DESC:The following specification particularly describes the invention and the manner in which it is to be performed:

SOLID STATE FORMS OF OLAPARIB
INTRODUCTION
Aspects of the present application relate to crystalline forms of olaparib and the processes for preparation thereof.
The drug compound having the adopted name olaparib, has a chemical name 4-[(3-{[4-(cyclopropylcarbonyl) piperazin-1-yl] carbonyl}-4-fluorophenyl) methyl] phthalazin-1(2H) one, and is represented by structure of formula I.

I
Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated as monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.
U.S. Patent No. 7,449,464 discloses process for preparation of olaparib and its isomers, salts, or solvates thereof.
U.S. Patent No. 8,247,416 discloses crystalline Form A, solvates of olaparib and processes for preparation thereof.
U.S. Patent No. 8,183,369 discloses crystalline Form L of olaparib and process for its preparation.
U.S. Patent No. 8,475,842 discloses crystalline Form H of olaparib and process for its preparation. Further, it also discloses olaparib pharmaceutical composition in the form of a solid dispersion.
The occurrence of different polymorphs is possible for some compounds. A single compound may give rise to a variety of solid forms having distinct physical properties. This variation in solid forms may be significant and may result in differences in pharmaceutical products with respect to solubility, bioavailability, stability and other properties. Because polymorphic forms can vary in their physical properties, regulatory authorities require that efforts shall be made to identify all polymorphic forms, e.g., crystalline, solvated, etc., of new drug substances.
The existence and possible number of polymorphic forms for a given compound cannot be predicted, and there are no “standard” procedures that can be used to prepare polymorphic forms of a substance. However, new forms of a pharmaceutically useful compound may provide an opportunity to improve the performance characteristics of pharmaceutical products. For example, in some cases, different forms of the same drug can exhibit very different solubility and dissolution rates. The discovery of new polymorphic forms enlarges selection of materials with which formulation scientists can design a pharmaceutically acceptable dosage form of a drug with a targeted release profile or other desired characteristics. Therefore, there remains a need for preparing new and stable polymorphic forms of olaparib.

SUMMARY
In the first embodiment, the present application provides crystalline olaparib Form-M1 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 11.9 ? 0.2, 12.5 ? 0.2, 13.6 ? 0.2, 15.8 ? 0.2, 17.1 ? 0.2, 17.5 ? 0.2, 19.5 ? 0.2, 20.8 ? 0.2, 21.7 ? 0.2, 24.6 ? 0.2 and 26.8 ? 0.2 degrees 2theta.
In the second embodiment, the present application provides a process for the preparation of crystalline olaparib Form-M1, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising benzyl alcohol; and
b) isolating crystalline olaparib Form-M1.
In the third embodiment, the application provides crystalline olaparib Form-M2 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 12.0 ? 0.2, 13.6 ? 0.2, 17.2 ? 0.2, 21.9 ? 0.2, 23.2 ? 0.2, 27.8 ? 0.2 and 34.8 ? 0.2 degrees 2theta.
In the fourth embodiment, the present application provides a process for the preparation of crystalline olaparib Form-M2, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising isopropyl alcohol; and
b) isolating the crystalline olaparib Form-M2.

In the fifth embodiment, the application provides crystalline olaparib Form-M3 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 12.0 ? 0.2, 13.7 ? 0.2, 16.1 ? 0.2, 17.2 ? 0.2, 19.8 ? 0.2, 20.7 ? 0.2, 22.2 ? 0.2, 23.2 ? 0.2, 26.5 ? 0.2, 27.8 ? 0.2 and 30.5 ? 0.2 degrees 2theta.
In the sixth embodiment, the present application provides a process for the preparation of crystalline olaparib Form-M3, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising racemic Propylene glycol or R-Propylene glycol or S-Propylene glycol; and
b) isolating the crystalline olaparib Form-M3.
In the seventh embodiment, the application provides crystalline olaparib Form-M4 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 12.1 ? 0.2, 13.8 ? 0.2, 14.6 ? 0.2, 16.1 ? 0.2, 17.3 ? 0.2, 22.3 ? 0.2 and 22.9 ? 0.2 degrees 2theta.
In the eighth embodiment, the present application provides a process for the preparation of crystalline olaparib Form-M4, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising methanol; and
b) isolating the crystalline olaparib Form-M4.
In the ninth embodiment, the present application provides a process for the preparation of crystalline olaparib ethanol solvate, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising ethanol; and
b) isolating the crystalline olaparib ethanol solvate.

BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is powder X-ray diffraction ("PXRD") pattern of crystalline olaparib Form-M1prepared according to Example 1.
Figure 2 is powder X-ray diffraction ("PXRD") pattern of crystalline olaparib Form-M2 prepared according to Example 2.
Figure 3 is powder X-ray diffraction ("PXRD") pattern of crystalline olaparib Form-M3 prepared according to Example 3.
Figure 4 is powder X-ray diffraction ("PXRD") pattern of crystalline olaparib Form-M4 prepared according to Example 6.

DETAILED DESCRIPTION
In the first embodiment, the present application provides crystalline olaparib Form-M1 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 11.9 ? 0.2, 12.5 ? 0.2, 13.6 ? 0.2, 15.8 ? 0.2, 17.1 ? 0.2, 17.5 ? 0.2, 19.5 ? 0.2, 20.8 ? 0.2, 21.7 ? 0.2, 24.6 ? 0.2 and 26.8 ? 0.2 degrees 2theta.
In the second embodiment, the present application provides a process for the preparation of crystalline olaparib Form-M1, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising benzyl alcohol; and
b) isolating crystalline olaparib Form-M1.

Providing a solution or suspension in step a) includes:
i) direct use of a reaction mixture containing olaparib that is obtained in the course of its synthesis; or
ii) dissolving or olaparib in in a solvent comprising benzyl alcohol; or
iii) providing a suspension by adding benzyl alcohol to the olaparib.

Any physical form of olaparib may be utilized for providing the solution or suspension of olaparib in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the benzyl alcohol, or less than about 150°C, less than about 130°C, less than about 100°C, less than about 70°C, less than about 40°C, less than about 20°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of olaparib is obtained without affecting its quality.
Step b) involves isolating crystalline olaparib Form-M1 from the solution obtained in step a). Isolation of crystalline Form-M1 of olaparib in step b) may involve methods including cooling, concentrating the mass, adding an anti-solvent, adding seed crystals to induce crystallization, or the like. Stirring or other alternate methods such as shaking, agitation, or the like, may also be employed for the isolation.
Optionally, isolation may be effected by combining a suitable anti-solvent with the solution obtained in step a). Anti-solvent as used herein refers to a liquid in which olaparib is less soluble or poorly soluble. An anti-solvent has no adverse effect on the quality of olaparib and it can assist in the solidification or precipitation of the dissolved starting material. Suitable anti-solvents that may be used include, but are not limited to: saturated or unsaturated, linear or branched, cyclic or acyclic, C1 to C10 hydrocarbons, such as hexanes, heptane, cyclohexane, or methylcyclohexane; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, or dimethoxyethane; or any mixtures thereof.
Suitable temperatures for isolation may be less than about 100°C, less than about 80°C, less than about 60°C, less than about 40°C, less than about 20°C, less than about 10°C, less than about 5°C, less than about 0°C, less than about -10°C, less than about -20°C, or any other suitable temperatures.
The isolated crystalline olaparib Form-M1 may be recovered by methods including decantation, centrifugation, gravity filtration, suction filtration, or any other technique for the recovery of solids under pressure or under reduced pressure. The recovered solid may optionally be dried. Drying may be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying may be carried out at temperatures less than about 100°C, less than about 80°C, less than about 60°C, less than about 50°C, less than about 30°C, or any other suitable temperatures, at atmospheric pressure or under a reduced pressure, as long as the olaparib is not degraded in quality. The drying may be carried out for any desired times until the required product quality is achieved. The dried product may optionally be subjected to a size reduction procedure to produce desired particle sizes. Milling or micronization may be performed before drying, or after the completion of drying of the product. Techniques that may be used for particle size reduction include, without limitation, ball, roller and hammer milling, and jet milling.
The resulting crystalline olaparib Form-M1 is stable upon storage at ambient temperature. For example, it does not change its description and PXRD pattern when stored by packing in a closed vial under ambient conditions for about three weeks time.
In the third embodiment, the application provides crystalline olaparib Form-M2 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 12.0 ? 0.2, 13.6 ? 0.2, 17.2 ? 0.2, 21.9 ? 0.2, 23.2 ? 0.2, 27.8 ? 0.2 and 34.8 ? 0.2 degrees 2theta.
In the fourth embodiment, the present application provides a process for the preparation of crystalline olaparib Form-M2, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising isopropyl alcohol; and
b) isolating the crystalline olaparib Form-M2.
Providing a solution or suspension in step a) includes:
i) direct use of a reaction mixture containing olaparib that is obtained in the course of its synthesis; or
ii) dissolving or olaparib in in a solvent comprising isopropyl alcohol; or
iii) providing a suspension by adding isopropyl alcohol to the olaparib.
Any physical form of olaparib may be utilized for providing the solution or suspension of olaparib in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the isopropyl alcohol, or less than about 80°C, less than about 60°C, less than about 50°C, less than about 40°C, less than about 30°C, less than about 20°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of olaparib is obtained without affecting its quality.
Step b) involves isolating crystalline olaparib Form-M2 from the solution obtained in step a). Isolation of crystalline Form-M2 of olaparib in step b) may involve methods including cooling, concentrating the mass, adding an anti-solvent, adding seed crystals to induce crystallization, or the like. Stirring or other alternate methods such as shaking, agitation, or the like, may also be employed for the isolation.
Optionally, isolation may be effected by combining a suitable anti-solvent with the solution obtained in step a). Anti-solvent as used herein refers to a liquid in which olaparib is less soluble or poorly soluble. An anti-solvent has no adverse effect on the quality of olaparib and it can assist in the solidification or precipitation of the dissolved starting material. Suitable anti-solvents that may be used include, but are not limited to: saturated or unsaturated, linear or branched, cyclic or acyclic, C1 to C10 hydrocarbons, such as hexanes, heptane, cyclohexane, or methylcyclohexane; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, or dimethoxyethane; or any mixtures thereof.
Suitable temperatures for isolation may be less than about 80°C, less than about 60°C, less than about 40°C, less than about 20°C, less than about 10°C, less than about 5°C, less than about 0°C, less than about -10°C, less than about -20°C, or any other suitable temperatures.
The isolated crystalline olaparib Form-M2 may be recovered by methods including decantation, centrifugation, gravity filtration, suction filtration, or any other technique for the recovery of solids under pressure or under reduced pressure. The recovered solid may optionally be dried. Drying may be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying may be carried out at temperatures less than about 100°C, less than about 80°C, less than about 60°C, less than about 50°C, less than about 30°C, or any other suitable temperatures, at atmospheric pressure or under a reduced pressure, as long as the olaparib is not degraded in quality. The drying may be carried out for any desired times until the required product quality is achieved. The dried product may optionally be subjected to a size reduction procedure to produce desired particle sizes. Milling or micronization may be performed before drying, or after the completion of drying of the product. Techniques that may be used for particle size reduction include, without limitation, ball, roller and hammer milling, and jet milling.
The resulting crystalline olaparib Form-M2 is stable up on storage at ambient temperature. For example, it does not change its description and PXRD pattern when stored by packing in a closed vial under ambient conditions for about four weeks-time.
In the fifth embodiment, the application provides crystalline olaparib Form-M3 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 12.0 ? 0.2, 13.7 ? 0.2, 16.1 ? 0.2, 17.2 ? 0.2, 19.8 ? 0.2, 20.7 ? 0.2, 22.2 ? 0.2, 23.2 ? 0.2, 26.5 ? 0.2, 27.8 ? 0.2 and 30.5 ? 0.2 degrees 2theta.
In the sixth embodiment, the present application provides a process for the preparation of crystalline olaparib Form-M3, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising racemic Propylene glycol or R-Propylene glycol or S-Propylene glycol; and
b) isolating the crystalline olaparib Form-M3.
Providing a solution or suspension in step a) includes:
i) direct use of a reaction mixture containing olaparib that is obtained in the course of its synthesis; or
ii) dissolving or olaparib in in a solvent comprising racemic Propylene glycol or R-Propylene glycol or S-Propylene glycol; or
iii) providing a suspension by adding racemic Propylene glycol or R-Propylene glycol or S-Propylene glycol to the olaparib.

Any physical form of olaparib may be utilized for providing the solution or suspension of olaparib in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the racemic Propylene glycol or R-Propylene glycol or S-Propylene glycol, or less than about 80°C, less than about 60°C, less than about 50°C, less than about 40°C, less than about 30°C, less than about 20°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of olaparib is obtained without affecting its quality.
Step b) involves isolating crystalline olaparib Form-M3 from the solution obtained in step a). Isolation of crystalline Form-M3 of olaparib in step b) may involve methods including cooling, concentrating the mass, adding an anti-solvent, adding seed crystals to induce crystallization, or the like. Stirring or other alternate methods such as shaking, agitation, or the like, may also be employed for the isolation.
Optionally, isolation may be effected by combining a suitable anti-solvent with the solution obtained in step a). Anti-solvent as used herein refers to a liquid in which olaparib is less soluble or poorly soluble. An anti-solvent has no adverse effect on the quality of olaparib and it can assist in the solidification or precipitation of the dissolved starting material. Suitable anti-solvents that may be used include, but are not limited to: saturated or unsaturated, linear or branched, cyclic or acyclic, C1 to C10 hydrocarbons, such as hexanes, heptane, cyclohexane, or methylcyclohexane; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, or dimethoxyethane; or any mixtures thereof.
Suitable temperatures for isolation may be less than about 100°C, less than about 80°C, less than about 60°C, less than about 40°C, less than about 20°C, less than about 10°C, less than about 5°C, less than about 0°C, less than about -10°C, less than about -20°C, or any other suitable temperatures.
The isolated crystalline olaparib Form-M3 may be recovered by methods including decantation, centrifugation, gravity filtration, suction filtration, or any other technique for the recovery of solids under pressure or under reduced pressure. The recovered solid may optionally be dried. Drying may be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying may be carried out at temperatures less than about 100°C, less than about 80°C, less than about 60°C, less than about 50°C, less than about 30°C, or any other suitable temperatures, at atmospheric pressure or under a reduced pressure, as long as the olaparib is not degraded in quality. The drying may be carried out for any desired times until the required product quality is achieved. The dried product may optionally be subjected to a size reduction procedure to produce desired particle sizes. Milling or micronization may be performed before drying, or after the completion of drying of the product. Techniques that may be used for particle size reduction include, without limitation, ball, roller and hammer milling, and jet milling.
The resulting crystalline olaparib Form-M3 is stable up on storage at ambient temperature. For example, it does not change its description and PXRD pattern when stored by packing in a closed vial under ambient conditions for about three weeks-time.
In the seventh embodiment, the application provides crystalline olaparib Form-M4 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 12.1 ? 0.2, 13.8 ? 0.2, 14.6 ? 0.2, 16.1 ? 0.2, 17.3 ? 0.2, 22.3 ? 0.2 and 22.9 ? 0.2 degrees 2theta.
In the eighth embodiment, the present application provides a process for the preparation of crystalline olaparib Form-M4, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising methanol; and
b) isolating the crystalline olaparib Form-M4.
Providing a solution or suspension in step a) includes:
i) direct use of a reaction mixture containing olaparib that is obtained in the course of its synthesis; or
ii) dissolving or olaparib in in a solvent comprising methanol; or
iii) providing a suspension by adding methanol to the olaparib.
Any physical form of olaparib may be utilized for providing the solution or suspension of olaparib in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the methanol, or less than about 60°C, less than about 50°C, less than about 40°C, less than about 30°C, less than about 20°C, less than about 10°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of olaparib is obtained without affecting its quality.
Step b) involves isolating crystalline olaparib Form-M4 from the solution obtained in step a). Isolation of crystalline Form-M4 of olaparib in step b) may involve methods including cooling, concentrating the mass, adding an anti-solvent, adding seed crystals to induce crystallization, or the like. Stirring or other alternate methods such as shaking, agitation, or the like, may also be employed for the isolation.
Optionally, isolation may be effected by combining a suitable anti-solvent with the solution obtained in step a). Anti-solvent as used herein refers to a liquid in which olaparib is less soluble or poorly soluble. An anti-solvent has no adverse effect on the quality of olaparib and it can assist in the solidification or precipitation of the dissolved starting material. Suitable anti-solvents that may be used include, but are not limited to: saturated or unsaturated, linear or branched, cyclic or acyclic, C1 to C10 hydrocarbons, such as hexanes, heptane, cyclohexane, or methylcyclohexane; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, or dimethoxyethane; or any mixtures thereof.
Suitable temperatures for isolation may be less than about 60°C, less than about 40°C, less than about 20°C, less than about 10°C, less than about 5°C, less than about 0°C, less than about -10°C, less than about -20°C, or any other suitable temperatures.
The isolated crystalline olaparib Form-M4 may be recovered by methods including decantation, centrifugation, gravity filtration, suction filtration, or any other technique for the recovery of solids under pressure or under reduced pressure. The recovered solid may optionally be dried. Drying may be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying may be carried out at temperatures less than about 100°C, less than about 80°C, less than about 60°C, less than about 50°C, less than about 30°C, or any other suitable temperatures, at atmospheric pressure or under a reduced pressure, as long as the olaparib is not degraded in quality. The drying may be carried out for any desired times until the required product quality is achieved. The dried product may optionally be subjected to a size reduction procedure to produce desired particle sizes. Milling or micronization may be performed before drying, or after the completion of drying of the product. Techniques that may be used for particle size reduction include, without limitation, ball, roller and hammer milling, and jet milling.
In the ninth embodiment, the present application provides a process for the preparation of crystalline olaparib ethanol solvate, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising ethanol; and
b) isolating the crystalline olaparib ethanol solvate.
Providing a solution or suspension in step a) includes:
i) direct use of a reaction mixture containing olaparib that is obtained in the course of its synthesis; or
ii) dissolving or olaparib in in a solvent comprising ethanol; or
iii) providing a suspension by adding ethanol to the olaparib.
Any physical form of olaparib may be utilized for providing the solution or suspension of olaparib in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the methanol, or less than about 60°C, less than about 50°C, less than about 40°C, less than about 30°C, less than about 20°C, less than about 10°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of olaparib is obtained without affecting its quality.
Step b) involves isolating crystalline olaparib ethanol solvate from the solution obtained in step a). Isolation of olaparib ethanol solvate in step b) may involve methods including cooling, concentrating the mass, adding an anti-solvent, adding seed crystals to induce crystallization, or the like. Stirring or other alternate methods such as shaking, agitation, or the like, may also be employed for the isolation.
Optionally, isolation may be effected by combining a suitable anti-solvent with the solution obtained in step a). Anti-solvent as used herein refers to a liquid in which olaparib is less soluble or poorly soluble. An anti-solvent has no adverse effect on the quality of olaparib and it can assist in the solidification or precipitation of the dissolved starting material. Suitable anti-solvents that may be used include, but are not limited to: saturated or unsaturated, linear or branched, cyclic or acyclic, C1 to C10 hydrocarbons, such as hexanes, heptane, cyclohexane, or methylcyclohexane; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, or dimethoxyethane; or any mixtures thereof.
Suitable temperatures for isolation may be less than about 60°C, less than about 40°C, less than about 20°C, less than about 10°C, less than about 5°C, less than about 0°C, less than about -10°C, less than about -20°C, or any other suitable temperatures.
The isolated olaparib ethanol solvate may be recovered by methods including decantation, centrifugation, gravity filtration, suction filtration, or any other technique for the recovery of solids under pressure or under reduced pressure. The recovered solid may optionally be dried. Drying may be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying may be carried out at temperatures less than about 100°C, less than about 80°C, less than about 60°C, less than about 50°C, less than about 30°C, or any other suitable temperatures, at atmospheric pressure or under a reduced pressure, as long as the olaparib is not degraded in quality. The drying may be carried out for any desired times until the required product quality is achieved. The dried product may optionally be subjected to a size reduction procedure to produce desired particle sizes. Milling or micronization may be performed before drying, or after the completion of drying of the product. Techniques that may be used for particle size reduction include, without limitation, ball, roller and hammer milling, and jet milling.
The resulting olaparib ethanol solvate is stable up on storage at ambient temperature and at accelerated conditions (40 °C + 2°C). For example, it does not change its description and PXRD pattern when stored by packing in a closed vial under ambient conditions for about 3 months and at accelerated conditions (40 °C + 2°C, 75% RH + 5%RH) for about 3 months.
DEFINITIONS
The following definitions are used in connection with the present application unless the context indicates otherwise. In general, the number of carbon atoms present in a given group or compound is designated “Cx-Cy”, where x and y are the lower and upper limits, respectively. For example, a group designated as “C1-C6” contains from 1 to 6 carbon atoms. The carbon number as used in the definitions herein refers to carbon backbone and carbon branching, but does not include carbon atoms of the substituents, such as alkoxy substitutions or the like.
The word “Stable” as used herein in the relation to crystalline form refers to the crystalline form that is stable up on storage. For example, it does not change its description and PXRD pattern when stored by packing in a white polyethene bag under ambient conditions for about a weeks-time.
An “aliphatic hydrocarbon” is a liquid hydrocarbon compound, which may be linear, branched, or cyclic and may be saturated or have as many as two double bonds. A liquid hydrocarbon compound that contains a six-carbon group having three double bonds in a ring is called “aromatic.” Examples of “C5-C8 aliphatic or aromatic hydrocarbons” include n-pentane, isopentane, neopentane, n-hexane, isohexane, 3-methylpentane, 2,3-dimethylbutane, neohexane, n-heptane, isoheptane, 3-methylhexane, neoheptane, 2,3-dimethylpentane, 2,4-dimethylpentane, 3,3-dimethylpentane, 3-ethylpentane, 2,2,3-trimethylbutane, n-octane, isooctane, 3-methylheptane, neooctane, cyclohexane, methylcyclohexane, cycloheptane, petroleum ethers, benzene toluene, ethylbenzene, m-xylene, o-xylene, p-xylene, trimethylbenzene, chlorobenzene, fluorobenzene, trifluorotoluene, anisole, and the like.
Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner. Reasonable variations of the described procedures are intended to be within the scope of the present application. While particular aspects of the present application have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this application.

EXAMPLES
EXAMPLE 1: Preparation of crystalline olaparib Form-M1. Olaparib -amorphous form (2 g) and benzyl alcohol (5 mL) were charged into a glass vial at 25 °C and heated to 75 °C. Filtered the solution at 26 °C and methyl tert-butyl ether (40 mL) was dumped into filtrate. The resultant mass was heated to 56 °C and the separated solid was filtered at 40 °C. Wet compound was dried in VTD at 60 °C for 2 hours to afford the title compound.
EXAMPLE 2: Preparation of crystalline olaparib Form-M2. Olaparib amorphous form (1 g) and Isopropyl alcohol (10 mL) were charged into a glass vial and the resulting suspension was stirred at 27 °C for 18 hours. Separated solid was filtered and dried at 40 °C for about 1hour in VTD to afford title compound.
EXAMPLE 3: Preparation of crystalline olaparib Form-M3. Olaparib amorphous form (1 g) and R-propylene glycol (6 mL) were charged into a glass vial and the resulting suspension was stirred at 27 °C for 18 hours. Separated solid was filtered and dried at 40 °C in VTD to afford title compound.

EXAMPLE 4: Preparation of crystalline olaparib Form-M3. Olaparib amorphous form (1 g) and S-propylene glycol (6 mL) were charged into a glass vial and the resulting suspension was stirred at 27 °C for 18 hours and the Separated solid was filtered to afford title compound.
EXAMPLE 5: Preparation of crystalline olaparib Form-M3. Olaparib amorphous form (1 g) and propylene glycol (6 mL) were charged into a glass vial and the resulting suspension was stirred at 27 °C for 18 hours and the Separated solid was filtered to afford title compound.
EXAMPLE 6: Preparation of crystalline olaparib Form-M4. Olaparib amorphous form (0.8 g) and methanol (10 mL) were charged into a glass vial and the resulting suspension was stirred at 27 °C for 2 hours. Separated solid was filtered and dried at 45 °C in VTD to afford title compound.
EXAMPLE 7: Preparation of crystalline olaparib ethanol solvate. Olaparib amorphous form (0.8 g) and ethanol (10 mL) were charged into a glass vial and the resulting suspension was stirred at 27 °C for 15 hours. Separated solid was filtered and dried at 40 °C in VTD to afford title compound.
,CLAIMS:WE CLAIM:

1. Crystalline olaparib Form-M1 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 11.9 ? 0.2, 12.5 ? 0.2, 13.6 ? 0.2, 15.8 ? 0.2, 17.1 ? 0.2, 17.5 ? 0.2, 19.5 ? 0.2, 20.8 ? 0.2, 21.7 ? 0.2, 24.6 ? 0.2 and 26.8 ? 0.2 degrees 2theta.

2. The process for preparation of crystalline olaparib Form-M1 according to claim 1, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising benzyl alcohol; and
b) isolating crystalline olaparib Form-M1.

3. Crystalline olaparib Form-M2 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 12.0 ? 0.2, 13.6 ? 0.2, 17.2 ? 0.2, 21.9 ? 0.2, 23.2 ? 0.2, 27.8 ? 0.2 and 34.8 ? 0.2 degrees 2theta.

4. The process for the preparation of crystalline olaparib Form-M2 according to claim 4, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising isopropyl alcohol; and
b) isolating the crystalline olaparib Form-M2.

5. Crystalline olaparib Form-M3 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 12.0 ? 0.2, 13.7 ? 0.2, 16.1 ? 0.2, 17.2 ? 0.2, 19.8 ? 0.2, 20.7 ? 0.2, 22.2 ? 0.2, 23.2 ? 0.2, 26.5 ? 0.2, 27.8 ? 0.2 and 30.5 ? 0.2 degrees 2theta.
6. The process for the preparation of crystalline olaparib Form-M3 according to claim 5, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising racemic Propylene glycol or R-Propylene glycol or S-Propylene glycol; and
b) isolating the crystalline olaparib Form-M3.
7. Crystalline olaparib Form-M4 characterized by its powder X-ray diffraction (PXRD) pattern having peaks at about 12.1 ? 0.2, 13.8 ? 0.2, 14.6 ? 0.2, 16.1 ? 0.2, 17.3 ? 0.2, 22.3 ? 0.2 and 22.9 ? 0.2 degrees 2theta.

8. A process for the preparation of crystalline olaparib Form-M4, according to claim 7, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising methanol; and
b) isolating the crystalline olaparib Form-M4.

9. A process for the preparation of crystalline olaparib ethanol solvate, comprising:
a) providing a solution or suspension of olaparib in a solvent comprising ethanol; and
b) isolating the crystalline olaparib ethanol solvate.