DESC:FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003

COMPLETE SPECIFICATION
(See section 10 and rule 13)

“SOLID DISPERSIONS OF NIRAPARIB OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF”

Glenmark Life Sciences Limited
an Indian Company, registered under the Indian Companies Act 1956, and having its registered office at Plot No. 170-172,
Chandramouli Industrial Estate,
Mohol Bazarpeth, Solapur 413213.

The following specification particularly describes the invention and the manner in which it is to be performed.
FIELD OF INVENTION
The present invention relates to a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The present invention also relates to a process for the preparation of the solid dispersion, a pharmaceutical composition comprising the solid dispersion, and its therapeutic use.
BACKGROUND OF THE INVENTION
Niraparib is known by its chemical name 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole 7-carboxamide, and is represented by a compound of formula I (the “compound I”).

I
Niraparib and its pharmaceutically acceptable salts are described in a published PCT publication no. WO2009087381A1.
Niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, is indicated for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy. In addition, it is also 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. Niraparib is marketed as Zejula® as capsules and tablets in three strengths. Zejula® contains niraparib tosylate monohydrate as the active pharmaceutical ingredient (API), which is equivalent to 100 mg, 200 mg and 300 mg niraparib base respectively.
Various polymorphic forms of niraparib tosylate are described in the literature. For instance, the PCT Publication No. WO2018183354A1 relates to Form(s) I (monohydrate), II (non-stoichiometric hydrate) and III (anhydrous) of niraparib tosylate, and processes for the preparation thereof.
PCT Publication No. WO2020072796A1 relates to crystalline niraparib free base, and compositions comprising the crystalline form of niraparib.
As per the European public assessment report (No. EMA/648982/2017) for niraparib tosylate monohydrate published by the EMA (the European Medicines Agency), niraparib is classified as BCS class II drug. According to the Biopharmaceutical Classification System (BCS), the class II drugs are characterized by poor solubility and high permeability in the human body. Poor solubility of a drug substance is one of the major problems in the preparation of oral dosage form containing such drug substance, particularly because poor the rate of solubilisation and absorption of a drug substance, lower will be its bioavailability and pharmacokinetic performance. Therefore, the right approach will be to improve the solubility properties of the drug substance in turn to improve its overall pharmacokinetic profile in order to effectively exert its therapeutic effects. The present invention attempts to provide a solution for the specified problems associated with niraparib and its pharmaceutically acceptable salts.
SUMMARY OF THE INVENTION
The present invention provides a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier as described herein.
The present invention also provides a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, and at least one surfactant.
The present invention further provides a process for the preparation of a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier; wherein the process comprises the steps of:
a) dissolving niraparib or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier in a solvent to obtain a solution or a suspension; and
b) removing the solvent from the reaction mixture obtained in the step a) to obtain the solid dispersion.
The present invention further provides a process for the preparation of a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier; wherein the process comprises the steps of:
a) dissolving niraparib or a pharmaceutically acceptable salt thereof, in a solvent to obtain a solution or a suspension;
b) adding a pharmaceutically acceptable carrier to the solution or suspension obtained in the step (a) to obtain a reaction mixture; and
c) removing the solvent from the reaction mixture obtained in the step b) to obtain the solid dispersion.
The present invention further provides a pharmaceutical composition comprising the solid dispersion of niraparib or a pharmaceutically acceptable salt thereof as described herein, and optionally one or more pharmaceutically acceptable excipients selected from a diluent, a disintegrant, a binder, a lubricant, a glidant, a surfactant or a mixture thereof.
These and other aspects of the present invention will be apparent from the following description, and reference to the accompanying drawings.
BRIEF DESCRIPTION OF DRAWINGS
Figure 1 illustrates characteristic XRPD (X-Ray Powder Diffraction) pattern of the solid dispersion of niraparib tosylate monohydrate as obtained in example 1.
Figure 2 illustrates characteristic XRPD (X-Ray Powder Diffraction) pattern of the solid dispersion of niraparib tosylate monohydrate as obtained in example 2.

DETAILED DESCRIPTION OF THE INVENTION
In one aspect, the present invention relates to a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier as described herein.
As used herein the term "solid dispersion" refers to a system in a solid state comprising at least two components, and in the context of the present invention, one of the components is niraparib or a pharmaceutically acceptable salt thereof, for example, niraparib tosylate monohydrate, which is dispersed throughout the other component, and the other component is a pharmaceutically acceptable carrier, and optionally, a surfactant.
As used herein, the term "pharmaceutically acceptable" refers to those compounds, materials, excipients, carrier, which will be considered by a prudent medical practitioner, suitable for use in the manufacture of dosage forms considered for administration to humans and animals without excessive toxicity, irritation, allergic response or other complications commensurate with a reasonable benefit/risk ratio.
As used herein, the term “pharmaceutically acceptable carrier” refers to both polymers and non-polymeric excipients, and combinations thereof, capable of dissolving or molecularly dispersing niraparib or a pharmaceutically acceptable salt thereof. In the context of the present invention, the term “non-polymeric excipients” refers to “non-polymeric porous materials”.
The pharmaceutically acceptable salts of niraparib include, but are not limited to, toluene sulfonate (tosylate), methanesulfonate (mesylate), ethanesulfonate (esylate), 2-hydroxyethanesulfonate, benzenesulfonate (besylate), acetate, propionate, butyrate, isobutyrate, valerate, maleate, hydroxymaleate, acrylate, fumarate, malate, tartrate, citrate, salicylate, succinate, lactate, phthalate, oxalate, succinate, benzoate, stearate, ascorbate, palmitate, oleate, pyruvate, malonate, laurate, glutarate, glutamate, hydrochloride, hydrobromide, nitrate, sulfate, bisulfate and phosphate. A person of skill in the art would understand that these pharmaceutically-acceptable salts of niraparib can be prepared by separately reacting the compound in its free base form with a suitable acid.
As used herein, the term “about” refers to any value which lies within the range defined by a number up to 10% of the value.
As used herein, the abbreviation w/w denotes weight by weight of the total contents.
In the context of the present invention, the term “optionally” used in reference to surfactants in one or more aspects/embodiments of the present invention means that it is not mandatory to add the surfactant to arrive at the solid dispersion of the present invention as described herein. It will be apparent to a person skilled in the art that addition of surfactant is optional, and that it does not deviate from the scope of the present invention.
In an embodiment, the niraparib or a pharmaceutically acceptable salt thereof contained in the solid dispersion of the present invention is in a crystalline form or an amorphous form.
In an embodiment, the pharmaceutically acceptable carrier is selected from a polymer or a non-polymeric porous material.
In an embodiment, the polymer is selected from homopolymers or copolymers of N-vinyl lactams, cellulose derivatives, polyalkylene oxides, polyacrylates, polymethacrylates, vinyl acetate polymers (polyvinyl acetate), polyvinyl acetate phthalate, polyacrylamides, polyvinyl alcohol, polyhydric alcohol, oligo- or polysaccharides, polyhydroxyalkylacrylates, polyhydroxyalkyl-methacrylates, copolymers of methyl methacrylate; polyethylene glycols (PEGs); or a mixture thereof.
In another embodiment, the polymer is a homopolymer or a copolymer of N-vinyl lactams selected from polyvinylpyrrolidone (PVP), polyvinylpolypyrrolidone (crospovidone), polyvinylcaprolactam (Soluplus), copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate (copovidone) or a mixture thereof. Examples of commercially available polyvinylpyrrolidone (PVP) include PVP K17, PVP K25, PVP K30, PVP K90, and the like.
In yet another embodiment, the polymer is a cellulose derivative selected from methyl cellulose, ethyl cellulose, propyl cellulose, carboxymethyl cellulose, methyl cellulose adipate, hydroxypropyl cellulose; 5-carboxypent-1-yl hydroxypropyl cellulose, methyl 5-carboxypentyl cellulose, ethyl 5-carboxypentyl cellulose, cellulose acetate propionate, cellulose acetate butyrate, carboxymethyl cellulose acetate butyrate, hydroxypropyl methyl cellulose, cellulose acetate adipate, cellulose acetate phthalate, cellulose acetate suberate, cellulose acetate adipate hydroxyethyl ester, cellulose acetate adipate propionate, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose acetate succinate, or a mixture thereof.
In another further embodiment, the polymer is polyalkylene oxides selected from polyethylene oxide (polyoxyethylene), polypropylene oxide, copolymers of poly(ethylene oxide) and poly(propylene oxide), or a mixture thereof.
In another embodiment, the polymer is a polyacrylate or polymethacrylate selected from acrylic acid/ethyl acrylate copolymers, methacrylic acid/methyl methacrylate copolymers, butyl methacrylate/2-dimethylaminoethyl methacrylate copolymers, poly (hydroxyalkyl acrylates), poly(hydroxyalkyl methacrylates, or a mixture thereof. Commercially available polymethacrylates are sold under the trade name Eudragit®. In the context of the present invention, the polymethacrylates are alternatively referred to as “Eudragit polymers”. Examples of Eudragit polymers include Eudragit L12,5; Eudragit L100; Eudragit EPO; Eudragit L 100-55; Eudragit L 30 D-55; Eudragit L 100; Eudragit S 12, 5P; Eudragit S 12,5; Eudragit S 100; Eudragit FS 30D; Eudragit RL 12,5; Eudragit RL100; Eudragit RS 100; Eudragit RS PO; Eudragit RS 30D, Eudragit E-100, and the like.
In another further embodiment, the polymer is a vinyl acetate polymer selected from copolymers of vinyl acetate and crotonic acid, partially hydrolyzed polyvinyl acetate (also known as partially saponified “polyvinyl alcohol”), or a mixture thereof.
In another embodiment, the polymer is a polyhydric alcohol selected from glycerin, propylene glycol, polyethylene glycol, and 1,3-butanediol, 1,2,4-butanetriol, 1,3,5-pentanetriol, 1,2,6-hexanetriol, or a mixture thereof.
In yet another further embodiment, the polymer is an oligo- or polysaccharides selected from carrageenans, galactomannans, xanthan gum, cyclodextrin or hyaluronic acid.
In an embodiment, the pharmaceutically acceptable carrier used in the solid dispersion of the present invention is a non-polymeric porous material.
In an embodiment, the non-polymeric porous material is selected from mesoporous silica, colloidal silica (colloidal silicon dioxide), calcium silicate, magnesium silicate aluminosilicate (zeolite), or magnesium aluminosilicate.
In an embodiment, the present invention provides a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier selected from polyvinyl pyrrolidone (PVP), polyvinylpolypyrrolidone (crospovidone), polyvinyl pyrrolidone-vinyl acetate copolymer (PVP-VA), polyethylene glycol, ethyl cellulose, methyl cellulose, cyclodextrin, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl methyl cellulose acetate succinate (HPMC-AS), hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose succinate (HPMCS), Eudragit polymer, mesoporous silica, colloidal silica, magnesium aluminosilicate, or a mixture thereof.
In another embodiment, the present invention provides a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and a polymer selected from hydroxypropylmethylcellulose (HPMC), or hydroxypropylmethylcellulose acetate succinate (HPMC-AS) or a mixture thereof.
In yet another embodiment, the present invention provides a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and a polymer selected from polyvinyl pyrrolidone (PVP), polyvinylpolypyrrolidone (crospovidone), or a mixture thereof.
In an embodiment, the present invention provides a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and Eudragit polymer as the pharmaceutically acceptable carrier.
In an embodiment, the present invention provides a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and polyvinyl alcohol as the pharmaceutically acceptable carrier.
In an embodiment, the present invention provides a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and polyvinyl pyrrolidone as the pharmaceutically acceptable carrier.
In an embodiment, as may be combined with any of the preceding paragraphs, the solid dispersion of the present invention comprising niraparib or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, further comprises a surfactant.
In an embodiment, as may be combined with any of the preceding paragraphs, the surfactant used in the solid dispersion of the present invention is selected from polysorbate 20 (Tween® 20), polysorbate 80 (Tween® 80), sorbitan monolaurate (Span 20®), sorbitan monooleate (Span 80®), sodium docusate, sodium lauryl sulfate, poloxamers or a mixture thereof.
In an embodiment, as may be combined with any of the preceding paragraphs, the ratio of niraparib or a pharmaceutically acceptable salt thereof, to the pharmaceutically acceptable carrier ranges from about 1: 0.5 to about 1:10 [w/w].
In an embodiment, as may be combined with any of the preceding paragraphs, the ratio of niraparib or a pharmaceutically acceptable salt thereof, to the pharmaceutically acceptable carrier ranges from about 1: 1 to about 1:5 [w/w].
In an aspect, the present invention also provides a process for the preparation of a solid dispersion comprising niraparib tosylate monohydrate and a pharmaceutically acceptable carrier; wherein the process comprises the steps of:
a) dissolving niraparib tosylate monohydrate and a pharmaceutically acceptable carrier in a solvent to obtain a solution or a suspension; and
b) removing the solvent from the reaction mixture obtained in the step a) to obtain the solid dispersion.
In one embodiment, the solvent used in the step a) of the above process, may be selected from the group consisting of (C1-C6)alkyl alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and the like; halogenated hydrocarbons such as methylene dichloride, ethylene dichloride, chloroform and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, tetrahydrofuran, 1-4-dioxane and the like; esters such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, butyl acetate, tert-butyl acetate and the like; ketones such as acetone, ethyl methyl ketone and the like, methyl isobutyl ketone; dimethyl sulfoxide (DMSO); hydrocarbons such as hexane, heptane, toluene, xylene and the like; N-methyl pyrrolidinone (NMP), water or a mixture thereof.
In an embodiment, the step a) involving dissolving niraparib tosylate monohydrate and a pharmaceutically acceptable carrier in a solvent is carried out at a temperature ranging from about 25°C to about 90°C.
In an embodiment, the reaction mixture obtained in the step (a) may be stirred for a suitable time. The stirring time may range from about 3 minutes to about 120 minutes, or longer.
In an embodiment, the step (a) of the above process further comprises the step of adding a surfactant to the reaction mixture containing niraparib tosylate monohydrate and a pharmaceutically acceptable carrier.
In an embodiment, in the step (a) of the above process, surfactant is dissolved in a solvent prior to addition to the solution or suspension of the step (a).
In an embodiment, the solvent used for dissolving the surfactant may be selected from the solvents as described in respect of the step (a) of the above process.
In one embodiment, in the step (b) of the above process, the solvent is removed by methods selected from the group consisting of evaporation, distillation, concentrating the reaction mixture, filtration, freeze drying and spray drying.
In an embodiment, the pharmaceutically acceptable carrier used in the step (a) of the above process is selected from a polymer or a non-polymeric porous material as described in any of the preceding embodiments related to the pharmaceutically acceptable carrier per se, the polymers, and/or a non-polymeric porous material.
In an embodiment, the surfactant used in the step (a) of the above process is selected from the surfactants described in any of the preceding embodiments.
In an aspect, the present invention also provides a process for the preparation of a solid dispersion comprising niraparib tosylate monohydrate and a pharmaceutically acceptable carrier; wherein the process comprises the steps of:
a-1) dissolving niraparib tosylate monohydrate in a solvent to obtain a solution or a suspension;
b-1) adding a pharmaceutically acceptable carrier to the solution or suspension obtained in the step (a-1) to obtain a reaction mixture; and
c-1) removing the solvent from the reaction mixture obtained in the step (b-1) to obtain the solid dispersion.
In one embodiment, the solvent used in the step (a-1) of the above process, may be selected from the group consisting of (C1-C6)alkyl alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and the like; halogenated hydrocarbons such as methylene dichloride, ethylene dichloride, chloroform and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane and the like; esters such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, butyl acetate, tert-butyl acetate and the like; ketones such as acetone, ethyl methyl ketone, methyl isobutyl ketone and the like; dimethyl sulfoxide (DMSO); hydrocarbons such as hexane, heptane, toluene, xylene and the like; N-methyl pyrrolidinone (NMP), water or a mixture thereof.
In an embodiment, the step (a-1) involving dissolving niraparib tosylate monohydrate in a solvent is carried out at a temperature ranging from about 25°C to about 90°C.
In an embodiment, the reaction mixture obtained in the step (b-1) may be stirred for a suitable time. The stirring time may range from about 3 minutes to about 120 minutes, or longer.
In an embodiment, the step (b-1) of the above process further comprises the step of adding a surfactant to the reaction mixture containing niraparib tosylate monohydrate and a pharmaceutically acceptable carrier.
In another embodiment, the step (b-1) of the above process further comprises the step of adding a surfactant, wherein the surfactant is added together with the pharmaceutically acceptable carrier to the solution or suspension obtained in the step (a-1).
In an embodiment, in the step (b-1) of the above process, the pharmaceutically acceptable carrier is dissolved in a solvent prior to addition to the solution or suspension of the step (a-1).
In an embodiment, in the step (b-1) of the above process, the pharmaceutically acceptable carrier and the surfactant are dissolved in a solvent prior to addition to the solution or suspension of the step (a-1).
In an embodiment, the solvent used for dissolving the pharmaceutically acceptable carrier and/or the surfactant may be selected from the solvents as described in respect of the step (a-1) of the above process.
In one embodiment, in the step (c-1) of the above process, the solvent is removed by methods selected from the group consisting of evaporation, distillation, concentrating the reaction mixture, filtration, freeze drying and spray drying.
In an embodiment, the pharmaceutically acceptable carrier used in the step (b-1) of the above process is selected from a polymer or a non-polymeric porous material as described in any of the preceding embodiments related to the pharmaceutically acceptable carrier per se, the polymers, and/or a non-polymeric porous material.
In an embodiment, the surfactant used in the step (b-1) of the above process is selected from the surfactants described in any of the preceding embodiments.
In an embodiment, as may be combined with one or more of the preceding paragraphs, the present invention provides a solid dispersion comprising a pharmaceutically acceptable salt of niraparib and a pharmaceutically acceptable carrier; wherein the pharmaceutically acceptable salt may be selected from the group consisting of toluene sulfonate (tosylate), benzenesulfonate (besylate), fumarate, succinate and sulfate.
In an embodiment, as may be combined with one or more of the preceding paragraphs, the pharmaceutically acceptable salt of niraparib contained in the present invention is niraparib tosylate monohydrate represented by the compound of formula II (the “compound II”).

II
In an embodiment, as may be combined with the preceding paragraphs, the present invention provides a solid dispersion comprising niraparib tosylate monohydrate, the compound II and a pharmaceutically acceptable carrier.
The solid dispersion comprising niraparib tosylate monohydrate, and a pharmaceutically acceptable carrier, with or without surfactant as described in one or more embodiments of the present invention may be an amorphous solid dispersion.
In the context of the present invention, niraparib or pharmaceutically acceptable salts thereof can be prepared by methods of preparation described in US Pat. No. 8,071,623 and PCT Publication No. WO2009087381A1.
In an embodiment, the present invention provides a solid dispersion comprising niraparib tosylate monohydrate and an Eudragit L-100 55 polymer, wherein the solid dispersion is characterised by the X-ray powder diffraction pattern substantially as shown in Figure 1.
In another embodiment, the present invention provides a solid dispersion comprising niraparib tosylate monohydrate and an Eudragit L-100 55 polymer, wherein the solid dispersion is in an amorphous form.
In an embodiment, the present invention provides a solid dispersion comprising niraparib tosylate monohydrate and Eudragit E-100, wherein the solid dispersion is characterised by the X-ray powder diffraction pattern substantially as shown in Figure 2.
In another embodiment, the present invention provides a solid dispersion comprising niraparib tosylate monohydrate and an Eudragit E-100 polymer, wherein the solid dispersion is in an amorphous form.
The solid dispersion of the present invention comprising niraparib tosylate monohydrate and a pharmaceutically acceptable carrier (as described herein), meets the standard stability criteria under a variety of accelerated stability conditions, such as elevated temperature and relative humidity.
The stability of the solid dispersion of the present invention may be determined by evaluating the change in the physical state i.e. crystalline niraparib tosylate monohydrate vis-à-vis the amorphous of niraparib tosylate monohydrate contained in the dispersion. Specifically, the fraction of niraparib tosylate monohydrate in the crystalline state in the solid dispersion may be measured by any standard physical measurement, such as X-ray powder diffraction method.
The solid dispersion of the present invention comprising niraparib tosylate monohydrate and a pharmaceutically acceptable carrier (as described herein), may be suitable for use in the preparation of pharmaceutical composition.
Accordingly, in an aspect, the present invention provides a pharmaceutical composition comprising the solid dispersion as described in any of the preceding embodiments related to the solid dispersion, and optionally one or more pharmaceutical acceptable excipients selected from a diluent, a disintegrant, a binder, a lubricant, a glidant, a surfactant or a mixture thereof.
In an embodiment, the present invention provides a pharmaceutical composition comprising the solid dispersion, wherein the solid dispersion is present in 50 to 80 % w/w.
In an embodiment, the present invention provides a pharmaceutical composition comprising the solid dispersion, wherein the solid dispersion is obtained by the processes for the preparation of the solid dispersion as described herein.
In another embodiment, the pharmaceutical composition comprising the solid dispersion is in solid oral dosage form selected from a tablet or a capsule.
The present invention further relates to use of the solid dispersion of the present invention or the pharmaceutical composition comprising the solid dispersion, in the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy and/or for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal.
Niraparib tosylate monohydrate used in the solid dispersion of the present invention has a chemical purity greater than 95% w/w as measured by High-performance liquid chromatography (HPLC).
Niraparib tosylate monohydrate used in the solid dispersion of the present invention has a chemical purity greater than 99% w/w as measured by HPLC.
In one embodiment, the present invention provides pharmaceutical composition comprising a solid dispersion of niraparib or a pharmaceutically acceptable salt thereof; obtained by the processes herein described, wherein the solid dispersion has a D50 and D90 particle size of less than about 200 microns, preferably less than about 100 microns, more preferably less than about 50 microns, still more preferably less than about 20 microns.

Examples:
General methods:
X-Ray Powder Diffraction (XRPD) (Instrumental settings):
Incident Beam Optics:
PreFIX Module : Programmable Divergence Slit and Anti-scatter Slit
(Offset 0.00°)
Filter : Nickel
Soller Slit : Soller 0.02 rad
Mask : 10mm
Divergence Slit : PDS
Automatic, 10mm Irradiated length, Offset 0.00mm
Anti-scatter Slit : Slit Fixed 1/2°
Beam Knife : Beam Knife for MPD systems
Diffracted Beam Optics:
PreFIX Module : Pixcel (Offset 0.00°)
Soller Slit : Soller 0.02 rad
Anti-scatter Slit : Programmable Anti-scatter Slit
Automatic, 10mm Observed length, Offset 0.00mm
Detector : Pixcel Scanning Mode, Active length (2T) = 2.122°
Measurement Parameters:
Scan axis : Gonio
Scan mode : Continuous
Start angle (°) : 2.0
End angle (°) : 50.0
Step size (°) : 0.0170
Time per step (s) : 50

Example 1: Preparation of a solid dispersion of niraparib tosylate monohydrate with Eudragit L-100 55
Niraparib tosylate monohydrate (5 g) and Eudragit L-100 55 (5 g) were dissolved in methanol (100 ml) at a temperature ranging from 50°C to 60°C to obtain a clear solution. The solution was stirred for about 5 min to about 10 min. The solution was then subjected to distillation under vacuum at a temperature ranging between 40°C to 50°C to obtain the solid dispersion. Yield: 8 g.
Example 2: Preparation of a solid dispersion of niraparib tosylate monohydrate with Eudragit E-100
Niraparib tosylate monohydrate (5 g) and Eudragit E-100 (5 g) were dissolved in methanol (100 ml) at a temperature ranging from 50°C to 60°C to obtain a clear solution. The solution was stirred for about 5 min to about 10 min. The solution was then subjected to distillation under vacuum at a temperature ranging between 40°C to 50°C to obtain the solid dispersion. Yield: 9 g.
Example 3: Preparation of a solid dispersion of niraparib tosylate monohydrate with polyvinyl alcohol.
Niraparib tosylate monohydrate (5 g) and polyvinyl alcohol (5 g) were dissolved in ethanol (100 ml) at a temperature ranging from 70°C to 85°C to obtain a clear solution. The solution was stirred for about 5 min to about 10 min. The solution was then subjected to distillation under vacuum at a temperature ranging between 40°C to 50°C to obtain the solid dispersion. Yield: 9 g.
Example 4: Preparation of a solid dispersion using niraparib tosylate monohydrate with polyvinyl pyrrolidone.
Niraparib tosylate monohydrate (5 g) and polyvinyl pyrrolidone (PVP K-25) (5 g) were dissolved in ethanol (100 ml) at a temperature ranging from 70°C to 85°C to obtain a clear solution. The solution was stirred for about 5 min to about 10 min. The solution was then subjected to distillation under vacuum at a temperature ranging from 40°C to 50°C to obtain the solid dispersion. Yield: 9 gm.

CLAIMS:We claim,

1. A solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier selected from a polymer or a non-polymeric porous material.

2. The solid dispersion as claimed in claim 1, wherein the pharmaceutically acceptable carrier is a polymer selected from homopolymers or copolymers of N-vinyl lactams, cellulose derivatives, polyalkylene oxides, polyacrylates, polymethacrylates (Eudragit polymers), vinyl acetate polymers, (polyvinyl acetate), polyvinyl acetate phthalate, polyacrylamides, polyvinyl alcohol, polyhydric alcohol, oligo- or polysaccharides, polyhydroxyalkylacrylates, polyhydroxyalkyl-methacrylates, copolymers of methyl methacrylate, polyethylene glycols (PEGs), or a mixture thereof.

3. The solid dispersion as claimed in claim 1 or claim 2, wherein the polymer is a homopolymer or a copolymer of N-vinyl lactams selected from polyvinylpyrrolidone (PVP), polyvinylpolypyrrolidone (crospovidone), polyvinylcaprolactam (Soluplus), copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate (copovidone) or a mixture thereof.

4. The solid dispersion as claimed in claim 1 or claim 2, wherein the polymer is a Eudragit polymer.

5. The solid dispersion as claimed in claim, 1 or claim 2, wherein the polymer is a cellulose derivative selected from methyl cellulose, ethyl cellulose, propyl cellulose, carboxymethyl cellulose, methyl cellulose adipate, hydroxypropyl cellulose, 5-carboxypent-1-yl hydroxypropyl cellulose, methyl 5-carboxypentyl cellulose, ethyl 5-carboxypentyl cellulose, cellulose acetate propionate, cellulose acetate butyrate, carboxymethyl cellulose acetate butyrate, hydroxypropyl methyl- cellulose, cellulose acetate adipate, cellulose acetate phthalate, cellulose acetate suberate, cellulose acetate adipate hydroxyethyl ester, cellulose acetate adipate propionate, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose succinate, hydroxypropyl methyl cellulose acetate succinate, or a mixture thereof.

6. The solid dispersion as claimed in claim 1 or claim 2, wherein the pharmaceutically acceptable carrier is a non-polymeric porous material selected from mesoporous silica, colloidal silica (colloidal silicon dioxide), calcium silicate, magnesium silicate, aluminosilicate (zeolite) or magnesium aluminosilicate.

7. The solid dispersion as claimed in any one of the preceding claim 1 to claim 6, wherein the ratio of niraparib or a pharmaceutically acceptable salt thereof to the pharmaceutically acceptable carrier ranges from about 1: 0.5 to about 1:10 [w/w].

8. The solid dispersion as claimed in any one of the preceding claim 1 to claim 7, wherein the solid dispersion further comprises one or more surfactants, wherein the surfactant is selected from polysorbate 20 (Tween® 20), polysorbate 80 (Tween® 80), sorbitan monolaurate (Span 20®), sorbitan monooleate (Span 80®), sodium docusate, sodium lauryl sulfate, poloxamers or a mixture thereof.

9. The solid dispersion as claimed in any one of the preceding claims 1 to 8, wherein the pharmaceutically acceptable salt of niraparib is niraparib tosylate.

10. A process for the preparation of a solid dispersion comprising niraparib or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier; wherein the process comprises the steps of:
a) dissolving niraparib or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier in a solvent to obtain a solution or a suspension; and
b) removing the solvent from the reaction mixture obtained in the step a) to obtain the solid dispersion.

11. A process for the preparation of the solid dispersion as claimed in claim 10, wherein the process further comprises a step of adding a surfactant to the reaction mixture of step a).

12. The process as claimed in claim 10, wherein in the step b), the solvent is removed by a method selected from the group consisting of evaporation, distillation, concentrating the reaction mixture, filtration, freeze drying and spray drying.