DESC:FIELD OF THE INVENTION:
The present invention relates to novel solid oral dosage pharmaceutical composition of olaparib or its pharmaceutically acceptable salt thereof and process for preparation thereof. The olaparib composition containing one or more matrix polymer provided by the present invention has an excellent in-vitro dissolution profile is safe and stable.
BACKGROUND OF THE INVENTION:
Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor used for the treatment of ovarian cancer, breast cancer, pancreatic cancer and prostate cancer. Olaparib is chemically known as 4-(3-(4-cyclopropanecarbonyl-piperazine- l-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-l-one and structurally, olaparib is represented as below:

OLAPARIB

Olaparib is disclosed in U.S. Patent No. 8475842 and is marketed under the brand name of Lynparza®, which is a film coated tablet, wherein the said patent discloses an immediate-release pharmaceutical composition of olaparib in the form of solid dispersion which is prepared by solvent evaporation (spray drying method) or hot melt extrusion, wherein the composition contains olaparib in an amorphous form, along with a matrix polymer as a copovidone polymer wherein the weight ratio of olaparib to polymer is in the range of from 1:2 to 1:4. US8475842 states that Povidone unexpectedly failed to provide a stable solid dispersion formulation for Olaparib and that 2. Solid dispersions produced using relatively hygroscopic polymer povidone tended to crystallize when stored at 40oC/75% relative humidity, leading to reduction in dissolution rate.
US20200108008 discloses an oral sustained and controlled release pharmaceutical composition of olaparib which contains a release rate adjusting matrix polymer as povidone for an improved dissolution form, wherein the composition is in the form of solid dispersion which contains olaparib, a matrix polymer as povidone and other additives such as surfactants, a lubricant, a colloidal silica, a plasticizer, and the like.

US10662178 discloses a pharmaceutical composition comprising a crystalline form of olaparib along with benzyl alcohol and one or more pharmaceutically acceptable excipient wherein the composition is in the form of tablet or capsule.
EP4079295 discloses an amorphous oral solid dispersion composition of olaparib wherein the composition contains a polymethacrylate copolymer wherein the polymethacrylate copolymer is poly (butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate).
CN104434809 discloses olaparib solid dispersion particles agent comprising Olaparib, povidone and lubricant compositions.
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.
The above prior art references disclose different compositions comprising Olaparib. Still, there exists a need for the development of alternate formulations comprising Olaparib. The inventors of the present invention have surprisingly found that a tablet composition comprising olaparib composition containing one or more matrix polymer. The present invention has an excellent in-vitro dissolution profile is safe and stable.
There is a need to provide oral solid dispersion compositions of olaparib which contains a matrix polymer with improved bioavailability, stability and drug loading when compared to other tablet composition of Olaparib. The present invention also relates to a process for preparing these novel pharmaceutical compositions.

SUMMARY OF THE INVENTION:
The present invention involves a solid dispersion composition of olaparib in the tablet form, wherein the composition contains olaparib, one or more matrix polymer and one or more pharmaceutically acceptable excipients.
In an embodiment, the present invention involves a solid dispersion composition of olaparib along with a matrix polymer, povidone including but not limited to Povidone K12, Povidone K90, Povidone K25, Povidone K30, povidone 12PF, povidone 17PF or povidone K25 and in another embodiment the weight ratio of olaparib to polymer is in the range of 1: =4.
In another embodiment, the present invention involves a solid dispersion composition of olaparib along a matrix polymer wherein the matrix polymer is a hydrophilic polymer with the glass transition temperature in the range from 40°C to 100°C, include, but not limited to a polyvinyl caprolactam / polyvinyl acetate /polyethylene glycol copolymer (soluplus) and/or copolymers based on dimethyl aminoethyl methacrylate, butyl methacrylate and methyl methacrylate and wherein the weight ratio of olaparib to polymer is in any range.
In another embodiment, the present invention involves a solid dispersion composition of olaparib along a matrix polymer include, but not limited to copovidone, hypromellose phthalate (hydroxypropylmethylcellulose phthalate, HPMCP), HPMC phthalate HP-50, HPMC E6, hypromellose acetate succinate (hydroxypropylmethylcellulose acetate succinate, HPMCAS), -2-hydroxypropyl -ß- 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) and wherein the weight ratio of olaparib to polymer is in any range.
In another embodiment, the solid dispersion composition of olaparib or its pharmaceutically acceptable salts thereof along with one or more pharmaceutically acceptable excipients include, but not limited to fillers, binders, disintegrants, lubricants, preservatives, stabilisers, anti-oxidants, silica flow conditioners, antiadherents, glidants, solubility enhancers and/or coating agents and/or colouring agents.
In another embodiment, the methods for preparing the solid dispersion composition of olaparib or its pharmaceutically acceptable salts thereof include, but not limited to aqueous granulation, kneading method, solvent evaporation, spray drying process, lyophilisation, supercritical fluid, co-precipitation and electrospinning.

BRIEF DESCRIPTION OF THE DRAWINGS:
Figure 1: illustrates in-vitro dissolution profile of the product of present invention with reference product (Lynparza® 150mg tablet) at 100 RPM in 900 mL of Phosphate buffer pH 6.8, Basket at (37 ± 0.5) ºC.

DETAILED DESCRIPTION OF THE INVENTION:
The nature of the invention is clearly described in the specification. The invention has various components and they are clearly described in the specification. The present invention will now be disclosed by describing certain preferred and optional embodiments, to facilitate various aspects thereof.
The present invention discloses a method for preparing solid dispersion comprising the steps of dissolving the drug and the polymer in a common solvent and evaporating the solvent. The solvent is judiciously selected according to the polymer used. Examples of solvents are: acetone, acetone/dichloromethane, methanol/dichloromethane, acetone/water, acetone/methanol, acetone/ethanol, dichloromethane/ethanol or ethanol/water. The methods for evaporating solvent include vacuum drying, spray drying, tray drying, freeze drying or other drying technique, rotary evaporation, lyophilization and thin film evaporation. Alternatively, solvent removal may be accomplished by cryogenic freezing followed by lyophilization.
In one aspect of the present invention, one or more fillers include, but not limited to lactose, sugar, starches, modified starches, mannitol, sorbitol, inorganic salts, cellulose derivatives (e.g. microcrystalline cellulose, cellulose), calcium sulphate, xylitol and lactitol.
In another aspect of the present invention, one or more channeling agent include, but not limited to mannitol, sodium chloride, sugars, polyol and EMDEX® (glucose monohydrate and different polysaccharides derived from starch).
In another aspect of the present invention, one or more binders include, but not limited to lactose, starches, modified starches, sugars, gum acacia, gum tragacanth, guar gum, pectin, wax binders, microcrystalline cellulose, methylcellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, copolyvidone, gelatine, polyvinylpyrollidone (PVP) and sodium alginate.
In another aspect of the present invention, one or more disintegrants include, but not limited to crosslinked polymers, including crosslinked polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose (croscarmellose sodium) and the modified starch sodium starch glycolate.
In another aspect of the present invention, one or more lubricants include, 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.
In another aspect of the present invention, one or more preservatives include, but not limited to sodium benzoate, EDTA, sorbic acid and parabens.
In another aspect of the present invention, one or more stabilizers include, but not limited to PVP (Povidone), PVA (Polyvinyl alcohol), PEG (Polyethylene glycol), HPMC (Hypromellose), HPC (Hydroxypropyl cellulose) and HEC (Hydroxyethyl cellulose).
In another aspect of the present invention, one or more anti-oxidants include, but not limited to butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS).
In another aspect of the present invention, one or more antiadherents include, but not limited to Tween®-80 (Polysorbate-80), sodium lauryl sulfate (sodium dodecyl sulfate), Labrafil® (PEGylated oils), and Labrasol® (PEGylated caprylic/capric glycerides).
In one aspect of the present invention, one or more glidants include, but not limited to talc, colloidal silicon dioxide, magnesium stearate, and silica.
In another aspect of the present invention, one or more solubility enhancer include, but not limited to magnesium aluminometasilicate, sepitrap 80 or any combinations thereof.
In another aspect of the present invention, one or more coating agents include, but not limited to Opadry, polyvinyl alcohol (PVA), Eudragit® EPO, hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), and polyvinyl alcohol-polyethylene glycol (PVA-PEG copolymer).
In another aspect of the present invention, one or more colouring agents include, but not limited to red ferric oxide, titanium oxide, lead oxide, copper sulfate and carbon black.
In another aspect of the present invention, olaparib or its pharmaceutically acceptable salts thereof is present in an amount of 10-50%, more preferably 15-45% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, the polymer in the composition is present in an amount of 1 to 95%, more preferably 2% to 85% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, one or more filler in the composition is present in an amount of 1 to 70%, more preferably 3 to 7% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, one or more binder in the composition is present in an amount of 2 to 40% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, one or more disintegrant in the composition is present in an amount of 1 to 20% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, one or more lubricant in the composition is present in an amount of 0.5 to 3%, more preferably 0.5 to 3% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, one or more preservative in the composition is present in an amount of 0.02 to 0.5% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, one or more stabiliser in the composition is present in an amount of 0.5 to 10% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, one or more anti-oxidant in the composition is present in an amount of 0.05 to 0.9% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, one or more anti-adherent in the composition is present in an amount of 5 to 20% by weight of the total weight of the pharmaceutical composition.
In another aspect of the present invention, one or more glidant in the composition is present in an amount of 0.5 to 3.0%, more preferably 0.5 to 1.5% by weight of the total weight of the pharmaceutical composition.

In another aspect of the present invention, one or more film coating agent in the composition is present in an amount of 1 to 3% by weight of the total weight of the pharmaceutical composition.
In another aspect, the present invention relates to a process for preparing solid oral composition of olaparib by spray drying technique:
a) preparing solid dispersion of olaparib with one or more matrix polymers by using solvent,
b) spray drying the solid dispersion of olaparib for the removal of solvents using a spray drying equipment,
c) sifting solid dispersion of olaparib through co-sift with fillers and glidant
d) sifting the lubricant,
e) pre-slugging the sifted material of step (c) into blender and lubricating the blend with lubricant of step (d),
f) slugging and de-slugging,
g) blending & lubricate with lubricant,
h) compressing into a tablet,
i) coating with coating agent in purified water to form a film coated tablet.
Inventors of the present invention have surprisingly arrived at better intact property of composition and improvement in release profile when mixture of one or more polymers are in ratio of 1: =4. The addition of one or more polymers preferably in ratio of 1:=4 for preparation for composition enhances the release profile and solubility and the dissolution profile was similar to reference product (Lynparza® 150mg tablet).
The term "oral" administration means that the active agent is in a formulation designed to be ingested, i.e. designed to be delivered to the gastrointestinal system for absorption.
The term "solid oral composition" comprises capsule, tablet (film coated tablet, controlled release tablet, modified release tablet, extended release, delayed release, immediate release etc.), micro tablet, powder, granule and pellets. Capsules used as oral dosage form can be soft or hard capsules, though oral dosage form of the present invention is tablet.
The term "% w/w" refers to the relative value to total weight of granules or to total weight of pharmaceutical composition and “%v/v” refer to volume by total volume percentage.
The pharmaceutical composition of the present specification is stable throughout the shelf life when subjected to accelerated and long-term stability studies.
The present invention has been described by way of example only. It is to be recognized that modifications falling within the scope and spirit of the claims, which would be obvious to a person skilled in the art based upon the disclosure herein, are also considered to be included within the scope of this invention. The scope of the invention is in no manner limited by the disclosed example.
EXAMPLE 1:
Table 1: Preparation of tablet containing Olaparib and Povidone K12 PF
(API to Polymer ratio – 1:4.5)
Sr. No. Ingredients Mg/Tablet %w/w
150 mg
Binder solution
1 Olaparib 150.00 18.18
2 Povidone K12 PF 675.00 81.82
3 Methanol q.s -
4 Dichloromethane q.s -
Total weight of dispersion 825.00 100.00
Intra-granular materials
5 Olaparib spray dried material 825.00 91.67
6 Mannitol (200 SD) 52.50 5.83
7 Colloidal silicon dioxide 9.00 1.00
Lubrication (Pre-slugging)
8 Sodium stearyl fumarate 4.50 0.50
Lubrication
9 Sodium stearyl fumarate 9.00 1.00
Total weight of coated tablet 900.00 100.00

EXAMPLE 2:
Table 2: Preparation of tablet containing Olaparib and Povidone K30
(API to Polymer ratio – 1:4.5)
Sr. No. Ingredients Mg/Tablet %w/w
150 mg
Binder solution
1 Olaparib 150.00 18.18
2 Povidone K30 675.00 81.82
3 Methanol q.s -
4 Dichloromethane q.s -
Total weight of dispersion 825.00 100.00
Intra-granular materials
5 Olaparib spray dried material 825.00 91.67
6 Mannitol (200 SD) 52.50 5.83
7 Colloidal silicon dioxide 9.00 1.00
Lubrication (Pre-slugging)
8 Sodium stearyl fumarate 4.50 0.50
Lubrication
9 Sodium stearyl fumarate 9.00 1.00
Total weight of coated tablet 900.00 100.00

EXAMPLE 3:
Table 3: Preparation of tablet containing Olaparib and Povidone K30 with Povidone K90 (API to Polymer ratio – 1:4.5)
Sr. No. Ingredients Mg/Tablet %w/w
150 mg
Binder solution
1 Olaparib 150.00 18.18
2 Povidone K30 658.12 79.77
3 Povidone K90 16.88 2.05
4 Methanol q.s -
5 Dichloromethane q.s -
Total weight of dispersion 825.00 100.00
Intra-granular materials
6 Olaparib spray dried material 825.00 91.67
7 Mannitol (200 SD) 52.50 5.83
8 Colloidal silicon dioxide 9.00 1.00
Lubrication (Pre-slugging)
9 Sodium stearyl fumarate 4.50 0.50
Lubrication
10 Sodium stearyl fumarate 9.00 1.00
Total weight of coated tablet 900.00 100.00
EXAMPLE 4:
Table 4: Preparation of tablet containing Olaparib and Povidone K30 with Povidone K90 (API to Polymer ratio – 1:4.5)
Sr. No. Ingredients Mg/Tablet %w/w
150 mg
Binder solution
1 Olaparib 150.00 18.18
2 Povidone K30 641.25 77.73
3 Povidone K90 33.75 4.09
4 Methanol q.s -
5 Dichloromethane q.s -
Total weight of dispersion 825.00 100.00
Intra-granular materials
6 Olaparib spray dried material 825.00 91.67
7 Mannitol (200 SD) 52.50 5.83
8 Colloidal silicon dioxide 9.00 1.00
Lubrication (Pre-slugging)
9 Sodium stearyl fumarate 4.50 0.50
Lubrication
10 Sodium stearyl fumarate 9.00 1.00
Total weight of coated tablet 900.00 100.00

EXAMPLE 5:
Table 5: Preparation of tablet containing Olaparib and Povidone K30 with Povidone K90 (API to Polymer ratio – 1:4.5)
Sr. No. Ingredients Mg/Tablet %w/w
150 mg
Binder solution
1 Olaparib 150.00 18.18
2 Povidone K30 641.25 77.73
3 Povidone K90 33.75 4.09
4 Methanol q.s -
5 Dichloromethane q.s -
Total weight of dispersion 825.00 100.00
Intra-granular materials
6 Olaparib spray dried material 825.00 91.67
7 Mannitol (200 SD) 52.50 5.83
8 Colloidal silicon dioxide 9.00 1.00
Lubrication (Pre-slugging)
9 Sodium stearyl fumarate 4.50 0.50
Lubrication
10 Sodium stearyl fumarate 9.00 1.00
Total weight of coated tablet 900.00 100.00

EXAMPLE 6:
Table 6: Preparation of tablet containing Olaparib and Povidone K30 with Povidone K90 (API to Polymer ratio – 1:4.0)
Sr. No. Ingredients Mg/Tablet %w/w
150 mg
Binder solution
1 Olaparib 150.00 20.00
2 Povidone K30 570.00 76.00
3 Povidone K90 30.00 4.00
4 Methanol q.s -
5 Dichloromethane q.s -
Total weight of dispersion 750.00 100.00
Intra-granular materials
6 Olaparib spray dried material 825.00 91.67
7 Mannitol (200 SD) 52.50 5.83
8 Colloidal silicon dioxide 9.00 1.00
Lubrication (Pre-slugging)
9 Sodium stearyl fumarate 4.50 0.50
Lubrication
10 Sodium stearyl fumarate 9.00 1.00
Total weight of coated tablet 900.00 100.00

EXAMPLE 7:
Table 7: Preparation of tablet containing Olaparib and Povidone K30 with Povidone K90 (API to Polymer ratio – 1:3.0)
Sr. No. Ingredients Mg/Tablet %w/w
150 mg
Binder solution
1 Olaparib 150.00 25.00
2 Povidone K30 427.00 71.25
3 Povidone K90 22.50 3.75
4 Methanol q.s -
5 Dichloromethane q.s -
Total weight of dispersion 825.00 100.00
Intra-granular materials
6 Olaparib spray dried material 825.00 91.67
7 Mannitol (200 SD) 52.50 5.83
8 Colloidal silicon dioxide 9.00 1.00
Lubrication (Pre-slugging)
9 Sodium stearyl fumarate 4.50 0.50
Lubrication
10 Sodium stearyl fumarate 9.00 1.00
Total weight of coated tablet 900.00 100.00

EXAMPLE 8:
Table 8: Preparation of tablet containing Olaparib and Povidone K30 with Povidone K90 (API to Polymer ratio – 1:4.0)
Sr. No. Ingredients Mg/Tablet Mg/Tablet %w/w
100 mg 150 mg
Binder solution
1 Olaparib 100.00 150.00 20.00
2 Povidone K30 380.00 570.00 76.00
3 Povidone K90 20.00 30.00 4.00
4 Methanol$ q.s q.s -
5 Dichloromethane$ q.s q.s -
Total weight of dispersion 500.00 750.00 100.00
Intra-granular materials
6 Olaparib spray dried material 500.00 750.00 92.59
7 Mannitol (200 SD) 25.00 37.50 4.63
8 Colloidal silicon dioxide 6.00 9.00 1.11
Lubrication (Pre-slugging)
9 Sodium stearyl fumarate 3.00 4.50 0.56
Lubrication
10 Sodium stearyl fumarate 6.00 9.00 1.11
Total Weight of Lubricated Blend 540.00 810.00 100.00
Film coating
11 Opadry AMB II 88ZA540003 Pink 12.15 18.23 -
12 Purified Water q.s q.s -
Total weight of coated tablets 552.15 828.23 -

DISSOLUTION STUDY
Dissolution rate is a critical property that is prerequisite for final dosage form Comparative dissolution profile of the product of present invention with a reference product was studied. It was found that dissolution of present invention vis-à-vis reference product was comparable. Complete release and hence, solubility enhancement was achieved
Dissolution study of the pharmaceutical dosage of the present invention was carried out by HPLC. The dissolution method employed in the present invention is USP Apparatus I with sinker at 100 RPM in 900 mL of Phosphate buffer pH 6.8, Basket at (37 ± 0.5) ºC. Samples were taken at 10, 15, 30, 45, 60 and 90 minutes. The sample was filtered through a 0.45 µm syringe filter, transferred to HPLC vials and analyzed by HPLC. Tablet 9 depicts the comparative dissolution data of the Olaparib tablet of reference product vis-à-vis the product of the present invention.
Table 9: Comparative dissolution study of Olaparib tablet of present invention with reference product
Test Reference product
Lynparza (Olaparib) 150 mg
Example 6 & 8
API: Povidone K30/K90 – (1:4.0) Example 4
API: Povidone K30/K90 – (1:4.5)
Time(min) % Drug Release % Drug Release % Drug Release
10 14.40 14.90 18.00
15 25.02 26.90 30.00
30 53.86 56.90 59.20
45 76.66 76.50 78.60
60 90.72 86.40 89.60
90 94.73 91.14 95.20
Rec 93.99 90.76 95.00
F2 -- 78.36 70.41
*Similarity factor: The F2 value between 50 and 100 establishes sameness of the two dissolution profiles. Physical parameters of tablets were found satisfactory. Uniform slow erosion during was observed up to 35 minutes.
STABILITY STUDY
The inventors of the present invention have surprisingly found that the Olaparib tablets of the present invention underwent rapid and complete dissolution initially compare to reference product. The Olaparib tablets of the present invention underwent rapid and complete dissolution even after 6 months when tested using the USP Apparatus (I) in comparison with the reference product of the innovator. An increase in the solubility and dissolution rates leads to consistent and uniform improvement in the bioavailability of the drug.
The composition in accordance with the present invention was subjected to stability studies under stability analysis condition of 40°C±2°C and relative humidity 75%±5%. Olaparib tablets of present invention are adequately stable, as per general stability requirement under conditions. Additionally, Olaparib tablets of present invention are also stable in accelerated stability conditions.
The present invention is storage stable at prolonged period of time. The composition is stable and the stability Study of film coated tablets with Povidone K30 & Povidone K90 (Ratio 1:4.0) is depicts in Table 10.
Table 10: Stability study of Olaparib tablet of the present invention
Stability station Initial 1 Month 3 Month 6 Month
Condition Initial 40°C/75%RH 40°C/75%RH 40°C/75%RH
Assay (%) 99.05 103.9 95.47 NA
Impurity 1 0.071 0.00 0.00 0.00
Impurity 2 ND 0.00 0.07 0.06
Impurity 3 ND 0.00 0.00 0.01
Single max unknown 0.03 0.04 0.04 0.04
Total
(NMT 2.0%) 0.16 0.17 0.25 0.26
Dissolution
pH 6.8,900 ml, Basket, 100 RPM, USP-I
92.40
90.80
90.34
93.22
*ND = Not detected

As indicated in above table, the result of the stability study establish that Olaparib composition in accordance with the present invention exhibits excellent storage stability.
The inventors of the present invention conducted disintegrating and dissolution studies with other polymers by Spray drying technique and found to be unsatisfactory. Satisfactory dissolution profile and solubility enhancement was not achieved as depicted below;
Table 11: Olaparib and Soluplus (API to Polymer ratio – 1:2.57)
Test Results
Assay 100.04%
Dissolution (Media for soft gel capsules of Olaparib)
Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL
Time (min) % Drug Release
30 5.68
60 10.89
Rec 19.63
Table 12: Olaparib and Soluplus with Polysorbate 80 (API to Polymer ratio – 1:1.5)
Test Results
Assay NA
Dissolution (Media for soft gel capsules of Olaparib)
Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL
Time (min) % Drug Release
30 21.73
60 37.77
Rec 73.44
Table 13: Olaparib and Soluplus with Polysorbate 80 (API to Polymer ratio – 1:2.25)
Test Results
Assay 95.45
Dissolution (Media for soft gel capsules of Olaparib)
Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL
Time (min) % Drug Release
30 30.92
60 43.49
Rec 55.59
Table 14: Olaparib and HPMC Phthalate HP-50 with Polysorbate 80 (API to Polymer ratio – 1:1.5)
Test Results
Assay 86.01
Dissolution (Media for soft gel capsules of Olaparib)
Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL
Time (min) % Drug Release
10 41.27
15 45.32
30 54.54
45 57.70
60 59.17
Rec NA
Table 15: Olaparib and HPMC with Polysorbate 80 (API to Polymer ratio – 1:1.5)
Test Results
Assay NA
Dissolution (Media for soft gel capsules of Olaparib)
Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL
Time (min) % Drug Release
10 33.60
15 45.41
30 68.23
45 77.70
60 81.62
Rec NA

Table 16: Olaparib and HPMC (API to Polymer ratio – 1:1.5)
Test Results
Assay NA
Dissolution (Media for soft gel capsules of Olaparib)
Phosphate buffer pH 6.8, Basket, 100 RPM, 900 mL
Time (min) % Drug Release
10 17.97
15 24.83
30 42.80
45 58.11
60 70.86
Rec NA
The invention described herein comprises in various objects as mentioned above and their description in relation to characteristics, compositions and process adopted. While these aspects are emphasised in the invention, any variations of the invention described above are not to be regarded as departure from the spirit and scope of the invention as described.
The above-mentioned examples are provided for illustrative purpose only and these examples are in no way limitative on the present invention.

We claim:
1. A solid oral composition comprising Olaparib and hydrophilic matrix polymer in the ratio of 1: =4.

2. A solid oral composition as claimed in Claim 1 comprising
a) 10 to 50% w/w of solid dispersion of Olaparib,
b) 1 to 95% w/w of matrix polymer or a mixture thereof,
c) 0.5 to 3% w/w of lubricant or a mixture thereof,
d) 0.5 to 3% w/w of glidant,
e) 1 to 10% w/w of channelling agent
f) 1 to 3% w/w of film coating agent
g) solvent or a mixture thereof, and optionally other excipients.

3. The solid oral composition as claimed in claim 1, wherein the total amount of Olaparib in the composition is in the range of from 25mg to 250mg.

4. The solid oral composition as claimed in claim 1, wherein the hydrophilic polymers matrix is selected from Povidone K12, Povidone K90, Povidone K25, Povidone K30, Povidone 12PF, Povidone 17PF or Povidone K25 or a mixture thereof preferably 2% to 85% w/w by weight of the total weight of the pharmaceutical composition.

5. The solid oral composition as claimed in claim 1, wherein the lubricant is selected from magnesium stearate, magnesium lauryl stearate, sodium stearyl fumarate, stearic acid, calcium stearate, zinc stearate, potassium benzoate, sodium benzoate and talc or a mixture thereof preferably 0.5 to 3% by weight of the total weight of the pharmaceutical composition.

6. The solid oral composition as claimed in claim 1, wherein the glidant is selected from talc, colloidal silicon dioxide, magnesium stearate, and silica preferably 0.5 to 1.5% by weight of the total weight of the pharmaceutical composition.

7. The solid oral composition as claimed in claim 1, wherein the channelling is selected from mannitol, sodium chloride, sugars, polyol and glucose monohydrate and polysaccharides and mixture thereof preferably 1 to 6% by weight of the total weight of the pharmaceutical composition.

8. The solid oral composition as claimed in claim 1, wherein the solvent is selected from acetone, acetone and dichloromethane, methanol and dichloromethane, acetone and water, acetone and methanol, acetone and ethanol, dichloromethane and ethanol or ethanol and water or a mixture thereof.

9. The solid oral composition as claimed in claim 1, wherein the coating agent is present in an amount of 1 to 3% by weight of the total weight of the pharmaceutical composition.

10. A process for preparing solid oral composition of Olaparib comprising spray drying technique:
a) preparing solid dispersion of Olaparib with one or more matrix polymers by using solvent,
b) spray drying the solid dispersion of Olaparib for the removal of solvents using a spray drying equipment,
c) sifting solid dispersion of Olaparib through co-sift with fillers and glidant
d) sifting the lubricant,
e) pre-slugging the sifted material of step (c) into blender and lubricating the blend with lubricant of step (d),
f) slugging and de-slugging,
g) blending & lubricate with lubricant,
h) compressing into a tablet,
i) coating with coating agent in purified water to form a film coated tablet.
,CLAIMS:We claim:
1. A solid oral composition comprising Olaparib and hydrophilic matrix polymer in the ratio of 1: =4.

2. A solid oral composition as claimed in Claim 1 comprising
a) 10 to 50% w/w of solid dispersion of Olaparib,
b) 1 to 95% w/w of matrix polymer or a mixture thereof,
c) 0.5 to 3% w/w of lubricant or a mixture thereof,
d) 0.5 to 3% w/w of glidant,
e) 1 to 10% w/w of channelling agent
f) 1 to 3% w/w of film coating agent
g) solvent or a mixture thereof, and optionally other excipients.

3. The solid oral composition as claimed in claim 1, wherein the total amount of Olaparib in the composition is in the range of from 25mg to 250mg.

4. The solid oral composition as claimed in claim 1, wherein the hydrophilic polymers matrix is selected from Povidone K12, Povidone K90, Povidone K25, Povidone K30, Povidone 12PF, Povidone 17PF or Povidone K25 or a mixture thereof preferably 2% to 85% w/w by weight of the total weight of the pharmaceutical composition.

5. The solid oral composition as claimed in claim 1, wherein the lubricant is selected from magnesium stearate, magnesium lauryl stearate, sodium stearyl fumarate, stearic acid, calcium stearate, zinc stearate, potassium benzoate, sodium benzoate and talc or a mixture thereof preferably 0.5 to 3% by weight of the total weight of the pharmaceutical composition.

6. The solid oral composition as claimed in claim 1, wherein the glidant is selected from talc, colloidal silicon dioxide, magnesium stearate, and silica preferably 0.5 to 1.5% by weight of the total weight of the pharmaceutical composition.

7. The solid oral composition as claimed in claim 1, wherein the channelling is selected from mannitol, sodium chloride, sugars, polyol and glucose monohydrate and polysaccharides and mixture thereof preferably 1 to 6% by weight of the total weight of the pharmaceutical composition.

8. The solid oral composition as claimed in claim 1, wherein the solvent is selected from acetone, acetone and dichloromethane, methanol and dichloromethane, acetone and water, acetone and methanol, acetone and ethanol, dichloromethane and ethanol or ethanol and water or a mixture thereof.

9. The solid oral composition as claimed in claim 1, wherein the coating agent is present in an amount of 1 to 3% by weight of the total weight of the pharmaceutical composition.

10. A process for preparing solid oral composition of Olaparib comprising spray drying technique:
a) preparing solid dispersion of Olaparib with one or more matrix polymers by using solvent,
b) spray drying the solid dispersion of Olaparib for the removal of solvents using a spray drying equipment,
c) sifting solid dispersion of Olaparib through co-sift with fillers and glidant
d) sifting the lubricant,
e) pre-slugging the sifted material of step (c) into blender and lubricating the blend with lubricant of step (d),
f) slugging and de-slugging,
g) blending & lubricate with lubricant,
h) compressing into a tablet,
i) coating with coating agent in purified water to form a film coated tablet.