DESC:FIELD OF INVENTION:
The present invention relates to pharmaceutical composition comprising fixed dose combination of Progesterone and Dydrogesterone as luteal support regimen more particularly to oral solid composition comprising effective amount of Progesterone and Dydrogesterone and process of manufacturing thereof.
BACKGROUND:
Luteal phase is the period between ovulation and either establishment of pregnancy or onset of menstrual cycle 2 weeks later. Following ovulation, the luteal phase of a natural cycle is characterized by the formation of corpus luteum, which secretes steroid hormones estrogen and mainly progesterone. Embryonic implantation occurs during the implantation window where perfect synchronization of embryonic and endometrial signals is essential. Thus, luteal phase support is a crucial for the process of implantation and early embryonic development, any abnormalities during luteal phase causes infertility, miscarriage, failure of embryo implantation during IVF and unsuccessful assisted reproduction. Low level secretion of progesterone by corpus luteum during luteal phase is known to be major cause of luteal phase deficiency. Progesterone is essential for secretory transformation of the endometrium that permits implantation as well as maintenance of early pregnancy and is essential for successful pregnancy [Daya S. Luteal support: Progestogens for pregnancy protection. Maturitas, 2009].
The luteal support regimen involved use of micronized progesterone vaginally or dydrogesterone orally or combinations of both. However, administrating drugs through two different routes is a complex and patient non-compliance approach. Additionally, vaginal delivery of progesterone has certain limitation like inter-variation in serum progesterone levels, insufficient absorption of the drug which may limit the bioavailability of the drug and vaginal route is not well acceptable among women in certain regions. Thus, there is a need in art to develop a novel drug delivery system which avoid above mentioned drawbacks.
The present invention provides a novel drug delivery comprising fixed dose combinations (FDCs) of Progesterone and Dydrogesterone in a single dosage form which avoid the limitation of concurrent regimen and provide safe, tolerable delivery system for luteal phase support in women undergoing in vitro fertilization (IVF). FDCs formulations have unique advantages such as complementary mechanism of action, synergistic effects, better tolerability, elongated product life-cycle management, and cost savings. Use of FDCs is a rational approach for achieving optimal therapeutic benefits while minimizing multiple route of administration burden. Greater convenience with decreased pill-burden leads to improved adherence, resulting in superior clinical outcomes and greater cost-effectiveness. A key step in the design of a combination formulation is selection of effective and well- tolerated treatments. Moreover, it is essential that the components have complementary mechanisms of action and compatible pharmacokinetic profiles.

BRIEF SUMMARY OF THE INVENTION
The present invention provides a novel drug delivery composition of Progesterone and Dydrogesterone in a single dosage form for effective management of luteal phase deficiency. The current regimen for luteal support includes administered of progesterone vaginally and oral Dydrogesterone however dual route of administered is generally not preferred by patients and raised issues of non-compliance. The vaginal preparation of Progesterone has certain limitation such as inter-serum variation, low acceptability and low vaginal absorption. Thus, the present invention provides a novel, simple, safe and improved dosage form which is superior than current regimen.
In another aspect, the present invention provides an oral drug delivery system comprising pharmaceutically effective amount of Dydrogesterone and Progesterone in a single dosage form and provide a method for preparation of oral drug delivery more preferably tablet.
The present invention provides a pharmaceutical composition comprising fixed dose combinations of Dydrogesterone and Progesterone for luteal support in women undergoing in-vivo fertilization procedure with Frozen Embryo Transfers or other fertility treatment.
In one embodiment the present invention provides an immediate release formulation of Dydrogesterone and Progesterone which provides immediate onset of action and provide immediate relief.
In another embodiment the present invention sustained release formulation of Dydrogesterone and Progesterone which provide pre-determined release of the active agents with minimal side effects, reduces dose frequency and health care cost and avoid fluctuation in steady-state drug levels.

DETAILED DESCRIPTION OF THE INVENTION
Those skilled in the art will be aware that the present disclosure is subject to variations and modifications other than those specifically described. It is to be understood that the present disclosure includes all such variations and modifications. The disclosure also includes all such compositions, components of the composition, referred to or indicated in this specification, individually or collectively and all combinations of any or more of such components or composition.
Definitions
For convenience, before further description of the present disclosure, certain terms employed in the specification, and examples are collected here. These definitions should be read in the light of the remainder of the disclosure and understood as by a person of skill in the art. The terms used herein have their meanings recognized and known to those of skill in the art, however, for convenience and completeness, particular terms and their meanings are set forth below.

The articles “a”, “an” and “the” are used to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article.

The terms “comprise” and “comprising” are used in the inclusive, open sense, meaning that additional elements may be included. It is not intended to be construed as “consists of only”.

Throughout this specification, unless the context requires otherwise the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated element or step or group of element or steps but not the exclusion of any other element or step or group of element or steps.

The term “including” is used to mean “including but not limited to”. “Including” and “including but not limited to” are used interchangeably.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosure, the preferred methods, and materials are now described. All publications mentioned herein are incorporated herein by reference.

The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purposes of exemplification only. Functionally equivalent products and processes are clearly within the scope of the disclosure, as described herein.
The term “pharmaceutical composition” refers to delivery system in which active agents are delivered to the patients. This could be in the form of tablet, capsule, injection, liquid etc.

The term “pharmaceutically acceptable excipient” refers to inert substances other than active ingredients which are used in the preparation of pharmaceutical products.
The term "fixed dose combination" drug refers to a formulation of two or more medications or active ingredients combined in a single unit dosage form, and available in certain fixed doses.
The term “In vitro fertilization” or IVF is fertility treatment process which involves fertilization of eggs and sperms in vitro, the fertilized eggs are then transferred to a uterus.
The present invention relates to pharmaceutical composition comprising fixed dose combination of Dydrogesterone and Progesterone in a single dosage form.
In an embodiment the pharmaceutical composition is a novel drug delivery system comprising Dydrogesterone and Progesterone as oral dosage form most preferably solid unit dosage form.
In another embodiment the solid oral pharmaceutical composition comprising:
a. therapeutically effective amount of Dydrogesterone or salts thereof;
b. therapeutically effective amount of Progesterone or salts thereof;
c. one or more pharmaceutically acceptable excipients
The term “salt” refers to salts prepared by conventional means that include basic salts of inorganic and organic acids, including but not limited to acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate also termed esilate, fumarate, glucoheptanoate, gluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, 3- phenyl-propionate, picrate, pivalate, propionate, saccharate, succinate, tartrate, thiocyanate, tosylate and undecanoate
In one embodiment the Dydrogesterone and progesterone is present in base form.
In a preferred embodiment the composition according to invention the amount of Dydrogesterone is comprised between 5 to 50 mg.
In a preferred embodiment the composition according to invention the amount of Progesterone is comprised between 100 to 1000 mg.
In one embodiment the present invention provides a pharmaceutical composition comprising 1 to 10% of Dydrogesterone and 20% to 60% of Progesterone.
In another embodiment the novel drug delivery system is a solid unit dosage form which may be developed in form of tablets, capsules, powders, pellets, granules, microspheres, minitablets or any suitable solid unit forms known to person skilled in the art; mouth dissolving tablets; dispersible tablets; effervescent tablets; trilayer tablets; inlay tablets. In a preferred embodiment the preferred dosage form is tablet or capsule.
In another embodiment the present invention provides a tablet composition comprising Dydrogesterone and progesterone and one or more pharmaceutically acceptable excipients. Non-limiting examples of excipients that can be included in the oral dosage forms and compositions include fillers or diluents, binders, lubricants, glidants, antiadherents, flavoring agents, disintegrants, surfactants, and coloring agents.
In an embodiment the solid composition is an immediate release composition tablet comprising:
i. 5mg to 25 mg of Dydrogesterone and;
ii. 100mg to 1000 mg of Progesterone and;
iii. One or more pharmaceutically acceptable excipients
In a preferred embodiment the immediate release composition tablet according to invention the pharmaceutically acceptable excipients are selected from the group consisting of diluent, disintegrant, binder, surfactant, lubricant and glidants.
In another embodiment the present invention provides an immediate release tablet comprising of 1% to 10% of Dydrogesterone and 20% to 60% of Progesterone.
In one embodiment immediate release tablet comprises diluent selected from such as lactose monohydrate, lactose anhydrous, mannitol, starch, maize starch, corn starch, pregelatinized starches, cellulose derivatives such as crystalline cellulose and powdered cellulose, microcrystalline cellulose, and microcrystalline cellulose, sorbitol and xylitol, calcium carbonate, magnesium carbonate, dibasic calcium phosphate, and tribasic calcium phosphate.
In an embodiment the diluent present in immediate release tablet is in amount ranging of 10% to 40%.
Disintegrants that are used in embodiments of the present invention include but are not limited to crosslinked polyvinylpyrrolidone (crospovidone), croscarmellose sodium, carmellose calcium, carboxymethyl starch sodium, sodium starch glycolate, starch, pregelatinized starch, low-substituted hydroxypropylcellulose, magnesium alumino-metasilicate and ion exchange resins like polacrilin potassium; or combination thereof.
In a preferred embodiment the disintegrant present in immediate release tablet is in amount ranging from 1 to 10%
Binders that are used in embodiments of the present invention include but are not limited to, hydroxypropylcellulose, hydroxypropyl methylcellulose, also called hypromellose or HPMC, methylcellulose, carboxymethylcellulose, hydroxycellulose, hydroxyethylcellulose, cross-linked PVPs (crospovidones), vinylpyrrolidone-vinylacetate copolymers (copovidones), polyvinyl alcohol, microcrystalline cellulose (MCC), powdered acacia, gelatin, guar gum, natural or synthetic gum, polymethacrylates, polyethylene glycole (PEG, macrogol), starches, pregelatinized starch, carbomer or combinations thereof.
In a preferred embodiment the binder present in immediate release tablet is in amount ranging from 1 to 10%
Surfactants that are used in embodiments of the present invention include but are not limited to poloxamers, sodium lauryl sulfate sodium stearyl sulfate sodium oleyl sulfate and sodium cetyl sulfate,sodium dodecyl benzene sulfonate and, Docusate, polyethylene glycol and polysorbates preferably Tween 20, Tween 80 or Span 80; fatty acid esters, preferably propylene glycol caprylates such as Capmul PG- 8, Capryol 90; esters of glycerol and fatty acids, preferably glycerol oleates and caprylates (Capmul MCM); esters of polyethylene glycol and fatty acids, such as Labrasol and Solutol; castor oil ethoxylate (glycerol polyethylene glycol ricinoleate) such as Cremophor EL and Cremophor RH 40.
In a preferred embodiment the surfactant present in immediate release tablet is in amount ranging from 1 to 10%.
Lubricants that are used in embodiments of the present invention include but are not limited to magnesium stearate, glyceryl monostearate, palmitic acid, talc, carnauba wax, calcium stearate, sodium stearate, sodium lauryl sulfate, magnesium lauryl sulfate, zinc stearate, polyoxyethylene monostearate, calcium silicate, silicon dioxide, hydrogenated vegetable oils and fats, stearic acid, and mixtures thereof.
In a preferred embodiment the lubricant present in immediate release tablet is in amount ranging from 0.05 to 5%.
Glidants that are used in embodiments of the present invention include but are not limited to colloidal silicon dioxide, talc, and mixtures thereof.
In a preferred embodiment the glidant present in immediate release tablet is in amount ranging from 0.05 to 5%.
In one embodiment the present invention provides an immediate release tablet comprising:
i. 1 to 10% of Dydrogesterone and;
ii. 20 to 60% of Progesterone and;
iii. 10 to 40% of diluent
iv. 1 to 10% of Disintegrant and;
v. 1 to 10% of binder and;
vi. 1 to 10% of surfactant and;
vii. 0.05 to 5% of lubricant and;
viii. 0.05 to 5% of glidant
The present invention is an immediate release tablet comprising:
i. 2 % of Dydrogesterone (micronized) and;
ii. 40 % of Progesterone
iii. 10 % of crospovidone as disintegrant and;
iv. 19.8 % of starch and 125 mg of lactose as diluents and;
v. 2 % of Docusate as surfactant and 3% of Sodium lauryl sulphate and;
vi. 3 % of Povidone and as binder and;
vii. 0.6 % of colloidal silicon dioxide as glidant and;
viii. 0.6 % of magnesium stearate as lubricant
In an embodiment the solid composition is a monolayer tablet, preferably film coated tablet.
In another embodiment the present invention can be developed in form of bi-layer or multi-layer tablet or tablet-in-tablet formulation.
The pharmaceutical composition of present invention can be prepared by using various granulation techniques known to the person skilled in the art, such as, but not limited to direct compression, wet granulation, dry granulation, hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion, and solvent evaporation.
The components of the pharmaceutical composition defined hereinbefore can be brought together into a suitable composition for oral administration according to standard practice and procedures well known in the art of pharmaceutical science using conventional formulation and manufacturing techniques.
The tablet composition of the present invention can be coated with a coating. Various coating types known in the art can be utilized in the present invention. Examples of coating types include without limitation, film coatings, enteric or pH dependent coatings, delayed release coatings, and the likes thereof.
Suitable film-forming agents and coating materials, if used, may include, but are not limited to hydroxypropyl methylcellulose (Hypromellose), hydroxypropyl cellulose, polyvinylalcohol, methylcellulose, AKOAT, ethylcellulose, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, shellac, liquid glucose, hydroxyethyl cellulose, polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinylacetate such as Kollidon® VA64 BASF, copolymers of acrylic and/or methacrylic acid esters with trimethylammoniummethylacrylate, copolymers of dimethylaminomethacrylic acid and neutral methacrylic acid esters, polymers of methacrylic acid or methacrylic acid esters, copolymers of acrylic acid ethylester and methacrylic acid methyl ester, and copolymers of acrylic acid and acrylic acid methylester and the like.
In another embodiment the present invention provides a sustained release formulation of Progesterone and Dydrogesterone which results in reduction of dose frequency and maintained a predetermined rate by maintaining a constant drug level for a specific period of time with minimum side effects.
In one embodiment the present invention provides a sustained release tablet comprising 1% to 10% of Dydrogesterone and 30% to 60% of Progeseterone.
In an alternative embodiment the present invention provides an oral sustained release formulation further comprises release controlling agent and one or more pharmaceutically acceptable excipients.
In another embodiment there is provided a process of preparing the solid oral pharmaceutical composition of Progesterone and Dydrogesterone wherein Progesterone is optionally micronized.
Non-limiting examples of acceptable fillers, sometimes referred to as diluents, include mannitol, lactitol, dextrose, sucrose, maltose, starch, microcrystalline cellulose, lactose, isomalt, and combinations thereof.
Examples of binders that can be used in sustained release tablet include, but are not limited to copovidone, hydroxypropylcellulose, povidone, ethyl cellulose, hydroxypropyl methylcellulose, carboxymethylcellulose sodium, polyvinylpyrrolidone, sugars, starches, and combinations thereof.
In an embodiment the sustained release tablet comprises binder present in an amount ranging from 1 to 10%
In one embodiment the sustained release tablet comprises diluent present in an amount ranging from 1 to 20%.
Glidants or lubricants that can be used in the sustained release tablet, but are not limited to colloidal silicon dioxides, talc, magnesium stearate, dibasic calcium phosphate, sodium stearyl fumarate, calcium stearate, stearic acid, polyethylene glycols, silicon dioxide, and combinations thereof.
In one embodiment the sustained release tablet comprises glidant in an amount ranging from 0.05 to 5%.
In one embodiment the sustained release tablet comprises lubricant in an amount ranging from 0.05 to 5%.
Examples of surfactants that can be included in the sustained release tablet include without limitation, sodium lauryl sulfate, polysorbates, sodium taurochloate, and combinations thereof.
Examples of polymer that can be included in the sustained release tablet include methyl cellulose, Carbopol, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose; polyacrylates, methyl acrylates, polyethylene oxides, polyethylene glycols, chitosan, gums, starch derivatives, polyurethanes, galactomannans, polysaccharides, polyalcohols, acrylic acid or acrylamide derivatives, ethyl cellulose, glycerol palmitostearate, beeswax, glycowax, carnaubawax, hydrogenated vegetable oil, glycerol monostearate, stearylalcohol, glyceryl behenate, polyanhydrides, methyl acrylates, pectin, zein, modified zein, casein, gelatin, gluten, serum albumin, or collagen, chitosan, oligosaccharides and polysaccharides such as cellulose, dextrans, tamarind seed polysaccharide, gellan, carrageenan, xanthan gum, gum Arabic; hyaluronic acid, polyhyaluronic acid, alginic acid, sodium alginate, cross- linked sodium carboxymethylcellulose, cross-linked hydroxypropylcellulose, hydroxyethylcellulose, high-molecular weight hydroxypropylmethylcellulose, carboxymethylamide, potassium methacrylatedivinylbenzene co-polymer, polymethylmethacrylate, cross-linked polyvinylpyrrolidone, hydroxyethyl cellulose high- molecular weight polyvinyl alcohols, polyethyleneoxides or combinations thereof.
In preferred embodiment the sustained release tablet comprising polymer in an amount ranging from 0.5 to 20%.
In an embodiment the present invention provides sustained release tablet comprising:
i. 1 to 10% of Dydrogesterone and;
ii. 30 to 60% of Progesterone and;
iii. 1 to 10% of binder and;
iv. 1 to 20% of diluent and;
v. 0.005% to 5% of glidant and lubricant and;
vi. 0.5 to 20% of polymer.
In another embodiment the present invention is a sustained release tablet comprising:
i. 2.6% of Dydrogesterone (micronized) and;
ii. 52% of Progesterone and;
iii. 2 to 10% of microcrystalline cellulose as diluent and;
iv. 8.5% of hydroxypropylmethylcellulose (HPMC) as polymer and;
v. 2.46% of Povidone as binder and;
vi. 1.03% of Carbopol as polymer
vii. 0.4% of Colloidal silicon dioxide and 1.03% of Talcum as glidant and;
viii. 0.8% of magnesium stearate as lubricant
In another embodiment the present invention provides an oral formulation of Dydrogesterone and Progesterone for luteal-phase support in women undergoing IVF.
The present invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Example-1 Formula for Progesterone and Dydrogesterone sustained release tablet
S. No. Ingredients Function %*
1. Progesterone*
(Natural micronized) API 30-60
2. Dydrogesterone (Micronized) API 1-10
3. Micro crystalline cellulose (PH-102) Diluent 1-20
4. HPMC K-100 M Polymer 0.5-20
5. Povidone (PVPK- 30) Binder 1-10
6. Isopropyl alcohol Vehicle 5-20
7. Micro crystalline Cellulose (PH-102) Diluent 1-20
8. HPMC K-100 M Polymer 0.5-20
9. Carbopol 974 P Polymer 0.5-20
10. Talcum Glidant 0.005-5
11. Colloidal silicon dioxide Glidant 0.005-5
12. Magnesium Stearate Lubricant 0.005-5
13. Akoat-512# Film former --
14. Purified water Solvent --

*based on total weight of uncoated tablet
Process of manufacturing Progesterone and Dydrogesterone sustained release tablet
Procedure:
1. Geometrically mixing of Progesterone & Dydrogesterone with Methocel K100 premium & microcrystalline cellulose PH 102. Then sift through 40#
2. Load the above geometrical mixed powder in RMG bowl. Mix the contents for 10 min at impeller speed of “slow or fast” and chopper “off”. Scrape down the powder blend from the sides and lid of mixer and close the lid.
3. Take isopropyl alcohol in stainless steel container, Add the Povidone K-30 under continuous stirring, Stir the solution continue until Povidone K-30 is completely dissolved & clear solution is formed.
4. Add Binder solution into the dry mix powder. Knead the mass till the desired granules is formed.
5. Load the wet mass FBD. Continue Heat dry at temperature of 55-65°C till loss on drying reaches to between 1.5 % to 2.5% w/w (Check at 70°C, at Auto mode, using Halogen Moisture Balance).
6. Sift the dried granules through # 24 sieve and collect the # 24 passed granules in a double polybag lined container
7. Add sifted granules & microcrystalline cellulose PH 102, Methocel K 100 M Premium, Carbopol 974 P, Talcum & colloidal silicone dioxide in the blender. Blend the contents for 10 minutes at 12 rpm. After then add Magnesium Stearate and blend for 3 min.
Example-2 Formula for Progesterone and Dydrogesterone immediate release tablet
S. No. Ingredients Function Mg/Tab % *
1. Dydrogesterone Active 10.000 2
2. Progesterone Active 200.000 40
3. Crospovidone Disintegrants 10.000 2
4. Lactose monohydrate Diluents 125.000 25
5. Starch Diluents 99.000 19.8
6. Docusate sodium Surfactants 10.000 2
7. Povidone K-30 Binder 15.000 3
8. Isopropyl Alcohol Solvent Q.s Q.S
9. Sodium lauryl sulpahte Surfactant 15.000 3
10. Crospovidone Disintegrants 10.000 2
11. Colloidal silicon dioxide Glidant 3.000 0.6
12. Magnesium Stearate Lubricant 3.000 0.6
Coating
1. Akoat-512 Film Former 14.5 --
2. Ferric Oxide Yellow Colour 0.500 --
3. Purified Water Solvent 150.00 --

*based on total weight of uncoated tablet
Process of manufacturing Progesterone and Dydrogesterone immediate release tablet
Procedure:
1. Geometrically mixing of Progesterone & Dydrogesterone with Crosspovidone & Lactose & Starch. Then sift through 40#
2. Load the above geometrical mixed powder in RMG bowl. Mix the contents for 10 min at slow impeller speed.
3. Take isopropyl alcohol in stainless steel container, Add the Docusate Sodium Completed Dissolve then Add the Povidone K-30 under continuous stirring, Stir the solution continue until Povidone K-30 is completely dissolved & clear solution is formed.
4. Add Binder solution into the dry mix powder. Knead the mass till the desired granules is formed.
5. Load the wet mass FBD. Continue Heat dry at temperature of 55-65°C till loss on drying reaches to between 1.5 % to 2.5% w/w (Check at 70°C, at Auto mode, using Halogen Moisture Balance).
6. Sift the dried granules through # 24 sieve and collect the # 24 passed granules in a double polybag lined container
7. Add sifted granules & Sodium Lauryl sulphate, Crosspovidone, colloidal silicone dioxide in the blender. Blend the contents for 10 minutes at 12 rpm. After then add Magnesium Stearate and blend for 3 min.

,CLAIMS:We claim:
1. A pharmaceutical composition comprising effective amount of Dydrogesterone or pharmaceutically acceptable salts thereof and Progesterone or pharmaceutically acceptable salts thereof.
2. The composition as claimed in claim 1, wherein Dydrogesterone is present in amount ranging from 1% to 10%.
3. The composition as claimed in claim 1, wherein Progesterone is present in an amount ranging from 20% to 60%
4. The composition as claimed in claim 1, wherein the said pharmaceutical composition is an immediate release tablet, sustained release tablet, bilayer tablet or capsule.
5. The composition as claimed in claim 4, wherein said pharmaceutical composition is an immediate release tablet comprising:
i. 1% to 10% of Dydrogesterone and;
ii. 20% to 60% of Progesterone and;
iii. One or more pharmaceutically acceptable excipients
6. The composition as claimed in claim 5, wherein pharmaceutically acceptable excipients are selected from the group consisting of diluents, disintegrants, binders, surfactants, glidants and lubricants.
7. The composition as claimed in claim 4, wherein said pharmaceutical composition is a sustained release tablet comprising:
i. 1 to 10% of Dydrogesterone and;
ii. 20 to 60% of Progesterone and;
iii. One or more pharmaceutically acceptable excipients
8. The composition as claimed in claim 7, wherein pharmaceutically acceptable excipients are selected from the group consisting of diluents, disintegrants, binders, surfactants, glidants, polymers and lubricants.
9. The composition as claimed in claim 5 is an immediate release tablet comprising:
i. 1 to 10% of Dydrogesterone and;
ii. 20 to 60% of Progesterone and;
iii. 10 to 40% of diluent and;
iv. 1 to 10% of disintegrant and;
v. 1 to 10% of surfactant;
vi. 1 to 10% of binder and;
vii. 0.05 to 5% of lubricant and
viii. 0.05 to 5% of glidant
10. The composition as claimed in claim 7, wherein said sustained release tablet comprising:
i. 1 to 10% of Dydrogesterone (micronized) and;
ii. 30 to 60% of Progesterone and;
iii. 1 to 20% of diluent and;
iv. 1 to 10% of binder and;
v. 1 to 20% of diluent and;
vi. 0.005 to 5% of glidant and lubricant and
vii. 0.5 to 20% of polymer

Dated this 19th December of 2023

Siddhartha Dulakakhoria
DGM-IPR
Akums Drugs & Pharmaceuticals limited