DESC:
TECHNICAL FIELD OF THE INVENTION
The present invention discloses a pharmaceutically acceptable composition of olaparib or a pharmaceutically acceptable salt or a solvate thereof. The invention also relates to a method of preparation of such compositions of olaparib or pharmaceutically acceptable salts or solvate thereof and their use in treatment of cancer, either as a sole agent or in combination with other therapies.
BACKGROUND OF THE INVENTION
Olaparib is an FDA-approved targeted therapy for cancer. It is a PARP inhibitor, inhibiting polyADPribosepolymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which, include some ovarian, breast, and prostate cancers. It is marketed in the form of tablets under the trade names Lynparza® in the United States and is chemically known as 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one and has the following chemical structure:


Synthesis of olaparib was first described in patent application WO2004080976. Olaparib exhibits polymorphism, i.e., it crystallizes in various modifications that may principally differ with their physicochemical characteristics (solubility, stability etc.). Polymorphic form A, which is used in the Lynparza preparation, was characterized in patent application WO2008047082. Patent application WO2009050469 then described crystalline form L. The document of the European Medicines Agency of October 23, 2014 (EMA/CHMP/789139/2014) mentions that olaparib is a substance with low solubility and bioavailability, which means that it is classified in Group 4 of the Biopharmaceutical Classification System. Olaparib was initially approved as 50 mg capsule. The recommended daily dose of the lipid-based drug form Lynparza® 50 mg, i.e., a crystalline suspension of olaparib Form A in the fatty excipient Gelucire™, is twice 400 mg, which represents 16 capsules a day.
WO2010041051 describes various approaches to increase solubility and bioavailability of olaparib. Based on dissolutions and pharmacokinetic data, the authors infer that for the preparation of a drug form with increased bioavailability conversion of crystalline olaparib to an amorphous solid solution with polymers exhibiting low hygroscopicity and a high glass transition temperature (Tg) or melting point (Tm), i.e., higher than 100°C, will be most advantageous.
U.S. Patent No. 8,475,842 discloses oral formulation of olaparib containing solid dispersion of olaparib in copovidone, prepared by hot-melt extrusion method, to improve its bioavailability. The method of producing the solid dispersion involves mixing of olaparib with copovidone, raising the temperature of the mixture to produce a melt and extrusion of the melt to produce a solid dispersion.
Chinese Publication No. 104434809 discloses oral formulation of olaparib containing solid dispersion of olaparib in povidone, prepared by hot-melt extrusion method and solvent evaporation method.
EP3263095, discloses the solid dispersion of olaparib using hydrophilic polymer preparation of 40-100 ? with glass transition temperature, and the ratio of olaparib to polymers is in the range of 1:0.5 to 1:5, preferably in the range of 1:1 to 1:3, specifically the Soluplus and Eudragit series of polymers with low glass transition temperature are disclosed in this invention. In many of its examples, after being placed at 40° C. and 75% RH for 10 days (Eudragit E1001:1, 1:3), an endothermic peak appeared in DSC, and the stability of the solid dispersion was poor in this invention.
The prior arts described above discloses olaparib solid dispersion preparation using a large amount of polymers as an adjuvant to improve drug bioavailability, and patient has the problem of convenience of administration during administration. Thus, there remains the need for olaparib solid dispersion formulation, where the amount of adjuvants used in the formulation can be decreased and the formulation remains stable with enhanced dissolution and which increases the convenience of medication for patients. The inventors of the present invention solved the problem by synergistically using mixture or mixture of polymers in the present invention which significantly improve the dissolution behavior of the active ingredient i.e., olaparib, and thereby decrease the amount of excipients used and improve the bioavailability of active ingredients and are easy to industrialize production.
OBJECT OF THE INVENTION
The present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof.
In one aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and pharmaceutically acceptable excipients
In still another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and optionally polymers in combination with a dissolution enhancing agent and pharmaceutically acceptable excipients.
In another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and optionally polymers in combination with a dissolution enhancing agent and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg.
In still another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg; and wherein the ratio of olaparib to mixture of polymers is in the ratio of 1:1 to 1:4
In yet another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and optionally polymers in combination with a dissolution enhancing agent and other pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the matrix polymers are selected from copovidone, hypromellose phthalate (hydroxypropylmethylcellulose phthalate, HPMCP), hypromellose acetate succinate (hydroxypropylmethylcellulose acetate succinate, HPMCAS), -2-hydroxypropyl-.beta.-cyclodextrin (HPBCD), povidone, (polyvinyl pyrrolidone, PVP homopolymer), hypromellose (hydroxypropylmethylcellulose, HPMC), polymethacrylates (poly(methacrylic acid, methyl methacrylate 1:1; poly(methacrylic acid, ethyl acrylate) 1:1), hydroxypropyl cellulose (HPC), and cellulose acetate phthalate (CAP) and mixtures thereof.
In yet another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the ratio of olaparib to copovidone is present in the ratio of 1:0.5 to 1:1.5
In yet another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the ratio of olaparib to povidone is present in the ratio of 1:0.9 to 1:3
In yet another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the ratio of olaparib to copovidone to HP ß cyclodextrin is present in the ratio of 1:0.9:1:3
In still another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the copovidone and HP ß cyclodextrin is present in the ratio of 1:0.5 to 1:2
In still another aspect the present invention relates to preparation of olaparib solid dispersion by melt extrusion. Such a method comprises adding olaparib, or a pharmaceutically acceptable salt or solvate thereof, and polymer, and any additional optional excipients, including plasticisers, to a melt extrusion apparatus which then heats and mixes and finally extrudes the solid dispersion product. The extruder heats the mixture to a temperature high enough to melt the mixture but low enough so as to not degrade the constituents.
In still another aspect the present invention relates to preparation of olaparib solid dispersion by solvent evaporation. Such a method comprises preparation of solvent solution and adding olaparib or a pharmaceutically acceptable salt or solvate thereof and heating on oil bath to get a clear solution and spray the clear solution on to the suitable fillers like microcrystalline cellulose and then dry the granules obtained followed by blending, lubrication, compression and coating.
In an aspect the present invention relates to solid dispersion of olaparib or pharmaceutically acceptable salt or solvate thereof is in amorphous state or at least 90% of the olaparib is in amorphous state or at least 85% of the olaparib is in amorphous state.
In another aspect the present invention relates to method of treating cancer such as breast and ovarian cancer in the patient comprising administration to a patient in need thereof of a therapeutically effective amount of a formulation comprising olaparib or a pharmaceutically acceptable salt or solvate thereof, in solid dispersion with one or more matrix polymers or mixture of polymers. In such aspects, the medicament may comprise from 10 to 1500 mg of olaparib, such as from 10 to 1000 mg and from 25-400 mg.
DESCRIPTION OF INVENTION
The present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof.
In one aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and pharmaceutically acceptable excipients
In still another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and optionally polymers in combination with a dissolution enhancing agent and pharmaceutically acceptable excipients.

In another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and optionally polymers in combination with a dissolution enhancing agent and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg.
In still another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg; and wherein the ratio of olaparib to mixture of polymers is in the ratio of 1:1 to 1:4
In yet another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and optionally polymers in combination with a dissolution enhancing agent and other pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the polymers are selected from copovidone, hypromellose phthalate (hydroxypropylmethylcellulose phthalate, HPMCP), hypromellose acetate succinate (hydroxypropylmethylcellulose acetate succinate, HPMCAS), -2-hydroxypropyl-.beta.-cyclodextrin (HPBCD), povidone, (polyvinyl pyrrolidone, PVP homopolymer), hypromellose (hydroxypropylmethylcellulose, HPMC), polymethacrylates (poly(methacrylic acid, methyl methacrylate 1:1; poly(methacrylic acid, ethyl acrylate) 1:1), hydroxypropyl cellulose (HPC), and cellulose acetate phthalate (CAP) and mixtures thereof.
In yet another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the ratio of olaparib to copovidone is present in the ratio of 1:0.5 to 1:1.5
In yet another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the ratio of olaparib to povidone is present in the ratio of 1:0.9 to 1:3
In yet another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the ratio of olaparib to copovidone to HP ß cyclodextrin is present in the ratio of 1:0.9:1:3
In still another aspect, the present invention relates to solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising polymers or mixture of polymers and pharmaceutically acceptable excipients wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the copovidone and HP ß cyclodextrin is present in the ratio of 1:0.5 to 1:2
In still another aspect the present invention relates to preparation of olaparib solid dispersion by melt extrusion. Such a method comprises adding olaparib, or a pharmaceutically acceptable salt or solvate thereof, and polymer, and any additional optional excipients, including plasticisers, to a melt extrusion apparatus which then heats and mixes and finally extrudes the solid dispersion product. The extruder heats the mixture to a temperature high enough to melt the mixture but low enough so as to not degrade the constituents.
In still another aspect the present invention relates to preparation of olaparib solid dispersion by solvent evaporation. Such a method comprises preparation of solvent solution and adding olaparib or a pharmaceutically acceptable salt or solvate thereof and heating on oil bath to get a clear solution and spray the clear solution on to the suitable fillers like microcrystalline cellulose and then dry the granules obtained followed by blending, lubrication, compression and coating.
In an aspect the present invention relates to solid dispersion of olaparib or pharmaceutically acceptable salt or solvate thereof is in amorphous state or at least 90% of the olaparib is in amorphous state or at least 85% of the olaparib is in amorphous state.
In another aspect the present invention relates to method of treating cancer such as breast and ovarian cancer in the patient comprising administration to a patient in need thereof of a therapeutically effective amount of a formulation comprising olaparib or a pharmaceutically acceptable salt or solvate thereof, in solid dispersion with one or more matrix polymers or mixture of polymers. In such aspects, the medicament may comprise from 10 to 1500 mg of olaparib, such as from 10 to 1000 mg and from 25-400 mg.
The term “Olaparib” as used in the context of the present specification relates to the free base form, acid form, salt form, polymorphic crystalline or amorphous form, solvates, ethers, esters, etc. The therapeutic effective dose of olaparib for the treatment is 10 to 1500 mg of olaparib, such as from 10 to 1000 mg and from 25-400 mg.
The term `polymer` as used herein, means a macromolecule composed of repeating structural units connected by covalent chemical bonds. The term encompasses linear and branched polymers, cyclic polymers such as cyclic oligosaccharides (including cyclodextrins), homopolymers and copolymers, whether natural, synthetic or semi-synthetic in origin.
In an embodiment suitable polymers for use in the invention include: copovidone, povidone hypromellose phthalate (hydroxypropylmethylcellulose phthalate, HPMCP), hypromellose acetate succinate (hydroxypropylmethylcellulose acetate succinate, HPMCAS), -2-hydroxypropyl-.beta.-cyclodextrin (HPBCD), hypromellose (hydroxypropylmethylcellulose, HPMC), polymethacrylates (poly(methacrylic acid, methyl methacrylate 1:1; poly(methacrylic acid, ethyl acrylate) 1:1), hydroxypropyl cellulose (HPC), and cellulose acetate phthalate (CAP).
Copovidone is a synthetic, linear, random copolymer of N-vinyl-2-pyrrolidone (VP) and vinyl acetate (VA) where the VA content is nominally 40% (but may vary, for example between 35-41%). The addition of vinyl acetate to the vinylpyrrolidone polymer chain reduces hygroscopicity and glass transition temperature (Tg) of the polymer relative to Povidone (polyvinyl pyrrolidone, PVP homopolymer). The K-value for copovidone is between 25 and 31, and since the K-value is calculated from the kinematic viscosity of a 1% aqueous solution, it is related to the average molecular weight of the polymer. The average molecular weight (Mw) ranges from about 24,000 to 30,000.
PVP or povidone is a hygroscopic, amorphous, synthetic polymer consisting of linear 1-vinyl-2-pyrrolidinone groups. As a binder, PVP is used in the concentration range of 0.5%–5% w/w. Different degrees of polymerization of PVP resulted in polymers of various molecular weights. It is generally characterized by its viscosity in aqueous solution relative to that of water and expressed as a K value in the range of 10–120. Povidones with K-values = 30 are manufactured by spray drying as spheres, whereas povidones with higher K-values are manufactured by drum drying as plates.
In one embodiment the pharmaceutical formulation of the present invention is one suitable for mucosal administration to a patient. In another embodiment a particular mucosal administration route is oral, e.g., a tablet or capsule, and the like.
The term “pharmaceutically acceptable excipients” include, but not limited to, one or more of rate controlling polymers, diluents, disintegrants, binders, lubricants, glidants, acidifying agent, alkalizing agent, stabilizers, surfactants, sweetener, film coating materials, plasticizers, pigments, opacifiers, coloring agents and the like.
Suitable fillers include, for example, lactose, sugar, starches, modified starches, mannitol, sorbitol, inorganic salts, cellulose derivatives (e.g., microcrystalline cellulose, cellulose), calcium sulphate, xylitol and lactitol.
Suitable diluents, may be selected from, but not limited to the group consisting of different grades of starches, such as maize starch, potato starch, rice starch, wheat starch, pregelatinized starch, fully Pregelatinized starch; cellulose derivatives, such as microcrystalline cellulose or silicified microcrystalline cellulose; sugar alcohols such as mannitol, erythritol, sorbitol, xylitol; monosaccharides like glucose; oligosaccharides like sucrose and lactose such as lactose monohydrate, lactose anhydrous, spray dried lactose or anhydrous lactose; calcium salts, such as calcium hydrogenphosphate; particularly preferably the fillers are selected from the group consisting of, microcrystalline cellulose, silicified microcrystalline cellulose, lactose monohydrate, spray dried lactose, and anhydrous lactose and the like.
Suitable disintegrants may be selected from, but not limited to the group consisting of carmellose calcium, microcrystalline cellulose carboxymethyl starch sodium, croscarmellose sodium (cellulose carboxymethyl ether sodium salt, crosslinked), starch, modified starch such as pregelatinized starch, starch derivatives such as sodium starch glycolate, crosslinked polyvinylpyrrolidone (crospovidone), and low-substituted hydroxypropyl cellulose, and disintegrating aids such as magnesium alumino-metasilicate and ion exchange resins like polacrilin potassium; particularly preferably the disintegrants are selected from the group consisting of sodium starch glycolate, croscarmellose sodium and crospovidone and the like.
Suitable binders may be selected from, but not limited to the group consisting of polyvinyl pyrrolidone (Povidone), polyvinyl alcohol, copolymers of vinylpyrrolidone with other vinyl derivatives (Copovidone), hydroxypropyl methylcellulose, methylcellulose, hydroxypropyl cellulose, carboxymethylcellulose powdered acacia, gelatin, gum tragacanth, pectin, wax binders, microcrystalline cellulose, guar gum, sodium alginate, carbomer such as Carbopol, polymethacrylates and pregelatinized starch, lactose starches, modified starches, sugars, and the like.
Suitable lubricants include, for example, magnesium stearate, magnesium lauryl stearate, sodium stearyl fumarate, stearic acid, calcium stearate, zinc stearate, potassium benzoate, sodium benzoate, myristic acid, palmitic acid, mineral oil, hydrogenated castor oil, medium-chain triglycerides, poloxamer, polyethylene glycol and talc.
Suitable glidants, may be selected from, but not limited to the group consisting of colloidal silica, hydrophobic colloidal silica and magnesium trisilicate, such as talc and the like.
Suitable surfactants as component can be selected from, but not limited to the group consisting of anionic surfactants, preferably sodium lauryl sulphate; polyethylene glycols (PEGs), preferably those PEGs having molecular weight in the range of about 2000 to 10000, more preferably PEG 3350, PEG 4000, PEG 6000, PEG 8000; 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. More preferably the surfactant is selected from the group consisting of sodium lauryl sulphate; PEG 3350, PEG 4000, PEG 600 or, PEG 8000 and preferably PEG 6000; Tween 20 or Tween 80; and esters of polyethylene glycol and fatty acids, most preferably sodium lauryl sulphate and PEG 6000 and in particular sodium lauryl sulphate and the like.
Suitable sweeteners may be selected from, but not limited to the group consisting of aspartame, saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin, and the like.
Suitable film-forming agents and coating materials, if used, may include, but are not limited to hydroxypropyl methylcellulose (Hypromellose), hydroxypropyl cellulose, polyvinyl alcohol, , methylcellulose, ethyl cellulose, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, shellac, liquid glucose, hydroxyethyl cellulose, polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinyl acetate such as copovidone & Plasdone S630, 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 ethyl ester and methacrylic acid methyl ester, and copolymers of acrylic acid and acrylic acid methyl ester and the like.
Suitable plasticizers, if used, may include, but are not limited to polyethylene glycol, diethyl phthalate and glycerol. Preference is given to polyethylene glycol and the like.
The pharmaceutical composition of the present specification is stable throughout the shelf life when the compositions is subjected to accelerated and long-term stability studies.
The following examples will further describe certain specific aspects and embodiments of the invention in greater details and are not intended to limit the scope of invention.

EXAMPLES
Example 1: Olaparib Solid dispersions.
Sr. No. Name of Ingredients Example 1a
Example 1b
Example 1c
Example 1d
Example 1e
Example 1f

%w/w %w/w %w/w %w/w %w/w %w/w
1 Olaparib (Crystalline) 24.15 24.15 24.15 24.15 24.15 24.15
2 Copovidone 42.27 42.27 55.55 45.9 42.3
3 Povidone K30 - 10.9 - - -
4 Povidone 17PF - - - - 13.3 33.33
5 Povidone K25 22.22
6 Colloidal Silicon Dioxide 1.0 1.8 0.9 0.9 0.9 0.9
Total 67.42 79.12 80.6 70.95 80.65 80.6
Extragranular
6 Mannitol 27.00 16.1 14.2 23.9 14.2 14.1
7 Colloidal Silicon Dioxide 0.9 0 0.9 0.96 0.96 1.0
8 Sodium Stearyl Fumarate 1.5 1.4 1.0 1.0 0.96 1.0
Core Tablet Weight 96.82 96.62 96.7 96.8 96.8 96.7
9 Opadry QS QS QS QS QS QS
Total Film Coated Tablet weight 100 100 100 100 100 100

Process:
1. All ingredients were dispensed as disclosed in the above examples
2. Sift all the ingredients of the intragranular material through the 24# ASTM.
3. Blend the sifted material of step 2 in double cone blender
4. Hot melt extrusion was performed on the premix obtained in step 3 with specified parameters and the extrudes were collected
5. The extrudes obtained in the step 4 were milled with suitable screen, blended and then compressed and coated

Example 2: Olaparib Solid dispersions by solvent Evaporation
Sr. No. Name of Ingredients Example 2a Example 2b
Example 2C

%w/w %w/w %w/w
1. Olaparib 21.8 20.40 21.2
2. Copovidone 19.6 - -
3. HP Beta Cyclodextrin 27.2
50.99 25.45
4. Kollidon K30 - - 25.45
5. Microcrystalline cellulose
21.8 13.60 16.97
6. Solvent (Ethanol/Water) QS QS QS
Total Intra 90.4 84.99 89.07
7. Microcrystalline cellulose - 2.72 6.3
8. Colloidal Silicon Dioxide - 0.82 0.9
9. Silicified MCC 5.8 - -
10. Sodium Stearyl Fumarate 0.9 0.83 0.8
Core Tablet Weight 97 89.36 97.07
11. Opadry QS QS QS
Total Film Coated Tablet weight 100 100 100

Process:
1. Solvents, polymers and olaparib were added in a round bottom flask and heated to get a clear solution
2. The solution of step 1 was spray dried on to diluent
3. Granules of the step 2 were dried, blended and lubricated
4. The lubricated granules of step 3 were compressed and coated

Example 3: Two phase solid dispersion of Olaparib
Ingredients % w/w
Solid Dispersion 1: Hot Melt Extrusion
1 Olaparib 12.1
2 Copovidone 21.5
3 Colloidal Silicon Dioxide 0.6
Solid Dispersion 2: Solvent Evaporation by Top Spray technique
4 Olaparib 12.1
5 HP beta cyclodextrin 30.3
6 Microcrystalline cellulose 12.1
7 Solvent QS
Extragranular Part
9 Mannitol 5.5
10 CCS 0.6
11 Sodium Stearyl Fumarate 1.0
12 Colloidal Silicon Dioxide 1.0
Total Core Weight 97
Film Coating
13 Opadry QS
Coated Tablets Weight 100

Process:
1. Solid dispersion 1 was prepared as per process described under example 1 and solid dispersion part 2 was prepared as described under example 2
2. Then the dispersion of step 1 was compressed and coated

Example 4:
The stability of the compositions as per the present specification was evaluated through accelerated stability studies. The composition prepared according to the formula and process of as described in above examples were subjected to stability study at 40 °C/75% RH. The compositions were found to be stable at accelerated conditions. Table 1 represents the study result data and Table 2 represents the dissolution study data
Table 1: Stability study data
Product Specification Example 2 Example 3
Tests
Condition NA Initial 40±2°C&75±5%RH
(6M) Initial 40±2°C&75±5%RH
(6M)
Assay 95-105% 99.9% 98.75% 100.21% 98.56%
Water Content NMT 7% 3.42% 4.22% 4.18% 3.90%
Total Degradation NMT 0.5% 0.083% 0.0543% 0.0522% 0.0517%

Table 2: Dissolution Study data:
Product Example 2 Example 3
Tests
Condition Initial 40±2°C&75±5%RH
(6M) Initial 40±2°C&75±5%RH
(6M)
Time Points (Mins) Mean %RSD Mean %RSD Mean %RSD Mean %RSD
(pH 6.8PB, 900ml, Basket, 100rpm) 5 1 25.1 2 37.2 6 12.1 7 16.5
10 13 8.9 14 10.9 25 3.4 26 4.9
15 27 6.8 29 6.7 42 2.5 44 3.2
30 62 7.4 66 3.2 82 1.9 84 1.0
45 86 7.0 91 2.4 95 0.7 97 1.1
60 95 3.3 99 0.9 95 0.7 97 1.1
90 96 1.8 99 0.9 95 0.7 97 1.2

,CLAIMS:We claim:
1. Solid dispersion compositions of olaparib or a pharmaceutically acceptable salt or solvate thereof comprising one or more polymers or mixture of polymers and pharmaceutically acceptable excipients.
2. The compostion as claimed in claim 1, wherein the polymers are selected from copovidone, hypromellose phthalate (hydroxypropylmethylcellulose phthalate, HPMCP), hypromellose acetate succinate, hydroxypropyl-.beta.-cyclodextrin (HPBCD), povidone, (polyvinyl pyrrolidone, PVP homopolymer), hypromellose (hydroxypropylmethylcellulose, HPMC), polymethacrylates (poly(methacrylic acid, methyl methacrylate 1:1; poly(methacrylic acid, ethyl acrylate) 1:1), hydroxypropyl cellulose (HPC), and cellulose acetate phthalate (CAP) and mixtures thereof.
3. The composition as claimed in claim 1, wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the ratio of olaparib to copovidone is present in the ratio of 1:0.5 to 1:1.5
4. The composition as claimed in claim 1, wherein the ratio of olaparib to povidone is present in the ratio of 1:0.9 to 1:3.
5. The composition as claimed in claim 1, wherein the ratio of olaparib to copovidone to HP ß cyclodextrin is present in the ratio of 1:0.9:1:3.
6. The composition as claimed in claim 1, wherein the total amount of olaparib in the composition is in the range of from 25mg to 250mg and wherein the copovidone and HP ß cyclodextrin is present in the ratio of 1:0.5 to 1:2
7. The Composition as claimed in Claim 1, wherein the matrix polymer is mixture of HP ß cyclodextrin and copovidone and the formulation further comprises a glidant, a filler, a lubricant, and polymers in combination with a dissolution enhancing agent.
8. A method of producing solid dispersion as claimed in claim 1, where in the method comprises:
(i) mixing a suitable amount of Olaparib or a pharmaceutically acceptable salt or solvate thereof with a desired amount of matrix polymer
(ii) increasing the temperature of the mixture to produce a melt; and
(iii) extruding the melt to produce a solid product.

9. A method of producing solid dispersion as claimed in claim 1, where in the method comprises:
(i) preparing solvent solution and olaparib or a pharmaceutically acceptable salt or solvate thereof
(ii) heating on oil bath to get a clear solution and spraying the clear solution on to the suitable fillers
(iii) and then drying the granules obtained followed by blending, lubrication, compression and coating.

10. The Composition as claimed in claim 1, wherein the solid dispersion is made by solvent evaporation or melt extrusion or or a combination of both.