, preferably a capsule, granules, a pill, a tablet, a caplet, pellets, a powder or a sachet; and more preferably a capsule, comprising Molnupiravir as an active ingredient mixed with pharmaceutical carriers like diluents, disintegrant, permeability enhancer and amine derivative along with binder, glidant, lubricant which are commonly used.

In further embodiments of the 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 composition of the 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 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.

The pharmaceutical composition is meant for once daily or twice daily administration. According to one embodiment, the pharmaceutical composition comprises a solid dispersion of Molnupiravir in one or more carrier and optionally including other pharmaceutically acceptable excipients. The solid dispersion may optionally be encapsulated in hard gelatin capsules, compressed into a tablet, or may be granulated with a pharmaceutically acceptable excipients. The carrier can be hydrophilic or hydrophobic or water swellable, which include but not limited to polyethylene glycol (PEG), phospholipids, polyvinyl pyrrolidone, cellulose derivatives such as methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethylcellulose, poly (ethylene oxide), carboxyvinyl polymer, Carboxymethylethyl cellulose, polyvinylalcohol and polyvinylacetate (PVA)/PVP copolymer, guar gum, xanthan gum, sodium alginate, dextrin, cyclodextrin, crospovidone, polyacrylates polymethacrylates, urea, soluplus, sugar, polyols and their polymers, surfactants such as poloxamer, tween, gelucire and/or combinations thereof.

In certain embodiments, the present invention relates to methods of increasing bioavailability for treating or preventing a viral infection comprising administering an effective amount of a compound or pharmaceutical composition disclosed herein to a subject in need thereof.

In certain embodiments, the disclosure relates to methods of treating or preventing a viral infection comprising administering an effective amount of a compound or pharmaceutical composition disclosed herein to a subject in need thereof. In certain embodiments, the viral infection is a Zika virus infection. In other embodiments, the viral infection is Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, or RSV.

In certain embodiments, the disclosure relates to methods of treating or preventing a viral infection comprising administering an effective amount of a compound or pharmaceutical composition disclosed herein to a subject in need thereof. In certain exemplary embodiments, a method of treating or preventing a Zika virus infection is provided, the method comprising administering an effective amount of a compound or pharmaceutical composition disclosed herein to a subject in need thereof. In certain embodiments, the viral infection is, or is caused by, an alphavirus, flavivirus or coronaviruses orthomyxoviridae or paramyxoviridae, or RSV, influenza, Powassan virus or filoviridae or Ebola.

In certain embodiments, the viral infection is, or is caused by, a virus selected from MERS coronavirus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Ross River virus, Barmah Forest virus, Powassan virus, Zika virus, and Chikungunya virus. In certain exemplary embodiments, the viral infection is, or is caused by, a Zika virus.

As used herein, the terms “prevent” and “preventing” include 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.

As used herein, the terms “treat” and “treating” 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.

IN-VITRO DISSOLUTION STUDIES:

Dissolution study of test product Molnupiravir Capsules 200 mg, 400mg 800 mg was performed in order to understand % dissolution in release dissolution media. The dissolution media used for the test is 900ml of 0.1NHC1 at 50 RPM with paddle.

Dissolution Profiles:

Table: 1 Dissolution of Molnupiravir Capsules

Figure 1 Dissolution Profile of Molnupiravir capsules

Pharmacokinetic Parameters as disclosed by the innovator Bio studies:

Single and multiple doses of Molnupiravir were evaluated in this first-in-human, phase 1, 20 randomized, double-blind, placebo-controlled study in healthy volunteers, which included 21 evaluation of the effect of food on pharmacokinetics. Eligible subjects were randomized in a 3:1 ratio to either study drug or placebo in the single- and multiple-ascending-dose parts of the study. Each cohort comprised 8 subjects, with single oral doses of 50 to 1600 mg administered in the single-ascending- dose part and twice-daily (BID) 107 doses of 50 to 800 mg administered for 5.5 days in the multiple- ascending-dose part. Subjects were followed for 14 days following completion of dosing for assessments of safety, tolerability, and pharmacokinetics. Subjects in the food-effect evaluation were randomized in a 1:1 ratio to either 200 mg Molnupiravir in the fed state followed by 200 mg Molnupiravir in the fasted state, or vice versa, with a 14-day washout period between doses. A capsule formulation was used in all parts of the study, with the exception of single ascending doses ≤800 mg, where an oral solution formulation was used.

Table: 2 Molnupiravir Single Dose (50-1600mg)

On Day 1, when assessed using the power model, mean C_max and AUCinf increased in an approximately dose-proportional manner. However, the upper bound of the 90% confidence interval for C_max was slightly below unity and the lower bound of the 90% confidence interval for AUCinf was slightly above unity (Table 7). On Day 6, mean Cmax increased in a dose proportional manner, with the 90% confidence interval containing unity. Similarly, mean AUCτ increased in an approximately dose- proportional manner; however, the lower bound of the 90% confidence interval was slightly above unity.

Table: 3 Molnupiravir Twice-Daily Multiple Does (50-1600mg)

Effect tit Food on Molnupiravir Absorption:

Concentrations of Molnupiravir were generally not quantifiable and pharmacokinetic parameters were not calculable. Concentrations of EIDD-1931 were quantifiable at 0.25 hours post dose for 2 subjects in the fasted state, but no subjects in the fed state. The first quantifiable concentrations in the fed state were between 0.5 and 1.5 hours post dose.

Table 4. Pharmacokinetic parameters of EIDD-1931 (food effect)

Figure 2 Food effect on Molnupiravir capsules

200 mg molnupiravir capsule (fasted) 200 mg molnupiravir capsule (fed)

The above bio-studies data has been obtained from article published by Ridgeback Bio therapeutics (Antimicrob Agents Chemother, 2021 Mar l;65(5):e02428-20.). Clinical Study data:

The applicant of the instant invention as performed a multicentre, open label, randomized study to assess the efficacy and safety of Molnupiravir 800 mg (BID) + Standard of Care (SOC) and Standard of Care (SOC) only, in mild Covid patients.

In the above said study Patients with RT-PCR confirmed COVID-19 and satisfying all the inclusion and none of the exclusion criteria were identified and screened for the study. Eligible patients were randomized (1:1) either to receive Molnupiravir 800 mg (BID) + Standard of Care or Standard of Care only for 5 days. End of treatment assessment was performed on Day 5 (+1).

The interim results indicate that addition of Molnupiravir to SOC results in significantly faster clinical improvement in terms of reduction in score on WHO ordinal scale and also results in faster reduction of viral load as indicated by significant increase in CT values of RT-PCR tests as well as significantly higher proportion of patients achieving RT-PCR negativity on days 5 and 10. Additionally, the number of SAEs reported in the subjects who received Molnupiravir + SoC were significantly lesser, as compared to the subjects who received SoC alone. This shows that the Molnupiravir (800mg) capsule when given along with SoC increases the effectiveness as well as safety of the treatment in subjects with mild Covid-19.

Summary of Incidence of at least one TEAE by Severity-Full Analysis (N=403)

EXAMPLES

The following examples are included to further illustrate the present invention. It should not be regarded as a limitation on the present invention.

EXAMPLE 1; /Tablet (mg)

Brief Manufacturing process

Co-sift Molnupiravir, Hydroxypropyl cellulose.

Load sifted materials of step-i in Rapid Mixer Granulator and dry mix for 15 minutes.

Dissolve Pregelatinized starch in purified water under stirring and continue stirring till get clear solution. Granulate the dry mix material of step-ii using binder solution of step iii.

Unload the wet mass from RMG of step-iv and mill through co-mill fitted with 3.0 mm screen at medium speed.

Sift sodium stearyl fumarate through sieve.

Load the granules of step-ix and step-x materials in blender and mix for 10 minutes at slow speed.

EXAMPLE 2:

Brief Manufacturing nr

Co-sift Molnupiravir, Hydroxypropyl cellulose.

1. Load sifted materials of step-i in Rapid Mixer Granulator and dry mix for 15 minutes.

2. Dissolve Pregelatinized starch in purified water under stirring and continue stirring till get clear solution.

3. Granulate the dry mix material of step-ii using binder solution of step iii.

4. Unload the wet mass from RMG of step-iv and mill through co-mill fitted with 3.0 mm screen at medium speed.

5. Sift sodium stearyl fumarate through sieve. 6. Load the granules of step-ix and step-x materials in blender and mix for 10 minutes at slow speed.

EXAMPLE 3:

Brief Manufacturing process

1. Co-sift Molnupiravir, Hydroxy propyl cellulose.

2. Load sifted materials of step-i in Rapid Mixer Granulator and dry mix for 15 minutes.

3. Dissolve Pregelatinized starch in purified water under stirring and continue stirring till get clear solution.

4. Granulate the dry mix material of step-ii using binder solution of step iii.

5. Unload the wet mass from RMG of step-iv and mill through co-mill fitted with 3.0 mm screen at medium speed.

6. Sift sodium stearyl fumarate through sieve.

7. Load the granules of step-ix and step-x materials in blender and mix for 10 minutes at slow speed.

EXAMPLE 4:

Brief Manufacturing nr

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 preparation: 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 until 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 5:

Brief Manufacturing nr

1. Sifting: Sift Molnupiravir and Crospovidone, through # 30 mesh.

4. Granulation: Perform Granulation using contents of step 2 and step 3.

5. Wet Milling: Mill Granules of step 4 through 3 mm screen.

10. Capsule filling: Fill the lubricated blend into suitable size capsules.

EXAMPLE 6:

Brief Manufacturing process

1. Sifting: Sift Molnupiravir and Crospovidone, through # 30 mesh.

3. Binder Solution preparation: 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.

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.

10. Capsule filling: Fill the lubricated blend into suitable size capsules.

Claims

We Claim:

1. A pharmaceutical composition comprising of Molnupiravir or pharmaceutically acceptable salt thereof in the range of about 10 mg to about 800 mg along with one or more pharmaceutically acceptable excipients.

2. The pharmaceutical composition as claimed in claim 1, wherein Molnupiravir salts are equivalent to Molnupiravir in a range from about 10 mg to about 800 mg along with and one or more pharmaceutically acceptable excipient.

3. The pharmaceutical composition as claimed in claim 1 , wherein the composition is oral dosage form.

4. The pharmaceutical composition as claimed in claim 4, wherein the oral dosage form is in the form of Tablet, capsule, Syrups, Suspension, granules, a pill, a tablet, a caplet, pellets, a powder or a sachet, or any other orally ingestible dosage form.

5. The pharmaceutical composition as claimed in claim 4, where the oral dosage form is more preferably capsule dosage form.

6. The pharmaceutical composition as claimed in claim 1, wherein the pharmaceutically acceptable excipients are selected from a diluent, a disintegrant, a colorant, a binder, a glidant, a lubricant and the like or mixture thereof.

7. The pharmaceutical composition as claimed in claim 6, wherein preferably excipients are selected from microcrystalline cellulose, croscarmellose sodium, iron oxide yellow, povidone K-30, colloidal silicon dioxide, magnesium stearate and the like or mixture thereof and optionally a pharmaceutical acceptable excipient.

8. A pharmaceutical composition comprising of Molnupiravir or pharmaceutically acceptable salt thereof wherein the pharmaceutical composition comprising of one or more using pharmaceutical acceptable excipient selected from the group of binders or/and Lubricants.

9. The pharmaceutical composition comprising of Molnupiravir claimed in claim 8 wherein the binders are selected from but not limited to Acacia, povidone, starch derivatives, cellulose derivatives or combination thereof; wherein the lubricants are selected from but not limited to stearic acid, magnesium stearate, calcium stearate and sodium stearyl fumarate, more preferably from stearic acid, magnesium stearate and calcium stearate and the like.

10. The pharmaceutical composition comprising of Molnupiravir claimed in claim 8 The pharmaceutical composition as claimed in claim 1, wherein composition comprising of Molnupiravir or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipient used for the treatment of viral infection is, or is caused by, an alphavirus, flavivirus or coronaviruses orthomyxoviridae or paramyxoviridae, or RSV, influenza, Powassan virus or filoviridae or Ebola.