Amorphous pharmaceutical formulations of olaparib

Abstract

The present invention relates to a stable oral pharmaceutical composition comprising an amorphous spray dried dispersion of an Olaparib through neutralized polymer prepared by a spray drying process. The present invention further relates to a stable amorphous form of Olaparib. The present invention is an oral immediate release composition comprising: spray dried dispersion of Olaparib with neutralized polymer, and exhibits uniform drug release under all of the various pH conditions, and a method for preparing same.

Description

[0001] AMORPHOUS PHARMACEUTICAL FORMULATIONS OF OLAPARIB

[0002] RELATED APPLICATION

[0003] This application claims the benefit of Indian Patent Application No. 202421040895 filed on May 27, 2024 which is hereby incorporated for reference.

[0004] FIELD OF THE INVENTION

[0005] The present invention relates to an amorphous spray dried dispersion of Olaparib through spray dried powder of an Eudragit® E PO. More specifically, the present invention further relates to a stable oral pharmaceutical composition comprises a spray dried dispersion of Olaparib, wherein the spray dried dispersion comprises neutralized Eudragit® E PO, that enhanced solubility. The invention also related to the method of preparation thereof. The oral pharmaceutical composition of the present invention provides uniform drug release under all of the various pH conditions.

[0006] BACKGROUND OF THE INVENTION

[0007] Olaparib is a FDA-approved targeted therapy for cancer. It is a PARP inhibitor, inhibiting poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include ovarian, breast, and prostate cancers. It is marketed in the form of capsules and tablet under the trade names Lynparza® and is chemically known as 4-3-(4-cyclopropanecarbonyl-piperazine-l-carbonyl)-4-fluoro-benzyl- 2H-phthalazin-l-one and has the following chemical structure of Formula (I),

[0008] Olaparib is a crystalline solid, is non-chiral and essentially neutral across the physiological pH range. It belongs to class 4 within the Biopharmaceutics Classification System (BCS) because of its poor solubility and moderate permeability. Due to low solubility in water, it has a low dissolution rate and as a result exhibits poor bioavailability. In 2017, the US FDA approved Lynparza (Olaparib) tablets as indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy.

[0009] Lynparza® is formulated as film coating tablet and are available in two dosage strength containing Olaparib lOOmg and 150mg.

[0010] Polymorphic form A, which is used in the Lynparza preparation, was characterized in patent application W02008047082. Patent application W02009050469 then described crystalline form L.

[0011] U.S. Pat. No. 8,475,842 discloses pharmaceutical formulation comprising 4-3-(4- cyclopropane carbonyl piperazine- l-carbonyl)-4-fluoro-benzyl-2H-phthalazin-l- one in a solid dispersion with a matrix polymer that exhibits low hygroscopicity and high softening temperature, i.e., higher than 100°C, prepared by hot-melt extrusion method, to improve its bioavailability. In addition, the invention of U.S. Patent No. 8,475,842 relates to the use of copovidone in a solid dispersion composition with 4-3-(4- cyclopropanecarbonyl-piperazine-l-carbonyl)-4-fluoro benzyl-2H- phthalazin-l-one. 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.

[0012] W02010041051 describes various approaches to increase solubility and bioavailability of Olaparib, a poorly water-soluble PARP inhibitor. The prior art evaluates multiple polymers and concludes that forming an amorphous solid dispersion (ASD) of Olaparib using polymers with low hygroscopicity and a high glass transition temperature (Tg) or melting point (Tm) — typically above 100°C — could be advantageous for maintaining physical stability and improving bioavailability. The evaluation data shows that Eudragit E100 solid dispersions prepared at 50% w / w drug loading showed the presence of crystalline drug immediately after preparation, which persisted after one month of storage under accelerated conditions (30°C / 60% RH), indicating inadequate stabilization of the amorphous form. In addition, the prior art relates to the use of copovidone in a solid dispersion composition with 4-[3-(4-cyclopropanecarbonyl-piperazine-l- carbonyl)-4-fhioro-benzyl]-2H-phthalazin-l-one for increasing the bioavailability and / or stability of the 4-[3-(4-cyclopropanecarbonyl-piperazine- 1 -carbonyl)-4-fluoro-benzyl] -2H- phthalazin- 1 -one. The author of this prior art after performing various test concluded that the solid dispersions of Compound 1 and copovidone may be particularly stable and homogeneous.

[0013] Literature reports indicate that dispersions produced with Eudragit E may exhibit significant crystallinity (e.g. see Qi et al. Int. J. Pharm. 354:158-167, 2008); and, in a comparative study, may be less chemically stable than solid dispersions produced using Povidone K25 (Dargel, E., Mielck, J.B. Acta Pharm. Technol. 35(4): 197-209. 1989).

[0014] 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. However, the describe prior art process result in composition with Olaparib shows hot-melt extrusion method, which is tedious and expensive.

[0015] EP3263095, discloses the solid dispersion of Olaparib using hydrophilic polymer preparation of 40-100 °C 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 (Olaparib: Eudragit El 00 and Olaparib: Eudragit E PO in ratio 1: 1 and 1:3, respectively), after being placed at 40° C and 75% RH for 10 days, an endothermic peak appeared in DSC, and the stability of the solid dispersion was poor in this invention.

[0016] A major problem with current solid dispersions of drugs is that while the dispersions may show enhanced bioavailability of the low-solubility drug if administered shortly after preparation, bioavailability typically decreases over time in a typical storage environment. Such solid dispersions are often physically unstable in that the drug present in the dispersion reverts to the crystalline form upon storage — particularly at elevated temperature and humidity. Accordingly, the dispersion cannot be used to provide proper dosing of the drug because the bioavailability of the drug changes over time.

[0017] Solubilization of a specific drug depends on its chemical structure and physical properties, therefore, whether any particular polymer will solubilize a specific drug is not necessarily predictable. It is often difficult and time-consuming to select polymers which achieve improved solubilization.

[0018] The inventors of the present invention have developed a stable amorphous form of Olaparib through the utilization of spray-dried powder of neutralized Eudragit® E PO in the preparation of an amorphous spray-dried dispersion (SDD) formulation. This approach provides a new opportunity to formulate a stable pharmaceutical composition of Olaparib with enhanced solubility. Surprisingly, the resulting composition not only improves the solubility of Olaparib but also achieves a pH-independent dissolution profile, thereby enabling consistent drug release across a wide pH range.

[0019] Given the therapeutic significance of Olaparib as an anticancer agent, there remains a need to develop novel processes and formulations that enhance its solubility and ensure its stability. The present invention addresses this need by providing a stable oral composition of Olaparib, characterized by pH-independent drug release and the ability to maintain the drug in its amorphous form.

[0020] OBJECT OF THE INVENTION

[0021] An object of the invention to provide a stable amorphous spray dried dispersion of Olaparib.

[0022] Another object of the present invention is to provide a process for preparing a spray dried dispersion of Olaparib in an amorphous form with enhanced solubility.

[0023] A further object of the present invention is to provide a stable oral pharmaceutical composition comprising Olaparib with enhanced solubility in the composition.

[0024] Yet, another object of the invention is to prepare a spray dried dispersion of Olaparib in an amorphous form for obtaining pH independent drug release.

[0025] Another object of the present invention is to provide a process for preparing a spray dried dispersion of an Olaparib in an amorphous form using spray dried powder of low glass transition temperature (Tg) polymer.

[0026] Another object of the present invention is to design a spray dried dispersion of Olaparib in amorphous form using spray dried powder of neutralized Eudragit® E PO.

[0027] Another object of the present invention is to provide a process for neutralizing Eudragit® E PO polymer.

[0028] Another object of the present invention is to provide a process for preparing a spray dried powder of neutralized Eudragit® E PO that dissolved under intestinal pH conditions as well as acidic conditions.

[0029] Another object of the invention is to provide a method for preparation of an amorphous spray dried solid dispersion of Olaparib by spray drying.

[0030] Another object of the invention is to provide an oral pharmaceutical composition comprising the amorphous spray dried dispersion of Olaparib.

[0031] Another object of the invention is to provide an oral pharmaceutical composition of Olaparib that exhibit a pH independent release profile.

[0032] Another object of the invention is to provide a dosage form comprising an amorphous spray dried dispersion of Olaparib prepared using neutralized Eudragit® E PO and one or more pharmaceutically acceptable excipient. In yet, another object of the invention is to develop a film coated tablet comprising amorphous spray dried dispersion of Olaparib using neutralized Eudragit® E PO and one or more pharmaceutically acceptable excipient.

[0033] BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1: PXRD data for amorphization of spray dried dispersion sample of Olaparib prepared with Olaparib: Neutralized Eudragit® E PO-at different time points after storage at 40° C and 75% RH - a) at Initial (0 day) and b) at 30 days.

[0035] Figure 2: PXRD data for amorphization of the spray dried dispersion sample of Olaparib prepared with - Olaparib: non neutralized Eudragit® E PO (1:3). Figure 3: PXRD data for amorphization of the spray dried dispersion sample of Olaparib prepared with - Olaparib: Kollidon K-30 (1:3). Figure 4: PXRD data for amorphization of the spray dried dispersion sample of Olaparib prepared with Olaparib: PEG 6000 (1:3). Figure 5: PXRD data for amorphization of the spray dried dispersion sample of Olaparib prepared with Olaparib: PEG 20000 (1:3). Figure 6: PXRD data for amorphization of the spray dried dispersion sample of Olaparib prepared with Olaparib: Soluplus (1:3).

[0036] DETAILED DESCRIPTION

[0037] Hereinafter, a preferred embodiment of the present invention will be described in detail. Prior to the description, it should be understood that various modifications are possible to the embodiments of the present invention, and it should be understood that the scope of the invention is not limited to the following embodiments. The embodiments are purposed to merely give better explanation of the invention to those ordinarily skilled in the art.

[0038] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments.

[0039] As used herein, the singular forms “a",” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises,” “comprising,” “includes” and / or “including,” when used herein, specify the presence of stated features, integers, steps, operations, elements and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or groups thereof.

[0040] As used herein, the term “composition or “formulation” or “dosage form”, as in pharmaceutical composition, is intended to encompass a drug product comprising Olaparib or its amorphous spray dried dispersion and other inert ingredient(s) (pharmaceutically acceptable excipients). Such pharmaceutical compositions are synonymous with “formulation” and “dosage form”. Pharmaceutical composition of the invention include, but is not limited to, granules, powder, tablet, capsule and the like. Preferably, the pharmaceutical composition refers to tablet.

[0041] The present invention relates to a stable oral pharmaceutical preparation containing an amorphous spray dried dispersion of Olaparib with pH independent solubility of the active ingredient.

[0042] An "amorphous " as used in the present invention means a state of solid substances exhibiting no definite crystalline structure when characterized using Powder x-ray diffraction (PXRD) technique. The formation of characteristic peak in the form of diffractogram is the indication of specific amorphous form formation and considered as a critical quality parameter.

[0043] An “amorphous spray dried dispersion” or a “spray dried dispersion” or “amorphization of the spray dried dispersion” in refers to the spray dried material obtained in an amorphous form through spray drying of active pharmaceutical ingredient API, polymer solution into dried form. The spray dried dispersion of the present invention comprises a low-solubility drug and at least one polymer.

[0044] As used herein, unless otherwise indicated, the terms “about” should be understood to mean within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system.

[0045] The term “pH-independenf ’ for purposes of the present invention is defined as having characteristics (e.g., dissolution) which are substantially unaffected by pH.

[0046] The term "stable," as used herein, refers to physical and chemical stability, wherein not NLT 80% drug release in 60 minutes at 40°C ± 2°C, 75 % ± 5% RH (relative humidity) for a period of six month and more particularly to the extent necessary for the use of the composition. Further the term “stable” as used herein in the relation to amorphous form refers to the amorphous form that is stable up on storage.

[0047] The present invention relates to a stable solid oral pharmaceutical composition containing Olaparib with enhanced solubility and pH independent drug release profile.

[0048] The present invention further relates to a process for the preparation of a stable solid oral pharmaceutical composition comprising Olaparib in an amorphous spray dried dispersion form. The process involves the preparation of a spray-dried dispersion of Olaparib with a suitable polymer in a solvent system and subsequent removal of the solvent by spray drying to obtain an amorphous powder.

[0049] According to one embodiment, the present invention relates to a process for the preparation of amorphous spray dried dispersion of Olaparib using suitable polymer with a low glass transition temperature, i.e. with Tg in the range from 40°C to 100°C, in a solvent, to enhanced solubility and to achieve pH independent dissolution of Olaparib.

[0050] The present invention provides an amorphous spray dried dispersion of Olaparib with a polymer having the glass transition temperature in the range from 40°C to 100°C, preferably from 45°C to 70°C. In some embodiments, the polymer with the glass transition temperature from 40°C to 100°C is selected from the group consisting of Eudragits, which belong to copolymers of methacrylic acid esters. Out of Eudragits, Eudragit® E PO are especially preferred, which are chemically copolymers based on dimethyl aminoethyl methacrylate, butyl methacrylate and methyl methacrylate in the ratio of 2: 1: 1.

[0051] Polymers suitable for the preparation of solid dispersion are differ in their physicochemical characteristics such as solubility in water, glass transition temperature (Tg), viscosity and the like. The inventor of the present invention performed a series of experiments to convert the drug into its amorphous form in order to achieved enhanced solubility using high hygroscopic and high softening temperature polymer like Kollidon K-30, and low hygroscopic and low softening temperature polymer like Eudragit® E PO, PEG 6000, PEG 20000 and Soluplus in the ration 1:3 each and surprisingly found Eudragit® E PO (Eudragit® EPO) tremendously enhance the solubility of API. However, Eudragit® E PO is pH dependent polymer which give desired Dissolution profile and Disintegration (DT) in only 0.1 N HCL (acidic medium) whereas in pH 6.8 phosphate buffer (basic medium) there is no drug release and DT remain intact. Based on this problem, the inventor of the present invention designed amorphous spray dried dispersions (SDD) of Olaparib using spray dried powder of neutralized Eudragit® E PO.

[0052] The present invention further relates to a method for preparing a spray dried powder of neutralized Eudragit® E PO comprising a step of dissolving Eudragit® E PO in IN HC1 and then removing the solvent using spray drying from the resulting solution of dispersion liquid.

[0053] The term "neutralized Eudragit® E PO " as used herein, therefore refers to the spray dried powder of Eudragit® E PO / HC1 where Eudragit® E PO neutralized using hydrochloric acid and can be dissolved under acidic as well as intestinal conditions i.e. pH 1.2 to 7.4. During the neutralization process of Eudragit® E PO, Olaparib may optionally be added in amount 1 part to 100 part of the total amount of Olaparib present in the composition. According to one embodiment, the present invention provides a method of neutralized Eudragit® E PO comprising dissolution of Eudragit® E PO in IN HCL.

[0054] According to one embodiment, the present invention provides a method of neutralized Eudragit® E PO comprising dissolution of Eudragit® E PO in mixture of IN HCL and purified water (predefine ratio 50:50).

[0055] In some embodiments, Eudragit® E PO is stirred in a mixture of IN HCL at a temperature in the range of 60°C to 70°C till clear solution obtained.

[0056] According to another embodiment, the present invention relates to process for preparing amorphous spray dried dispersion of Olaparib using suitable polymer in a solvent, prepared by spray-drying technique, wherein the solvent is selected from the group consisting of Methanol, Ethanol, Water, Acetone, IPA, mixture of suitable solvent.

[0057] In preferably embodiment, the present invention relates to process for preparing an amorphous spray dried dispersion of Olaparib, prepared by spray-drying technique, comprising: preparing a solution in which Olaparib, neutralized Eudragit® E PO and Methanol-water mixture are dissolved; and drying the solution.

[0058] In some embodiments, the spray dried dispersion having the Olaparib: polymer ratio is in the range from 1:0.5 to 1:10, preferably from 1: 1 to 1:4.

[0059] An amorphous spray dried dispersion of Olaparib prepared by the methods of the present invention exhibited pH independent dissolution of Olaparib and thus correlated to have enhanced solubility.

[0060] According to one embodiment, the spray dried powder of neutralized Eudragit® E PO comprise Olaparib in range 1 part to 100 parts of the total amount of Olaparib present in the composition, wherein the Eudragit® E PO with Olaparib prepared by dissolving Olaparib and Eudragit® E PO in IN HC1 or in combination of IN HCL and Methanol and then removing the solvent using spray drying from the resulting solution of dispersion liquid.

[0061] According to another embodiment, the spray dried powder of neutralized Eudragit® E PO comprise Olaparib in range of 1 part to 100 parts of total amount of Olaparib present in the composition, wherein the Eudragit® E PO with Olaparib prepared by dissolving Olaparib and Eudragit® E PO in mixture of IN HCL and water (50:50) and then removing the solvent using spray drying from the resulting solution of dispersion liquid.

[0062] According to another embodiment, the spray dried powder of neutralized Eudragit® E PO comprise Olaparib in range of 1 part to 100 parts of total amount of Olaparib present in the composition, wherein the Eudragit® E PO with Olaparib prepared by dissolving Olaparib and Eudragit® E PO in mixture of IN HCL and water (50:50) or methanol and then removing the solvent using spray drying from the resulting solution of dispersion liquid.

[0063] According to one embodiment, the spray dried powder of neutralized Eudragit® E PO comprise Olaparib in range 1 part to 100 parts, wherein the Eudragit® E PO with Olaparib prepared by dissolving Olaparib and Eudragit® E PO in combination of mixture of IN HCL and water and methanol and then removing the solvent using spray drying from the resulting solution of dispersion liquid.

[0064] According to another embodiment, a drug-polymer solution prepared in a common volatile organic solvent(s) is mechanically or pneumatically atomized into fine droplets followed by solvent evaporation at extremely fast rate using a drying gas inside a drying chamber and the solid particles formed are collected in a cyclone.

[0065] The method of preparing the neutralized Eudragit® E PO of the present invention is described in detail below: a) Solution was prepared by mixing 500 gm of IN HC1 and 500gm of Purified water, b) Added 60 gm Eudragit® E PO into solvent a by continues stirring, c) Kept stirring till solution became cleared, d) Solution obtained was spray dried at Inlet Temp: 90-100 °C, Product Temp: 50-55°C, Atomization: 1.0 - 2.0 (kg / cm2), Feed Pump: 7-10 ml / min., Aspirator: 65 -80 (Nm3 / hr), e) Spray dried powder of neutralized Eudragit® E PO were collected in the collection vessel.

[0066] The method of preparing pH independent amorphous spray dried dispersion of Olaparib is described in detail below. a) Preparation of complex solution of Olaparib, Polymer (Neutralized Eudragit E PO) and solvent, b) The prepared drug-neutralized Eudragit® E PO polymer solution, in the desired ratio, was spray dried using spray drying machine with suitable nozzle diameter, c) The solutions of step (a) were fed to the nozzle via peristaltic pump at Inlet temperature 80-110°C, product temperature 40-55°C, spray rate 5-15 g / min, Aspiration rate 65-85, atomization 1-2 kg / cm2, flow rate 5-15 ml / min. d) The solutions were sprayed as atomized spray’s by the force of compressed nitrogen, e) The solvents in the droplets were evaporated in the drying chamber (inlet temperature of 80-110°C), and; f) The spray dried products were collected in the amorphous form in collection vessel. The invention further provides the use of the amorphous spray dried dispersion of Olaparib prepared using neutralized Eudragit E® PO for the preparation of an immediate release oral pharmaceutical composition of Olaparib.

[0067] According to another embodiment of the present invention, there is provided a pharmaceutical solid composition of Olaparib SDD, wherein the SDD comprises Olaparib in an amount range from about 1 -99%, preferably from aboutl0-90 %, more preferably from 30-70% and most preferably from about 10-40 %, weight by weight of total weight of pharmaceutical composition.

[0068] According to another embodiment, the amount of active pharmaceutical ingredient as a ratio by weight to the polymer used in the present invention for preparing Olaparib containing spray dried dispersion is from 1: 1 to 1: 10.

[0069] In a preferred embodiment of the present invention, the amount of active pharmaceutical ingredient as a ratio by weight to the polymer used in the present invention for preparing Olaparib containing spray dried dispersion is from 1: 1 to 1:4.

[0070] According to another embodiment, the experimental PXRD pattern of spray dried dispersion (SDD) of Olaparib prepared using neutralized Eudragit® E PO confirm absence of crystalline phase.

[0071] According to one embodiment of the present invention, the oral pharmaceutical composition comprising amorphous spray dried dispersion of Olaparib and one or more pharmaceutically acceptable excipients are disclosed.

[0072] According to another embodiment of the present invention, the oral pharmaceutical composition comprising amorphous spray dried dispersion of Olaparib, wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipient. The pharmaceutically acceptable excipients include, but are not limited to, a diluent, a disintegrant lubricant, a glidant and a film coating material.

[0073] According to another embodiment of the present invention, the pharmaceutically acceptable excipients further optionally include one or following: a binder, an acidifying agent, an alkalizing agent, plasticizer, a pigment, an opacifier, a coloring agent and any other excipients known to those skilled in the art.

[0074] The combination of pharmaceutically acceptable excipients may also be used. The amount of excipient(s) employed will depend upon how much active agent is to be used. One excipient can perform more than one function. According to preferred embodiment of the present invention, the pharmaceutical composition comprising amorphous spray dried dispersion of Olaparib with one or more pharmaceutically acceptable excipient and then compressed into solid dosage form.

[0075] The pharmaceutical compositions of the present invention can be any solid dosage form for example, but not limited to, granules, tablets and capsules.

[0076] According to an embodiment of the present invention, the pharmaceutical tablet composition comprising an amorphous spray dried dispersion of Olaparib through neutralized Eudragit E® PO and one or more pharmaceutically acceptable excipient exhibits pH independent disintegration time of not more than 60 minutes.

[0077] According to an embodiment of the present invention, the pharmaceutical tablet is film coated tablet comprising an amorphous spray dried dispersion of Olaparib and one or more pharmaceutically acceptable excipient.

[0078] According to another embodiment of the present invention, there is provided pharmaceutical solid composition of Olaparib SDD, wherein the pharmaceutical excipients present in an amount range from about 1-99 %, preferably from about 10-90 %, more preferably from about 15- 85 % and most preferably from about 20-80 %, weight by weight of total weight of the pharmaceutical composition. The total weight (or weight percent) of all the ingredients presents in the pharmaceutical composition add up to 100 wt %.

[0079] The diluent used in the pharmaceutical composition of the present invention is 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 or its commercial grade Perlitol SD 200, 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 hydrogen phosphate. The diluent is used either alone or in combination in the range of about 10% to 60%, weight by weight of total weight of the pharmaceutical composition.

[0080] The disintegrant used in the pharmaceutical composition of the present invention is selected from, but not limited to, 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, 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 the like. The disintegrant is used either alone or in combination in the range of about 2% to 15%, weight by weight of total weight of the pharmaceutical composition.

[0081] The lubricant used in the pharmaceutical composition of the present invention is selected from, but not limited to, 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. The lubricant is used either alone or in combination in the range of about 1% to 3%, weight by weight of total weight of the pharmaceutical composition.

[0082] The glidant used in the pharmaceutical composition of the present invention is selected from, but not limited to, the group consisting of colloidal silica, colloidal silicone dioxide or its commercial grade Aerosil 200, hydrophobic colloidal silica and magnesium trisilicate, such as talc and the like. The glidants is used either alone or in combination in the range of about 0.5% to 2.5%, weight by weight of total weight of the pharmaceutical composition.

[0083] The filler can be used in the pharmaceutical composition of the present invention is selected from, but not limited to, the group consisting of lactose, lactose monohydrate, spray dried lactose, anhydrous lactose sugar, starches, modified starches, mannitol, sorbitol, inorganic salts, cellulose derivatives (e.g., microcrystalline cellulose, cellulose), silicified microcrystalline cellulose, calcium sulphate, and the like xylitol and lactitol. The fillers may be used either alone or in combination in the range of about 10% to 60%, weight by weight of total weight of the pharmaceutical composition.

[0084] The binder can used in the pharmaceutical composition of the present invention, is selected from, but not limited to the group consisting of polyvinyl alcohol, 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. The binder may be used either alone or in combination in the range of about 1% to 5%, weight by weight of total weight of the pharmaceutical composition.

[0085] The film-forming agent and coating material used in the pharmaceutical composition of the present invention, is selected from, but not limited to, hydroxypropyl methylcellulose (Hypromellose), hydroxypropyl cellulose, polyvinyl alcohol, Opadry Green, methylcellulose, ethyl cellulose, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, shellac, liquid glucose, hydroxyethyl cellulose, copolymers of acrylic and / or methacrylic acid esters with trimethyl ammonium ethylacrylate, copolymers of dimethyl amino methacrylic 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. The film-forming agents is used either alone or in combination in the range of about 3% to 5%, weight by weight of total weight of the pharmaceutical composition.

[0086] The plasticizer can be used in the pharmaceutical composition of the present invention, is selected from, but not limited to, polyethylene glycol, diethyl phthalate and glycerol. The plasticizer may be used either alone or in combination, typically in the range of about 0.5 % to 1.0% weight by weight of total weight of the pharmaceutical composition.

[0087] According to an embodiment, the oral pharmaceutical composition of the present invention is stable. In an embodiment, the present invention relates to an oral pharmaceutical composition, wherein the said composition is stable for at least 6 month or to the extent necessary for the use of the composition upon storage at 40°C ± 2°C, 75 % ± 5% RH.

[0088] According to an embodiment, comparative dissolution study was conducted between the pharmaceutical composition of the present invention which comprise Neutralized Eudragit® E PO and pharmaceutical composition prepared in similar manner using non neutralized Eudragit® E PO.The study was performed across different pH using 0.1 N HCL, pH 4.5 Acetate Buffer, and pH 6.8 Phosphate Buffer.The dissolution profile was determined using using 900 ml of dissolution media, Apparatus 1 USP Basket at rotation speed of 100 RPM for 60 min. The results obtained are presented in Table 11(a) and 11(b) of Example 11.

[0089] According to another embodiment, the immediate release dosage form of the present invention release drug independent from the pH environment.

[0090] According to another embodiment, the immediate release dosage form of the present invention provides uniform drug release in 0.1N HC1, pH 4.5 Acetate buffer and pH 6.8 Phosphate buffer, indicating that the drug release from the dosage form is independent of pH variation. In contrast, the drug release from the non-neutralized tablet of Example 10 is pH dependent, showing equivalent drug release only in an acidic medium i.e. 0.1N HC1, with very low or no release in pH 4.5 and pH 6.8 buffer, which indicates that the pH dependant release behaviour is due to the non-neutralized Eudragit polymer (Eudragit EPO) used in the formulation. According to an embodiment, the pharmaceutical composition of the present invention comprises Neutralized Eudragit® E PO provide more than 90% of drug release in 60 minutes in all studied media i.e. 0.1 N HCL, pH 4.5 Acetate Buffer, and pH 6.8 Phosphate Buffer.

[0091] In yet another embodiment, the immediate release dosage form of the present invention provides more than 90% of drug release in 60 minutes in all studied media i.e. 0.1 N HCL, pH 4.5 Acetate Buffer, and pH 6.8 Phosphate Buffer.

[0092] In an embodiment, comparative disintegration study was conducted between the pharmaceutical composition of the present invention which comprise neutralized Eudragit® E PO and pharmaceutical composition prepared in similar manner using non neutralized Eudragit® E PO. The results obtained are presented in Table 12 of Example 12.

[0093] A spray dried dispersion of Olaparib, prepared by the method of the present invention, has increased dissolution rate, faster disintegration, and good stability with use of neutralized Eudragit® E PO. That is, the present invention provides a method for preparing an Olaparib containing spray dried dispersion that can release Olaparib without change according to the stomach condition of an individual (for example, dietary condition, food, and disease) because its disintegration, solubility and dissolution rate are not changed in extensive pH range.

[0094] According to another embodiment, comparative dissolution studies were conducted between the pharmaceutical composition of the present invention and commercially available Lynpraza® of similar strengths. These studies were performed across different pH conditions i.e., at pH 1.2, pH 4.5, and pH 6.8.

[0095] According to an embodiment, the pharmaceutical composition of the present invention provides drug release when measured in 900 mL buffer having 1.2 pH, Acetate buffer of 4.5 pH, and phosphate buffer of 6.8 pH compared with the commercially available Lynpraza® in such a way that: a) about 40% or more of total Olaparib releases within 30 minutes of measurement in said apparatus, b) about 75% or more of total Olaparib releases within 45 minutes of measurement in said apparatus, and; c) about 90% of total Olaparib releases within 60 minutes of measurement in said apparatus.

[0096] According to preferable embodiment, the pharmaceutical composition of the present invention releases at least 80% of Olaparib within 60 minutes. According to preferable embodiment, the pharmaceutical composition of the present invention releases at least 80% of Olaparib within 45 minutes.

[0097] In yet another embodiment, the immediate release dosage form of the present invention provides comparable drug release to the commercially available Lynpraza®.

[0098] According to another embodiment, the immediate release film coated dosage form of the present invention provides equivalent drug release in all three tested pH environments for each strength.

[0099] 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.

[0100] Example 1: Screening of polymer

[0101] Amorphous spray dried dispersions of poorly soluble Olaparib in polymers, including Eudragit® E PO (non- neutralized), Kollidon K-30, PEG and Soluplus, were investigated, aiming to identify the optimal polymer to enhance its solubility and stability of the drug product.

[0102] The aim of this work is to develop an spray dried dispersion of Olaparib for preparing stable amorphous formulation.

[0103] The production of amorphous spray dried dispersions of Olaparib through different Olaparib- polymer complex in ratio 1:3 (Table 1 and Figures 2-6) were assessed by recording the PXRD patterns.

[0104] The results are shown in below table:

[0105] Table 1: PXRD Data of Olaparib: polymer

[0106] The PXRD pattern of the Olaparib: Eudragit® E PO (non-neutralized) , as shown by figure 2, shows that spray dried dispersion of Olaparib in a non -neutralized Eudragit® E PO converts the compounds into an amorphous form. Example 2: Manufacturing Process of Neutralized Eudragit® E PO

[0107] Table 2: Neutralized Eudragit® E PO

[0108] Step by Step Process: 1. Dispensed the required quantity of Eudragit® E PO, purified water and IN HCL.

[0109] 2. Added Eudragit® E PO in mixture of IN HCL and purified water (predefine ratio 50:50) under stirring.

[0110] 3. Stirred the solution of step 2 for 45-60 minutes to get clear solution.

[0111] 4. Sprayed the solution of step 3 using spray dryer at Inlet Temp: 90-100 °C, Product Temp: 50-55°C, Atomization: 1.0 - 2.0 (kg / cm2), Feed Pump: 7-10 ml / min., Aspirator: 65 -80

[0112] (Nm3 / hr).

[0113] 5. Collected the spray dried powder and dried in the hot air oven at 60°C for 2-3 hr. Collect the dried materials and used as a spray dried powder of Neutralized EPO.

[0114] Example 3: Manufacturing Process of Neutralized Eudragit® E PO with presence of Olaparib

[0115] Table 3: Neutralized Eudragit® E PO containing Olaparib

[0116] Step by Step Process:

[0117] 1. Dispensed the required quantity of Eudragit® E PO, Olaparib, purified water, methanol and IN HCL. 2. Added Eudragit® E PO and Olaparib (1 part to 100 part) in mixture of IN HCL and purified water (predefine ratio 50:50) and methanol under stirring.

[0118] 3. Stirred the solution of step 2 for 45-60 minutes to get clear solution.

[0119] 4. Sprayed the solution of step 3 using spray dryer at Inlet Temp: 90-100 °C, Product Temp: 50-55°C, Atomization: 1.0 - 2.0 (kg / cm2), Feed Pump: 7-10 ml / min., Aspirator: 65 -80 (Nm3 / hr).

[0120] 5. Collected the spray dried powder and dried in the hot air oven at 60°C for 2-3 hr. Collect the dried materials and used as a spray dried powder of Neutralized EPO.

[0121] Example 4: An Oral Pharmaceutical Compositions of Olaparib prepared using Olaparib SDD comprising Neutralized Eudragit® E PO

[0122] Table 4: An Oral Pharmaceutical Compositions of Olaparib with Neutralized Eudragit® E PO.

[0123] Manufacturing process:

[0124] 1. Neutralized Eudragit® E PO powder and Olaparib dissolved in methanol: water under stirring at solution temperature of 60-70°C

[0125] 2. The solution of step 1 was spray dried at Inlet temperature 80-110C, product temperature 40-55°C, spray rate 5-15 g / min, Aspiration rate 65-85, atomization 1-2 kg / cm2, flow rate 5-15 ml / min and collected SDD.

[0126] 3. Obtained SDD dried in oven at 60°C for 2 hrs.

[0127] 4. Prepared SDD blended with fillers, disintegrant and glidant as per composition given above.

[0128] 5. Blend of step 4 lubricated using lubricant as mentioned in above composition.

[0129] 6. Lubricated blend compressed using suitable punches. 7. Film-Coating performed on Tablet using following process:

[0130] 7.1 Dissolved Opadry green in Purified Water (15%w / w solid content).

[0131] 7.2 Stirred the coating solution for 45 mins.

[0132] 7.3 Performed the Preheating of tablets for 5 -10 minutes at Inlet air temperature (60- 65°C), Inlet air flow (CFM): 1200-1350, Pan Speed rpm: 05-08.

[0133] 7.4 Performed the coating of tablets at Inlet air temperature (60-65°C), Inlet air flow (CFM): 2000-2500, Outlet air flow (CFM): 2505-2799, Pan Speed rpm: 10-20 and Product temperature: 35-45°C, Atomization pressure (bar): 0.8-1.0.

[0134] 7.5 Performed the drying of coated tablet for 5-10 minutes at Inlet air temperature (50- 55°C) / Inlet air flow (CFM): 1200-1350, Pan Speed rpm: 03-08.

[0135] Example 5: An Oral Pharmaceutical Compositions of Olaparib prepared using Olaparib SDD comprising Neutralized Eudragit E PO.

[0136] Table 5: An Oral Pharmaceutical Compositions of Olaparib with Neutralized Eudragit E PO.

[0137] Example 6: An Oral Pharmaceutical Compositions prepared using Olaparib SDD comprising Neutralized Eudragit® E PO

[0138] Table 6: An Oral Pharmaceutical Compositions of Olaparib comprising Neutralized Eudragit® E PO

[0139] Manufacturing Process:

[0140] The manufacturing process for Example 5 and Example 6 (I, II, and III) is the same as that of Example 4.

[0141] Example 7: An Oral Pharmaceutical Compositions prepared using Olaparib SDD comprising Neutralized Eudragit® E PO containing Olaparib

[0142] Table 7: An Oral Pharmaceutical Compositions using Olaparib SDD comprising Neutralized Eudragit® E PO containing Olaparib

[0143] Manufacturing process:

[0144] 1. Neutralized Eudragit® E PO powder with presence of Olaparib Ipart to 100 part was prepared according to process of example 3.

[0145] 2. Neutralized Eudragit® E PO powder of step 1 and remaining Olaparib (0% to 99%) dissolved in mixture of methanol: water under stirring at solution temperature of 60-70°C

[0146] 3. The solution of step 2 was spray dried at inlet temperature 80-110 °C, product temperature 40-55°C, spray rate 5-15 g / min, aspiration rate 65-85, atomization 1-2 kg / cm2, flow rate 5-15 ml / min and collected SDD.

[0147] 4. Obtained SDD dried in oven at 60°C for 2 hrs.

[0148] 5. Prepared SDD blended with fillers, disintegrant and glidant as per composition given above.

[0149] 6. Blend of step 5 lubricated using lubricant as mentioned in above composition.

[0150] 7. Lubricated blend compressed using suitable punches.

[0151] 8. Film-Coating performed on Tablet using following process:

[0152] 8.1 Dissolved Opadry green in Purified Water (15 %w / w solid content).

[0153] 8.2 Stirred the coating solution for 45 mins.

[0154] 8.3 Performed the Preheating of tablets for 5 -10 minutes at Inlet air temperature (60- 65°C), Inlet air flow (CFM): 1200-1350, Pan Speed rpm: 05-08.

[0155] 8.4 Performed the coating of tablets at Inlet air temperature (60-65°C), Inlet air flow (CFM): 2000-2500, Outlet air flow (CFM): 2505-2799, Pan Speed rpm: 10-20 and Product temperature: 35-45°C, Atomization pressure (bar): 0.8-1.0.

[0156] 8.5 Performed the drying of coated tablet for 5-10 minutes at Inlet air temperature (50- 55°C) / Inlet air flow (CFM): 1200-1350, Pan Speed rpm: 03-08.

[0157] Example 8: An Oral Pharmaceutical Compositions of Olaparib using Olaparib SDD comprising Neutralized Eudragit® E PO containing Olaparib

[0158] Table 8: An Oral Pharmaceutical Compositions of Olaparib using Olaparib SDD comprising Neutralized Eudragit® E PO containing Olaparib Example 9: An Oral Pharmaceutical Compositions of Olaparib using Olaparib SDD comprising Neutralized Eudragit® E PO containing Olaparib

[0159] Table 9: An Oral Pharmaceutical Compositions of Olaparib using Olaparib SDD comprising Neutralized Eudragit® E PO containing Olaparib

[0160] Manufacturing process:

[0161] The manufacturing process for Example 8 and 9 (I, II, and III) is the same as that of Example 7.

[0162] Example 10: An Oral Pharmaceutical Compositions using Olaparib SDD comprising Non- Neutralized Eudragit® E PO Table 10: An Oral Pharmaceutical Compositions of Olaparib

[0163] Manufacturing Process: 1. Eudragit® E PO powder (Non-Neutralized) and Olaparib dissolved in methanol: water under stirring at solution temperature of 60-70°C.

[0164] 2. The solution of step 1 was spray dried at Inlet temperature 80-1 IOC, product temperature 40-55°C, spray rate 5-15 g / min, Aspiration rate 65-85, atomization 1-2 kg / cm2, flow rate 5- 15 ml / min and collected SDD.

[0165] 3. Obtained SDD dried in oven at 60°C for 2 hrs.

[0166] 4. Prepared SDD blended with fillers, disintegrant and glidant as per composition given above.

[0167] 5. Blend of step 4 lubricated using lubricant as mentioned in above composition.

[0168] 6. Lubricated blend compressed using suitable punches.

[0169] 7. Film-Coating performed on Tablet using following process:

[0170] 7.1 Dissolved Opadry green in Purified Water (15%w / w solid content).

[0171] 7.2 Stirred the coating solution for 45 mins.

[0172] 7.3 Performed the Preheating of tablets for 5 -10 minutes at Inlet air temperature (60-65°C), Inlet air flow (CFM): 1200-1350, Pan Speed rpm: 05-08

[0173] 7.4 Performed the coating of tablets at Inlet air temperature (60-65°C), Inlet air flow (CFM): 2000-2500, Outlet air flow (CFM): 2505-2799, Pan Speed rpm: 10-20 and Product temperature: 35-45°C, Atomization pressure (bar): 0.8-1.0,

[0174] 7.5 Performed the drying of coated tablet for 5-10 minutes at Inlet air temperature (50-55°C) / Inlet air flow (CFM): 1200-1350, Pan Speed rpm: 03-08.

[0175] Example 11: Comparative Dissolution study between Example-6 (Neutralized Eudragit® E PO) and of Example- 10 (Non- Neutralized Eudragit® E PO) Olaparib Formulations in dissolution media of varying pH

[0176] The formulation of Example-6 (I) (Neutralized Eudragit® E PO) was subjected to comparative dissolution study with formulation of Example- 10 (Non- Neutralized Eudragit® E PO) using 0.1 N HCL, pH 4.5 Acetate Buffer, and pH 6.8 Phosphate Buffer. In vitro dissolution test carried out in 900 ml of dissolution media, Apparatus 1 USP Basket at 100 rpm for 60 min and the results obtained are presented in Table 8(a) and Table 8(b).

[0177] Table 11 (a): Drug Release Profile of Neutralized Eudragit® E PO containing Olaparib Formulation

[0178] Table 11 (b): Drug Release Profile of Non- Neutralized Eudragit® E PO containing Olaparib formulation

[0179] Observation & conclusion: The pharmaceutical composition of the present invention provides more than 90% drug release in 60 minutes compare to pharmaceutical composition of Olaparib comprising non-neutralized Eudragit® E PO formulation of example 10 where more than 90% drug release observed in only 0.1N HC1 and very low or no release observed in pH 4.5 Acetate buffer and pH 6.8 Phosphate buffer.

[0180] The dissolution results of Table 11 (a) and 11 (b) shows that Olaparib formulation of Example 6 shows more than 90% drug release in 60 minutes in all studied media compare to example 10 formulation where more than 90% drug release observed in only 0.1N HC1 and very low or no release observed in pH 4.5 Acetate buffer and pH 6.8 Phosphate buffer. The result indicates that example 6 formulation manufactured with neutralized Eudragit® E PO shows uniform drug release in all media compare to formulation of an Olaparib comprising non- neutralized Eudragit® E PO (example 10).

[0181] Accordingly, the improve pH independent release of the oral pharmaceutical composition of present invention attribute to neutralized Eudragit® E PO.

[0182] Example 12: Comparative Disintegration study between Example-6 (Neutralized Eudragit® E PO) and of Example-10 (Non- Neutralized Eudragit® E PO) Olaparib Formulations in buffer of varying pH

[0183] Table 12: Comparative Disintegration data

[0184] The pharmaceutical composition of Example 10 comprising non- neutralized Eudragit® E PO show much slower disintegration compared to the pharmaceutical composition of Example 6 comprising neutralized Eudragit® E PO in 0.1NHCL, pH 4.5 Acetate buffer & pH 6.8 Phosphate Buffer. The pharmaceutical composition of Example 10 comprising non- neutralized Eudragit® E PO remain intact in pH 4.5 acetate buffer and pH 6.8 Phosphate buffer.

[0185] Accordingly, the oral pharmaceutical compositions prepared using Olaparib SDD comprising Non-Neutralized Eudragit® E PO indicate resistance to disintegration at high pH.

[0186] Example 13: Stability Study of the Amorphous form of Olaparib SDD using Neutralized Eudragit® E PO

[0187] The resulting sample of the amorphous spray dried dispersion of Olaparib prepared using Neutralized Eudragit® E PO powder according to the process of Example 6 was assessed by PXRD (Measurements were conducted with X ray generator at 45 kV and 100 mA across a 29 range of 2°-50°, scan rate was 28.60° min-1, step width of 0.03, detector is D / tex Ultra 250), immediately after preparation and after storage for up to 1 month at 40° C and 75% RH (Figure 1 a and 1 b).

[0188] The study conducted in open petri plates. The stability study result shows that the amorphous form remain stable upon storage; for example, it does not change its description and PXRD pattern when stored under ambient conditions for at least for 30 days.

[0189] Example 14: Stability study data

[0190] The stability of the test sample of Example 6 (I) composition as per the present specification is evaluated through accelerated stability studies. The composition prepared according to the formula and process of as described in above example 6(1) are subjected to stability study at 40 °C / 75% RH. Table 13: Stability study data of the pharmaceutical composition of Olaparib 150mg (Example 6 (I)) at 40±2°C&75±5%RH

[0191] Conclusion: The stability data of the pharmaceutical composition of the present invention demonstrate that the present invention is stable for at least 6 months for the use of the composition upon storage at 40°C ± 2°C and 75 % ± 5% relative humidity (RH). The disintegration and dissolution characteristics remain within the acceptable limits throughout this storage period, supporting the suitability of the composition for continued use.

[0192] In conclusion, as is shown by the data in Tables 12 and 13 above and in Figures 1, the powder X- ray diffraction patterns of the compound / polymer(s) complexes obtained shows that dispersion of poorly soluble Olaparib in a neutralized Eudragit® E PO according to the present invention converts the compounds into a stable amorphous form and maintains excellent stability.

[0193] Example 15: Comparative Dissolution Study of RLD vs Formulation of Olaparib Using Neutralized Eudragit® E PO in dissolution media of varying pH

[0194] The test samples of formulation of Example 6, 150 mg (Neutralized Eudragit® E PO batch), were subjected to comparative dissolution study with LYNPRAZA® 150 mg film coated tablet (RLD), respectively at pH 1.2, pH 4.5, and pH 6.8. In vitro Dissolution test carried out in Apparatus 1 USP, Basket at 100 rpm, in 900 ml of dissolution media for 60 min and the results obtained are presented in below table:

[0195] Table 14(a): Comparative Drug Release Profile of LYNPRAZA® 150mg And Test 150mg ( Neutralized Eudragit® E PO batch )at pH 1.2.

[0196] Table 14(b): Comparative Drug Release Profile of LYNPRAZA® 150mg And Test 150 mg at pH 4.5

[0197] Table 14(c): Comparative Drug Release Profile of LYNPRAZA® 150mg And Test 150mg at pH 6.8

Claims

Claims,1. An immediate release solid oral pharmaceutical composition of Olaparib comprising: a) an amorphous spray dried dispersion; and b) one or more pharmaceutical excipients; wherein the amorphous spray dried dispersion comprises an Olaparib with a spray dried powder of a neutralized polymer.

2. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the spray dried dispersion comprising about 10 % to 40 % (w / w) of Olaparib.

3. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the spray dried powder of neutralized polymer comprises Eudragit® E PO polymer.

4. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim3, wherein the method to prepare the spray dried powder of neutralized Eudragit® E PO polymer comprising the following steps:

1. Dispensed the required quantity of Eudragit® E PO, purified water and IN HCL;2. Added Eudragit® E PO in mixture of IN HCL and purified water (predefine ratio 50:50) under stirring;3. Stirred the solution of step 2 for 45-60 minutes to get clear solution;4. Sprayed the solution of step 3 using spray dryer at Inlet Temp: 90-100 °C, Product Temp: 50-55°C, Atomization: 1.0 - 2.0 (kg / cm2), Feed Pump: 7-10 ml / min., Aspirator: 65 -80 (Nm3 / hr);5. Collected the spray dried powder and dried in the hot air oven at 60°C for 2-3 hr;6. Collected the dried materials and used as a spray dried powder of Neutralized EPO.

5. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim4, wherein the step of adding Eudragit® EPO in a mixture of IN HC1 and purified water (predefined ratio 50:50) under stirring is carried out in the presence of a portion of Olaparib, wherein the Olaparib is added in an amount corresponding to 1 part per 100 parts of the total Olaparib present in the composition, along with methanol.

6. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the weight ration of Olaparib to spray dried powder of neutralized polymer is in the range from 1: 1 to 1: 10.

7. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the method to prepare spray dried dispersion of Olaparib comprising the following steps: a) Preparation of complex solution of Olaparib, Polymer (Neutralized Eudragit E PO) and solvent; b) The prepared drug-Neutralized Eudragit® E PO polymer solution, in the desired ratio, was spray dried using spray drying machine with suitable nozzle diameter; c) The solutions of step a) were fed to the nozzle via peristaltic pump at Inlet temperature SOHO0®, product temperature 40-55°C, spray rate 5-15 g / min, Aspiration rate 65-85, atomization 1-2 kg / cm , flow rate 5-15 ml / min; d) The solutions were sprayed as atomized spray’s by the force of compressed nitrogen; e) The solvents in the droplets were evaporated in the drying chamber (inlet temperature of 80-110°C), and f) The spray dried products were collected in the amorphous form in collection vessel.

8. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the pharmaceutically acceptable excipients comprises diluents in amount 10% to 60%, disintegrants in amount 2% to 15%, lubricants in amount 1% to 3%, glidants in amount 0.5% to 2.5% and film coating materials 3% to 5% weight by weight of total weight of pharmaceutical composition.

9. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the solid oral pharmaceutical composition is in the form of tablet, granule and capsule.

10. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 9, wherein the tablet is immediate release film coated tablet.

11. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the pharmaceutical composition exhibit pH independent uniform drug releasewhen tested on Apparatus 1 USP, Basket at 100 rpm, in 900 ml of dissolution media of 0.1N HCL (hydrochloric acid), Acetate buffer pH 4.5 and phosphate buffer pH 6.8, at 100 RPM for 60 min.

12. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the composition exhibits a dissolution profile such that at least 80% of Olaparib is released within 45 minutes, wherein the release rate is measured on Apparatus 1 (USP, Basket) at 100 rpm.

13. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the pharmaceutical composition exhibits pH independent disintegration time of not more than 60 minutes.

14. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the oral pharmaceutical composition remain stable for at least 6 months when stored at 40°C ± 2°C and 75 % ± 5% .

15. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the oral pharmaceutical composition has a total impurity of less than 1% for at least 6 months when stored at 40°C ± 2°C and 75 % ± 5%.

16. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 1, wherein the amorphous spray-dried dispersion is characterized by a diffraction pattern by powder X ray diffraction (PXRD) that is absent of discrete peaks.

17. The immediate release solid oral pharmaceutical composition of Olaparib as claimed in claim 16, wherein no discrete peaks are detected by PXRD in the amorphous spray-dried dispersion when stored under ambient conditions for at least 30 days.

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