CLIAMS:We claim:
1. A pharmaceutical composition comprising lurasidone and one or more pharmaceutically acceptable excipients, wherein the particle size distribution (D90) of lurasidone is about 1 µm to 25 µm.

2. The pharmaceutical composition according to claim 1, wherein pharmaceutically acceptable excipients is selected from diluent, binder, disintegrant, sweetening agent, flavoring agent, lubricant and glidant.

4. A pharmaceutical composition comprising
a) about 1- about 40% of lurasidone,
b) about 10- about 80% diluent,
c) about 1- about 10% binder,
d) about 1- about 25% disintegrant,
e) about 0.05- about 10% lubricant and/or glidant;
wherein, lurasidone has the particle size distribution D90 about 1 µm to 25 µm.

5. A pharmaceutical composition comprising
a) about 1- about 40% of Lurasidone,
b) about 10- about 80% mannitol and/or lactose,
c) about 1- about 10% hypromellose,
d) about 1- about 25% crospovidone and/or croscarmellose sodium,
e) about 0.05- about 10% magnesium stearate and/or colloidal silicon dioxide
wherein, lurasidone has the particle size distribution D90 about 1 µm to 25 µm.

6. A pharmaceutical composition and process for the preparing pharmaceutical formulation, substantially as described and illustrated by examples herein.
,TagSPECI:The following specification particularly describes the invention and the manner in which it is to be performed.
PHARMACEUTICAL COMPOSITIONS OF LURASIDONE

Field of the Invention
The present invention relates to pharmaceutical compositions comprising lurasidone. The present invention relates to pharmaceutical compositions comprising lurasidone, and one or more pharmaceutically acceptable excipients. The present invention also relates to a process for the preparation of pharmaceutical composition of lurasidone with specific particle size distribution. In particular, the invention relates to pharmaceutical compositions comprising lurasidone having a specific particle size distribution. Such specific particle size distribution of lurasidone provides increased bioavailability, increased efficacy.

Background of the Invention
Lurasidone is an atypical antipsychotic drug used to treat schizophrenia, bipolar disorders or senile dementia. Lurasidone is chemically known as (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1ylmethyl] cyclohexylmethyl}hexa hydro -4,7-methano-2H-isoindole-1,3-dione.
U.S. Patent No. 5,532,372 discloses lurasidone and its acid addition salts and their production processes and their use as anti-psycotic agents (neuroleptic agents, anti-anxiety agents), especially for therapy of schizophrenia, senile insanity, manic-depressive psychosis, neurosis, etc.
A commercially available product containing Lurasidone Hydrochloride is marketed in USA under the brand name LATUDA® and is available in the dosages of 20 mg, 40mg, 60mg, 80mg and 120 mg lurasidone. LATUDA® is indicated for the treatment of Schizophrenia and depressive episodes associated with Bipolar I Disorder.
U.S. Patent No. 7,727,553 discloses a pharmaceutical preparation in the form of a rapidly disintegrating oral preparation comprising granules comprising lurasidone, two disintegrating agents, a water-soluble excipient and a polymer binder.
U.S. Patent No. US 8,729,085 discloses composition comprises lurasidone, a pregelatinized starch, a water-soluble excipient and water-soluble polymer binder; wherein wherein a content of lurasidone in the preparation is 20 to 45% (wt/wt), and the pregelatinized starch is incorporated in an amount of 20 to 50% (wt/wt) based on the weight of the preparation.
International publication No. WO 2012/156981 discloses pharmaceutical compositions of lurasidone and salts thereof with one or more water insoluble pharmaceutical excipients and wherein the composition is free of water soluble excipients.
One of the prior art reference emphasize on using pregelatinized starch, a water-soluble excipient and water-soluble polymer binder. While another prior art emphasize on pharmaceutical composition without using water soluble excipients and emphasize on the pharmaceutical composition comprising water insoluble pharmaceutical excipients viz. starch, ethylcellulose, microcrystalline cellulose etc.
Surprisingly, it has been found that pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients with specific particle size distribution of lurasidone provide equivalent dissolution profile.
Surprisingly, it has also been found that pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients wherein the particle size distribution of Lurasidone is playing a major role in dissolution lurasidone from the final dosage forms.

Summary of the invention
An aspect of the present application relate to pharmaceutical compositions comprising lurasidone.
An aspect of the present application relate to pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients.
An aspect of the present application relate to pharmaceutical compositions comprising lurasidone, and one or more pharmaceutically acceptable excipients selected from diluent, binder, disintegrant, sweetening agent, flavoring agent, lubricant and glidant.
An aspect of the present application relate to pharmaceutical compositions comprising lurasidone with specific particle size distribution of lurasidone.
An aspect of the present application further relates to processes for preparation of the compositions.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone, and one or more pharmaceutically acceptable excipients, wherein lurasidone has a particle size distribution of D90 about 1 µm to about 500 µm, or about 1 µm to about 100 µm; or about 1 µm to 50 µm or about 1 µm to 25 µm and D50 from about 1 µm to about 100 µm, or about 1 µm to about 50 µm or about 1 µm to about 20 µm or about 1 µm to about 10µm.
An aspect of the present application relate to pharmaceutical compositions comprising lurasidone has the particle size distribution D90 about 1 µm to 25 µm.
An aspect of the present application relate to pharmaceutical compositions comprising
a) about 1- about 40% of lurasidone,
b) about 10- about 80% diluent,
c) about 1- about 10% binder,
d) about 1- about 25% disintegrant,
e) about 0.05- about 10% lubricant and/or glidant;
wherein, lurasidone has the particle size distribution D90 about 1 µm to 25 µm.
An aspect of the present application relate to pharmaceutical compositions of lurasdone comprising, and at least one selected from mannitol, lactose, Croscarmellose sodium, Crospovidone, Hypromellose, Magnesium Stearate, wherein, lurasidone has the particle size distribution D90 about 1 µm to 25 µm.

Aspect of the present application relate to pharmaceutical compositions comprising
a) about 1- about 40% of Lurasidone,
b) about 10- about 80% mannitol and/or lactose,
c) about 1- about 10% hypromellose,
d) about 1- about 25% crospovidone and/or croscarmellose sodium,
e) about 0.05- about 10% magnesium stearate and/or colloidal silicon dioxide
wherein, lurasidone has the particle size distribution D90 about 1 µm to 25 µm.
An aspect of the present application relate to the methods of treating treatment of schizophrenia and depressive episodes associated with bipolar I disorder pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone, wherein lurasidone is present in an amount of about 1 mg to about 120 mg.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone, and one or more pharmaceutically acceptable excipients, wherein pharmaceutical compositions can be prepared in the form of tablets, granules, matrix tablets, multilayered tablets, powders, pellets, capsules, minitablets, microcapsules, multiple unit particles, and the like.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients, wherein methods of preparing said compositions include one or more of processes such as direct compression, wet granulation, dry granulation, solvent evaporation, fluid bed granulation, spray drying, and extrusion-spheronization.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone, and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical compositions can be film coated with one or more coating agents.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone, wherein the percentage of lurasidone is released not less than about 80% within about 15 minutes when subjected to an in vitro dissolution study.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone, and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical compositions are stable throughout shelf life of the compositions and provide the desired therapeutic concentration of the active agent for the intended duration.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone, and one or more pharmaceutically acceptable excipients, which are substantially free of degradation impurities during manufacturing and after commercially relevant storage periods.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone, and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical compositions are packaged in a strip or a blister or a HDPE container optionally together with a desiccant and/or oxygen absorbent.

Detailed description of the invention
Surprisingly, it has also been found that pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients wherein the particle size of Lurasidone is playing a major role in dissolution lurasidone from the final dosage forms.
An aspect of the present application relate to pharmaceutical compositions comprising lurasidone.
An aspect of the present application relate to pharmaceutical compositions comprising lurasidone with specific particle size distribution of lurasidone.
An aspect of the present application relate to pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients.
An aspect of the present application relates to pharmaceutical compositions comprising lurasidone, and one or more pharmaceutically acceptable excipients, wherein lurasidone has a particle size distribution of D90 about 1 µm to about 500 µm, or about 1 µm to about 100 µm; or about 1 µm to 50 µm or about 1 µm to 25 µm and D50 from about 1 µm to about 100 µm, or about 1 µm to about 50 µm or about 1 µm to about 20 µm or about 1 µm to about 10µm.
An aspect of the present application relate to pharmaceutical compositions comprising lurasidone has the particle size distribution D90 about 1 µm to 25 µm.
In an aspect of the present application, the term "about" refers to quantitative terms, plus or minus 15%, or in another embodiment plus or minus 10% or in another embodiment plus or minus 5%.
The term “lurasidone” as used herein includes salts, active metabolites, polymorphs, hydrates, solvates, esters, prodrugs, derivatives, isomers and enantiomers.
Lurasidone, preferably Lurasidone Hydrochloride, in the composition may be present in an amount of about 0.5-120 mg, or about 20mg, or about 40 mg or about 60 mg or about 80 mg or about 120 mg.
The term "excipient" or "pharmaceutically acceptable excipient" means a component of pharmaceutical compositions that is not an active ingredient, that are useful in preparing pharmaceutical compositions are generally safe, non-toxic, and neither biologically nor otherwise undesirable, and are acceptable for veterinary use as well as human pharmaceutical use. An "excipient" or a “pharmaceutically acceptable excipient" are such as, but not limited to diluent, binder, stabilizer, lubricant, glidant, disintegrating agent, surfactant, film coating material, plasticizer, pigment, coloring agents, flavouring agent and sweetening agent and any other materials that are commonly used in solid pharmaceutical dosage form preparations.
Excipients present in pharmaceutical compositions according to the application include diluents such as calcium sulfate, cellulose acetate, dextrates, dextrin, dextrose, fructose, kaolin, lactitol, maltitol, maltodextrin, maltose, polymethacrylates, sodium chloride, sucrose, lactose, mannitol, cellulose derivatives, and the like. Different grades of lactose include, but are not limited to, lactose monohydrate, lactose DT (direct tableting), lactose anhydrous, Flowlac™, Pharmatose™ and others. Various cellulose compounds that can be used include crystalline cellulose, powdered cellulose, and cellulose acetate. Examples of crystalline cellulose products include, but are not limited to, Ceolus™ KG801, Avicel™ PH101, PH102, PH301, PH302, and PH-F20, microcrystalline cellulose 114, silicified microcrystalline cellulose, and microcrystalline cellulose 112, Microcelac™100. Other useful diluents include, but are not limited to, carmellose, sugar alcohols such as mannitol, sorbitol, and xylitol, calcium carbonate, magnesium carbonate, sodium carbonate, sodium bicarbonate, light magnesium oxide, heavy magnesium oxide, sodium hydrogen phosphate, calcium sulfate, disodium hydrogen phosphate, basic calcium phosphate, and tribasic calcium phosphate.
Pharmaceutical compositions according to the present invention may include one or more binder, such as carboxymethylcelluloses, hydroxyethylcelluloses, dextrin, gelatin, maltodextrin, polyethylene oxides, sodium alginate, hydroxypropylcelluloses, hydroxypropyl methylcellulose, polyvinylpyrrolidones or povidone (e.g., PVP-K25, PVP-K29, PVP-K30, and PVP-K90D), powdered acacia, gelatin, guar gum, carbomers (e.g., a Carbopol™ product), methyl celluloses, and polymethacrylate..
Pharmaceutical compositions according to the present invention may include one or more disintegrant, such as carmellose calcium, carboxymethylstarch sodium, croscarmellose sodium, crospovidone, examples of commercially available crospovidone products including but not being limited to crosslinked povidone, Kollidon™ CL, Polyplasdone™ XL, XI-10, and INF-10, and low-substituted hydroxypropylcelluloses. Examples of low-substituted hydroxypropylcelluloses include, but are not limited to, low-substituted hydroxypropylcellulose LH11, LH21, LH31, LH22, LH32, LH20, LH30, LH32, and LH33.
Pharmaceutical compositions according to the present invention may include one or more lubricant and glidant, such as stearic acid, magnesium stearate, calcium stearate, sodium lauryl sulphate, hydrogenated vegetable oil, hydrogenated castor oil, sodium stearyl fumarate, talc, glyceryl behenate, glyceryl monostearate, palmitic acid, carnauba wax, calcium soaps, zinc stearate, polyoxyethylene monostearates, calcium silicate, silicon dioxide, macrogols, colloidal silicon dioxide, silica derivatives, and talc.
Coloring agents may include, but are not limited to, iron oxides, lake of sunset yellow, lake of quinoline yellow, lake of erythrosine, titanium dioxide, FD&C colorants, and the like.
In an aspect of the present application, pharmaceutical compositions are made into suitable pharmaceutical dosage forms. The different pharmaceutical dosage forms include solid oral dosage forms such as, but not limited to, tablets, capsules, and sachets.
An aspect of the present application relate to pharmaceutical compositions comprising
a) about 1- about 40% of lurasidone,
b) about 10- about 80% diluent,
c) about 1- about 10% binder,
d) about 1- about 25% disintegrant,
e) about 0.05- about 10% lubricant and/or glidant;
wherein, lurasidone has the particle size distribution D90 about 1 µm to 25 µm.
An aspect of the present application relate to pharmaceutical compositions of lurasdone comprising, and at least one selected from mannitol, lactose, Croscarmellose sodium, Crospovidone, Hypromellose, Magnesium Stearate, wherein, lurasidone has the particle size distribution D90 about 1 µm to 25 µm.
Aspect of the present application relate to pharmaceutical compositions comprising
a) about 1- about 40% of Lurasidone,
b) about 10- about 80% mannitol and/or lactose,
c) about 1- about 10% hypromellose,
d) about 1- about 25% crospovidone and/or croscarmellose sodium,
e) about 0.05- about 10% magnesium stearate and/or colloidal silicon dioxide
wherein, lurasidone has the particle size distribution D90 about 1 µm to 25 µm.
An aspect of the present application further provides a process for preparing the pharmaceutical compositions of lurasidone may be prepared by one or more processes known to the person having ordinary skill in the art of pharmaceutical technology such as direct compression, wet or dry granulation, slugging, hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion-spheronization, spray drying and solvent evaporation.
Further, for granulation, operations such as mixing granulation methods using a planetary mixer, a screw mixer, and the like, high-speed mixing granulation methods using a Henschel mixer, a Super mixer, and the like, extruding granulation methods using a cylindrical granulator, a rotary granulator, a screw extruding granulator, a pellet mill type granulator, and the like, wet high-shear granulation methods, fluidized-bed granulation methods, compression granulation methods, crushing granulation methods, and spraying granulation methods can be used.
After granulation, drying using an oven dryer, a fluidized bed dryer, and the like, crushing, and sieving can be carried out to obtain granules or fine granules for use. Moreover, a granulation solvent may be used when preparing the composition according to the present application.
Equipment suitable for processing pharmaceutical compositions include one or more of rapid mixer granulators, planetary mixers, mass mixers, ribbon mixers, fluid bed processors, mechanical sifters, blenders, roller compacters, extrusion-spheronizers, compression machines, capsule filling machines, rotating bowls or coating pans, tray dryers, fluid bed dryers, rotary cone vacuum dryers, and the like, multi-mills, fluid energy mills, ball mills, colloid mills, roller mills, hammer mills, and the like, equipped with a suitable screen wherever required.
Various solvents can be used in preparing pharmaceutical compositions of the present application including, but not limited to, water, methanol, ethanol, acidified ethanol, acetone, diacetone, polyols, polyethers, oils, esters, alkyl ketones, methylene chloride, isopropyl alcohol, butyl alcohol, methyl acetate, ethyl acetate, isopropyl acetate, castor oil, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulphoxide, N, N-dimethylformamide, tetrahydrofuran, and any mixtures thereof.
In an aspect of the present application pharmaceutical compositions are in the form of film-coated tablets. Useful coating compositions comprise pre-formulated film-coating materials such as OPADRY® products (manufactured by COLORCON), including OPADRY® Blue etc.), other hydrophilic or hydrophobic substances, and mixtures thereof. Useful components for coating include, but are not limited to, plasticizers, antiadherents, opacifiers, solvents, and optionally colorants, lubricants, pigments, antifoam agents, and polishing agents.
In an aspect, a film coating composition contains the following components: polymer, plasticizer, colorant or opacifier, and vehicle. In film coating suspensions, minor quantities of flavors, surfactants, and waxes can be included. In embodiments, polymers used in film coating are cellulose derivatives, such as cellulose ethers, or acrylic polymers and copolymers. High molecular weight polyethylene glycols, polyvinylpyrrolidones, polyvinyl alcohols, and waxy materials can also be used.
Typical cellulose ethers include hydroxyethylcelluloses, hydroxypropylcelluloses, hydroxypropyl methylcellulose, and methylcellulose. Suitable acrylic polymers include synthetic polymers with diverse functionalities. They may be further modified to enhance swelling and permeability by the incorporation of materials such as water soluble cellulose ethers in order to ensure a more complete disintegration or dissolution of the film.
Plasticizers include materials such as polyethylene glycols (PEG), propylene glycols, cetanol, triacetin, citric acid esters, phthalic acid esters, dibutyl succinate, castor oil, diacetylated monoglycerides, dibutyl sebacate, diethyl phthalate, glycerin, triethyl citrate, and the like. Suitable plasticizers for use in the coating materials can be categorized into three groups: polyols (e.g., glycerol, propylene glycol, and macrogols), organic esters (e.g., phthalate esters, dibutyl sebacetate, citrate esters, and triacetin), oils or glycerides (e.g., castor oil, acetylated monoglycerides, and fractionated coconut oil).
Pigments, opacifiers such as titanium dioxide, talc, and other additives may also be included in coating compositions. The quantities of the coating applied may vary from about 0.1-20%, or about 0.5-5%, by weight of the total weight of a core composition. In embodiments, a coating is applied either directly onto the cores or onto sub-coated cores, using conventional coating techniques such as, for instance, pan coating or fluidized bed coating methods.
Antiadherents are frequently used in film coating processes to avoid sticking effects during film formation and drying. An example of a useful antiadhesive for this purpose is talc. The antiadherent is frequently present in a film coating in amounts of about 0.5% (w/w) to 15% (w/w), based upon the total weight of the coating.
Suitable colorants/opacifiers can be selected from several groups such as organic dyes and lacquers, inorganic colors, and natural colors.
Film coating dispersions can be prepared using various vehicles, such as water, alcohols, ketones, esters, chlorinated hydrocarbons, and any mixtures thereof.
An aspect of the present application provides the methods of treating schizophrenia and bipolar disorder using pharmaceutical compositions comprising lurasidone.
The term “stable” as used herein includes both chemical and physical stability. The term ‘stable’ is defined as the ability of a drug substance or drug product to remain within the established specifications to maintain its identity, strength, quality, and purity at least until its shelf life.
The term ‘shelf life’ is the time that finished products may be stored after manufacturing, during which the defined quality of a specified proportion of the product remains acceptable under expected (or specified) conditions of distribution, storage, and display. The shelf life is established by the manufacturer of a product.
The term ‘related substances’ or ‘impurities’ mean the degradation impurities or active ingredient process related impurities of drug materials.
Lurasidone related impurities include the following:
PBI Impurity: 3-(1-piperazinyl)-1, 2-benzisothiazole
LUB impurity: (3aR, 4S, 7R, 7aS) 4, 7-Methano-1H-isoindole-1,3 (2H)-dione
LUR1 Impurity: (3aR, 7aR)-4’-benzo[d]isothiazol-3-yl) octahydrospiro[isoindole-2, 1’-piperazin]-1’-ium methane sulfonate
LUR2 Endo Impurity: (3aR, 4R, 7S, 7aS)-2-(((1R, 2R)-2-((4-benzo[d]isothiazol-3-yl)piperazin-1-yl)methyl)hexahydro-1H-4, 7-methanoisoindole-1,3(2H)-dione
LUR2 RS Impurity: (3aR, 4R, 7S, 7aS)-2-(((1R, 2R)-2-((4-benzo[d]isothiazol-3-yl)piperazin-1-yl)methyl)cyclohexal)methyl)hexahydro-1H-4, 7-methanoisoindole-1,3(2H)-dione
The descriptions of excipients are illustrative and are not intended to be exhaustive or limiting. Those skilled in the art will be aware of many other substances that are useful in the practice of the application, and the use of such substances is specifically included in this application.
The different physicochemical properties of the active agent as well as of excipients are to be considered, as these properties affect processing and formulation aspects. Various important physicochemical properties include, but are not limited to, particle sizes, density (bulk density and tapped density), compressibility index, Hausner’s ratio, angle of repose, etc. Particle sizes of active pharmaceutical ingredients can affect the solid dosage form in numerous ways. For example, content uniformity (CU) of pharmaceutical dosage units can be affected by particle sizes and size distributions.
Also, particle sizes can play an important role in the dissolution of active agent from the final dosage forms, because of their solubility. An aspect of the present applications relate to pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients wherein the lurasidone has a particle size distribution of D90 about 1 µm to about 500 µm, or about 1 µm to about 100 µm; or about 1 µm to about 50 µm or 1 µm to about 25 µm or about 10 µm to about 20 µm or about 10 µm to about 15 µm and D50 from about 1 µm to about 100 µm, or about 1 µm to about 50 µm or about 1 µm to about 20 µm or about 1 µm to about 10 µm.
The D10, D50, and D90 values are useful ways for indicating a particle size distribution. D90 is a size value where at least 90 percent of the particles have a size smaller than the stated value. Likewise D10 refers to 10 percent of the particles having a size smaller than the stated value. D50 refers to at least 50 percent of the particles having a size smaller than the stated value. Methods for determining D10, D50 and D90 include those using laser light diffraction with equipment sold by Malvern Instruments Ltd., Malvern, Worcestershire, United Kingdom.
Hence, these physicochemical properties not only affect the processes of preparing the pharmaceutical formulations but also affect the performance of the pharmaceutical products, both in vitro and in vivo.
In an aspect of the present application pharmaceutical compositions have hardness values such as 1-50 kiloponds (KP), or 1-30 KP or 1-20 KP or 1-10 KP or 1-5 KP or 1-3 KP or 1-2 KP.
In an aspect of the present application pharmaceutical compositions have friability less than 5%, or less than 2%, or less than 1%.
An aspect of the present application provides pharmaceuticals compositions have ‘loss-on-drying’ (LOD) less than about 15%, or less than about 10%, after manufacturing and during their shelf-life.
An aspect of the present application provides pharmaceutical compositions intended for oral administration to a subject in need thereof.
An aspect of the present application provides processes for the preparation of pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients, wherein methods of preparing said compositions includes one or more from direct compression, wet granulation, dry granulation, solvent evaporation, hot melt granulation, hot melt extrusion, fluid bed granulation, spray drying, extrusion-spheronization.
An aspect of the present application provides a process for preparation of pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipient; wherein the said pharmaceutical compositions are prepared by granulation process as given below:
i) Dry mixing of lurasidone and/or at least one pharmaceutically acceptable excipient;
ii) Preparation of granulating fluid, optionally containing a binder;
iii) Granulating the mixture of step i) with granulation fluid of step ii);
iv) Drying the granules; and
v) Optionally milling the dried granules followed by mixing with at least one pharmaceutical excipient and lubricant and making into a suitable dosage form.
vi) optionally coat the dosage form.
An aspect of the present application provides a process for preparing of a pharmaceutical composition comprising lurasidone and one or more pharmaceutically acceptable excipient; wherein the said pharmaceutical compositions are prepared by direct compression process as given below:
i) Dry mixing of lurasidone and one or more pharmaceutically acceptable excipient;
ii) adding lubricant to step (i) and making into a suitable dosage form.
iii) optionally coat the dosage form.
An aspect of the present application provides methods of treating patients suffering from schizophrenia and depressive episodes associated with bipolar I disorder by administering a pharmaceutical composition of lurasidone.
An aspect of the present application provides pharmaceutical compositions that are stable for shelf life of compositions.
An aspect of the present application provides pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients, wherein lurasidone are chemically stable during the preparation of the compositions and also during their shelf-life.
An aspect of the present application provides pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients, wherein the chemical stability of lurasidone, are maintained during storage at 40°C and 75% RH for 1 month, 3 months, or for 6 months.
The dosage forms can be subjected to in vitro dissolution testing, such as according to Test 711 “Dissolution” in United States Pharmacopeia 29, United States Pharmacopeial Convention, Inc., Rockville, Maryland, 2005 (“USP”), to determine the rate at which the active agents are released from the dosage forms, and content of active agents can be determined in dissolution media using techniques such as high performance liquid chromatography (HPLC).
An aspect of the present application provides pharmaceutical compositions comprising lurasidone and one or more pharmaceutically acceptable excipients, wherein the release of lurasidone is at least 80% of lurasidone is released in 15 minutes when tested in USP type II apparatus with 900 mL of McIlvaine buffer (pH 3.8) [(0.0.025 M Citric acid Solution + 0.05M Na2HPO4 solution (3:2)] as the dissolution medium at 37°C, at 50 rpm.
An aspect of the present application includes use of tamper-resistant or tamper-evident packages, and/or thermo-insulated packages, for pharmaceutical compositions comprising lurasidone. The compositions may be packaged into blisters, strips, or containers such as plastic, glass, or metal containers. The packaging materials such as containers including closures, composed of polyethylene and/or polypropylene and/or glass, and blisters or strips composed of aluminum or high-density polypropylene, or polyvinyl chloride, or polyvinyl chloride coated with polyvinylidene dichloride, generally termed PVC/PVDC. The package or packaging material optionally may contain one or more oxygen absorbents or desiccants. In embodiments, formulations of the present invention can be packaged into thermo-insulated packages wherein aluminum blisters or HDPE bottle containers containing compositions are packed into suitable thermo-insulated devices such as a thermocol or an expanded polystyrene package. In embodiments, the container containing the composition is double-walled, wherein a hollow space between the walls is filled with air that acts as an insulator. In embodiments, either one or both of the closure and base foils used to make blisters containing a formulation, contains one or more layers of a desiccant.
An aspect of the present application provides pharmaceutical compositions which are chemically stable and also exhibit appreciable physical stability during the preparation of the formulations and also during their shelf-life.
The following examples further describe certain specific aspects and embodiments of the application. These examples are provided solely for the purpose of illustration, and should not be construed as limiting the scope of the disclosure in any manner.

EXAMPLES
I – Composition

S.No. Name of the ingredient Example 1 Example 2 Example 3
mg/tab
1. Lurasidone HCl 40 40 40
2. Mannitol 100.4 111.2 109.2
3. Croscarmellose sodium 4.8 - -
4. Hypromellose 4.8 4.8 4.8
5. Purified water qs qs qs
6. Croscarmellose sodium 8 2 4
7. Magnesium stearate 2 2 2
Weight of uncoated tablets 160 160 160
Film coating
10. Opadry White 4.8 4.8 4.8
11. Purified water qs qs qs
Weight of coated tablets 164.8 164.8 164.8

II - Manufacturing Procedure
1. Lurasidone HCl, Mannitol, and optionally croscarmellose sodium were shifted.
2. Hypromellose was dissolved in water.
3. Material of step 1 was granulated with solution of step 2, and the granules were dried and shifted.
4. The shifted granules were blended with croscarmellose sodium in double cone blender.
5. Materials of step 4 was lubricated with Magnesium stearate and compressed into tablets.
6. Compressed tablets were subjected to coating.

III – Physical characteristic and release profile

The tablets of examples 1-3 were subjected for in-vitro dissolution in USP type II dissolution apparatus with 900 mL of McIlvaine buffer (pH 3.8) at 37°C and 50 rpm. The results are provided below:

Time
(In minutes) Cumulative Percent of Lurasidone Released
Example 1 Example 2 Example 3
5 55 35 50
10 74 53 63
15 80 59 69
20 82 63 72
30 86 69 77
45 88 74 81
60 89 79 89

IV – Chemical stability
The tablets of examples 1-3 were stored in stability chamber and the results of the study indicates that the composition is stable under stress conditions.