WO2018015915A1 - A parenteral controlled release composition of an atypical antipsychotic agent - Google Patents

Abstract

The present invention relates to a parenteral controlled release composition comprising one or more atypical antipsychotic or their pharmaceutically acceptable salts, one or more rate controlling polymer, optionally one or more pharmaceutically acceptable excipients. The present invention also relates to the process of preparing such compositions. Furthermore, the present invention relates to the use of said composition for the prophylaxis or treatment of psychotic disorders.

Description

A PARENTERAL CONTROLLED RELEASE COMPOSITION OF AN ATYPICAL ANTIPSYCHOTIC AGENT

FIELD OF THE INVENTION:

The present invention provides a parenteral controlled release composition comprising an atypical antipsychotic agent for the management of prophylaxis, amelioration and/or treatment of psychiatric conditions or disorders. More particularly, the invention relates to a parenteral controlled release composition comprising one or more atypical antipsychotics or there pharmaceutically acceptable salts, one or more rate controlling polymers, and one or more pharmaceutically acceptable excipients.

BACKGROUND OF THE INVENTION:

Psychotic disorders are a group of serious mental illnesses with an average age of onset in late adolescence or early adulthood. The most common psychotic disorders include schizophrenia, bipolar disorder, and major depression with psychotic features. Psychosis is characterized by disorders in basic perceptual, cognitive, affective and judgmental processes. Individuals experiencing a psychotic episode may experience hallucinations (often auditory or visual hallucinations), hold paranoid or delusional beliefs, experience personality changes and exhibit disorganized thinking (thought disorder). The thought disorder is accompanied by features such as a lack of insight into the unusual or bizarre nature of their behavior, difficulties with social interaction and impairments in carrying out the activities of daily living.

Schizophrenia is a common and serious mental disorder characterized by loss of contact with reality (psychosis), hallucinations (false perceptions), delusions (false beliefs), abnormal thinking, flattened affect, diminished motivation, and disturbed work and social functioning. Atypical antipsychotics offer several clinical benefits over the conventional antipsychotics, which were the mainstays of care until the past decade. The principal mechanism, underlying the many clinical benefits of the atypical agents is separating the antipsychotic effect from the extrapyramidal side effects (EPS). The distinct advantages over traditional antipsychotic medications include greater improvement in negative symptoms, such as social withdrawal, and lower risk of Parkinsonian side effects and tardive dyskinesia. The conventional antipsychotics are antagonists of dopamine (D2) receptors. The atypical antipsychotics likewise have D2 antagonistic properties, but possess different binding kinetics to these receptors and activity at other receptors, particularly 5-HT2A, 5-HT2c and 5-HTm (Schmidt B et al. Soc. Neurosci. Abstr., 24:2177; (1998)).

Lurasidone is an atypical antipsychotic belonging to the chemical class of Benzo(iso)thiazolepiperazine derivatives. Its chemical name is (3aR,4S,7R,7aS)-2-{(lR,2R)- 2-[4-(l,2-benzisothiazol-3-yl)piperazin-lyl-methyl]cyclohexylmethyl}hexahydro-4,7- methano-2H-isoindole-l,3-dione hydrochloride.

Lurasidone, like other recent second-generation antipsychotics (Aripiprazole, Asenapine, and Ziprasidone), is distinguished by its good metabolic tolerability profile. Lurasidone is also associated with good cardiovascular tolerability, without hypertension or widening of QT interval, whatever the dosage form used. U.S. Patent No. 5,532,372 describes 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. Lurasidone is commercially available as tablet containing 20 mg, 40 mg, 60 mg, 80 mg, or 120 mg of lurasidone hydrochloride.

As in the case of mucosal and transdermal drug delivery, where systemic bioavailability of a drug is always limited by its permeability across a permeation barrier (epithelial membrane or stratum corneum) and oral drug delivery in which the systemic bioavailability of a drug is often subjected to variable gastrointestinal transit time and biotransformation in the liver by "first pass metabolism.

Therefore, the parenteral route of administration is the most common and efficient for delivery of active drug substances with poor bio-availability and the drugs with a narrow therapeutic index. But parenteral route offers rapid onset of action with rapid declines of systemic drug level. For the sake of effective treatment it is often desirable to maintain systemic drug levels within the therapeutically effective concentration range for as long as treatment calls for. It requires frequent injection, which ultimately leads to patient discomfort. For this reason, drug delivery system which can reduce total number of injection throughout the effective treatment, improve patient compliance as well as pharmacoeconomic.

To achieve a constant drug level in the systemic circulation, two strategies can be employed: 1) to control the rate of absorption of a drug or 2) to control the rate of excretion of a drug. Controlling the absorption rate of a drug (by modifying dosage forms) is easier than controlling the excretion rate (by modifying physiology of body) of a drug.

One of the formulation technologies used to modify the release profile in parenteral dosage form is in-situ gelling technology. The development of in-situ gel systems has received considerable attention over the past few years. In- situ gel forming drug delivery systems are in principle, capable of releasing drug in a sustained manner maintaining relatively constant plasma profiles. These hydro gels are liquid at room temperature but undergo gelation when come in contact with body fluids or change in pH. Such in-situ gelling compositions have several advantages: they can be readily and reliably manufactured by standard methods; they can be stored in the form of easily-injected liquids; they can be placed locally to achieve local delivery; and they can flow prior to gelling so as to fill voids and create a less-visible subcutaneous implant.

Moreover, treatment of psychotic disorders requires daily chronic treatment and daily intake of oral formulation is inconvenient for patient. Long Acting Injectable (LAIs) have a number of advantages over oral antipsychotics. First, they should decrease noncompliance due to forgetfulness and loss of insight (e.g., due to psychotic relapse or substance abuse) because patients are followed up if they miss an appointment for their injection. Moreover, LAIs should maximize pharmacokinetic coverage and minimize antipsychotic withdrawal symptoms resulting from partial compliance. In addition, LAIs are not influenced by first- pass metabolism and decreasing the potential for drug-drug interactions.

Studies on the strategies for switching patients from oral to depot treatment suggest that this procedure can be reasonably safely performed. Some authors suggest a wash-out period between the discontinuation of the oral treatment and starting the depot therapy to avoid the risk of precipitating acute EPS. However, in clinical practice depot antipsychotic therapy is usually begun during the administration of oral treatment, followed by gradual tapering of the oral dose.

U.S. Patent No. 8,283,352 discloses a solution-type preparation comprising lurasidone as an active ingredient and containing at least one substance selected from benzyl alcohol, Ν,Ν-dimethylacetamide, lactic acid and propylene glycol. U.S. 20120091022 discloses an injectable suspension formulation comprising specific mean particle size of lurasidone along with specific nonionic surfactant to achieve sustain release formulation of lurasidone.

U.S. 20040138237 describes a depot formulation for intramuscular injection comprising ziprasidone mesylate in an amount sufficient to provide at least about 10 mgA to about 30 mgA per day of ziprasidone for at least about 8 hours to about 2 weeks, said ziprasidone mesylate solubilized with SBECD, said SBECD present at a concentration of about 5% to about 35% w/v; sodium carboxymethyl cellulose present in a concentration of about 0.25% w/v to about 2% w/v; optionally a pharmaceutically acceptable surfactant present in an amount of up to about 1%; and water.

U.S. 20140050799 describes a long-acting sustained release microsphere composition of risperidone along with a polymer blend of two uncapped lactide-glycolide copolymers and method for preparing.

Although these microspheres or microcapsules being small particles can be injected into the body with a syringe, but they do not always satisfy the demand for a uniform in-situ depot gel or a biodegradable implant. Because they are particles, that do not form a continuous film or solid implant with the structural integrity upon injection into the body. When these small particles, i.e., microspheres, or microcapsules come in contact with the body fluids, they are poorly retained because of their small size and discontinuous nature. In addition, microspheres or microcapsules prepared from biodegradable polymers containing drugs for release into the body are sometimes difficult or are expensive to produce on a large scale and their storage and injectability characteristics present compliance problems.

WO 2009060473 describes a single-component or a multi-component injectable depot gel or implant compositions comprising at least one active agent which provides a prolonged release of the active agent(s) for extended periods of time.

Currently, lurasidone is available as a tablet dosage form in market. Moreover, treatment of psychotic disorders requires chronic treatment and it is difficult for such patients to follow the daily chronic regimen of such therapy. Hence, there is a long felt need to develop alternate atypical antipsychotic formulations that provides a prolonged release of the active agent(s) for extended periods of time as well as an improved syringeability over the earlier atypical antipsychotic formulations for the treatment of psychotic disorders. SUMMARY OF THE INVENTION;

In one general aspect, the present invention provides a parenteral controlled release composition comprising one or more atypical antipsychotic or their pharmaceutically acceptable salts, one or more rate controlling polymers, wherein the composition provides a prolonged release of the active agent(s) for extended periods of time.

In yet another aspect, the present invention provides a parenteral controlled release composition comprising one or more atypical antipsychotic or their pharmaceutically acceptable salts, one or more rate controlling polymers, which is in the form of an in-situ gelling composition and forms a depot upon administration in vivo upon contact with body fluids thereby providing a prolonged release of the active agent for extended periods of time.

In yet another aspect, the present invention provides a parenteral controlled release composition comprising one or more atypical antipsychotic or their pharmaceutically acceptable salts, one or more rate controlling polymers, and optionally one or more pharmaceutically acceptable excipients, which is in the form of an in-situ gelling composition and forms a depot upon administration in vivo upon contact with body fluids thereby providing a prolonged release of the active agent for extended periods of time.

The composition may release the atypical antipsychotic for over a period of at least 15 days, for example over a period of 1 month or over a period of 3 months.

In yet another aspect, the present invention provides a parenteral controlled release composition comprising lurasidone or its pharmaceutically acceptable salts, one or more rate controlling polymers, and optionally one or more pharmaceutically acceptable excipients, which is in the form of an in-situ gelling composition and forms a depot upon administration in vivo upon contact with body fluids thereby providing a prolonged release of the lurasidone for extended periods of time.

The composition may release the lurasidone or its pharmaceutically acceptable salts for over a period of at least 15 days, for example over a period of 1 month or over a period of 3 months.

Embodiments of the parenteral controlled release composition may include one or more of the following features. For example, the composition may be in the form of a solution or dispersion. The composition may include at least one solvent. The viscosity of the in-situ gelling composition is from about 100P to about 1000P and pH of the composition is from about 3.5 to about 6.5.

In another general aspect, the present invention provides a process for the preparation of a parenteral controlled release composition comprising one or more atypical antipsychotic or their pharmaceutically acceptable salts, one or more rate controlling polymers, and optionally one or more pharmaceutically acceptable excipients, wherein the composition provides a prolonged release of the atypical antipsychotics or salts thereof for extended periods of time, the process comprising:

i) dissolving a rate controlling polymer in a suitable solvent under continuous stirring;

ii) dispersing atypical antipsychotic agent or salts thereof into the solution of step i); and iii) filling the dispersion of step ii) in a suitable container and storing at room temperature.

In another general aspect there is provided a method for the prophylaxis or treatment of psychotic disorders such as neuropsychiatry (psychotic depression and other psychotic episodes) and neurodevelopmental disorders (especially Autistic spectrum disorders), neurodegenerative disorders, depression, mania, and in particular, schizophrenic disorders

(paranoid, catatonic, disorganized, undifferentiated and residual schizophrenia) and bipolar disorders and the like, comprising administering to said subject an effective amount of parenteral controlled release composition comprising lurasidone or its pharmaceutically acceptable salts, one or more rate controlling polymers, and optionally one or more pharmaceutically acceptable excipients.

DETAILED DESCRIPTION OF THE INVENTION:

Technical and scientific terms used herein have the meaning commonly understood by one of skill in the art to which the present invention pertains, unless otherwise defined.

Reference is made herein to various methodologies and materials known to those of skill in the art. Standard reference works setting forth the general principles of pharmacology include

Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th Ed., McGraw Hill

Companies Inc., New York (2001).

Any suitable materials and/or methods known to those of skill can be utilized in carrying out the present invention. However, preferred materials and methods are described. Materials, reagents and the like to which reference are made in the following description and examples are obtainable from commercial sources, unless otherwise noted. Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. The polymer concentration and solvent type are the most critical factors in determining the flowablity and the introduction of composition into the body using a syringe.

The inventors of the present invention have surprisingly found that the formulations prepared using the polymer as well as concentration disclosed in the context of the present invention achieve prolonged release of drug which leads to increased patient compliance along with improved syringibility due to low viscosity with appropriate selection of solvent.

The liquid based parenteral depot composition usually present with the possibility of a burst release of drug especially during the first few hours after injecting into the body. Therefore, in order to control the burst effect, the inventors of present invention evaluated three factors, i.e., the concentration of polymer in the solvent, the molecular weight of the polymer, and the solvent used and formulate the present parenteral controlled release composition.

The rate controlling polymer, according to the present invention includes a base polymer that is a pharmaceutically acceptable, biocompatible, biodegradable and/or bioerodible, thermoplastic polymer or copolymer which is substantially insoluble in an aqueous medium. Examples of rate controlling polymers include, polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyure thanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(amino acids) and copolymers, terpolymers and combinations thereof. Preferred polymers are polylactides, polyglycolides, polycaprolactones, polyanhydrides, and polyorthoesters. More preferably polymers are poly (lactic acid), poly (glycolic acid), poly (lactide-co-glycolic acid), poly(decalactone), polyecaprolactone, poly(DL-lactide), poly(DL-lactide-co-glycolide) and poly(DL-lactide-co-caprolactone). The most preferred polymer is poly(lactic-co-glycolic acid). The ratio of the lactide-to-glycolide in poly(lactic-co-glycolic acid) (PLGA) in the present invention are selected from the range of 90: 10 to 10:90. Preferably the ratio is 50:50, 65:35, 75:25, and 85: 15. As the ratio of the lactic acid increases the hydrophobicity of the polymer is increased as lactic is more hydrophobic than glycolic acid, consequently PLGA will absorb less water and degrade more slowly.

The amount of the rate controlling polymer present in the pharmaceutical composition may range from about 2% w/w to about 30% w/w relative to the total weight of the composition.

The antipsychotics may be selected from one or more of amisulpride, nemonapride, remoxipride, sultopride, tiapride, cinuperone, melperone, setoperone, iloperidone, ocaperidone, paliperidone, risperidone, lurasidone, perospirone, revospirone, tiospirone, ziprasidone, amperozide, aripiprazole, bifeprunox, brexpiprazole, cariprazine, amoxapine, asenapine, carpipramine, clocapramine, clorotepine, clotiapine, clozapine, flumezapine, fluperlapine, gevotroline, metitepine, mosapramine, olanzapine, quetiapine, tenilapine, zotepine, or pharmaceutically acceptable salts thereof.

The preferred atypical antipsychotic is lurasidone, or its pharmaceutically acceptable salts.

Examples of suitable solvents include substituted hetero cyclic compounds such as N-methyl pyrrolidone (NMP), 2-pyrrolidone; esters of carbonic acid and alkyl alcohols such as propylene carbonate, ethylene carbonate and dimethyl carbonate; alkyl esters of mono-, di- , and tricarboxylic acids such as 2-ethyoxyethyl acetate, ethyl acetate, methyl acetate, ethyl lactate, ethyl butyrate, diethyl malonate, diethyl glutonate, tributyl citrate, diethyl succinate, tributyrin, isopropyl myristate, dimethyl adipate, dimethyl succinate, dimethyl oxalate, dimethyl citrate, triethyl citrate, acetyl tributyl citrate, glyceryl triacetate, benzyl benzoate; alkyl ketones such as acetone and methyl ethyl ketone; alcohols such as solketal, glycerol formal, Benzyl alcohol and glycofurol; dialkylamides such as dimethylformamide, dimethylacetamide; dimethyl sulfoxide (DMSO) and dimethylsulfone; tetrahydrofuran; lactones such as e-caprolactone and butyrolactone; cyclic alkyl amides such as caprolactam; aromatic amides such as N,N-dimethyl-m-toluamide, and l-dodecylazacycloheptan-2-one; and mixtures and combinations thereof. The solvents must be biocompatible so that they do not cause severe tissue irritation or necrosis at the site of implantation. Furthermore, the solvent should be water miscible so that it will diffuse quickly into the body fluids and allow water to permeate into the polymer solution and cause it to jellify. Preferred solvents include N-methyl-2-pyrrolidone, benzyl benzoate, benzyl alcohol, 2-pyrrolidone, dimethylsulfoxide, ethyl lactate, and propylene carbonate, glycerol formal, and glycofurol. Typically, the parenteral controlled release composition of present invention includes about 10 wt % to about 90 wt %, more preferably about 40 wt % to about 80 wt % of a solvent.

The parenteral controlled release composition of the present invention when brought in contact with an aqueous environment, such as body or tissue fluids, the solvent dissipates or disperses into the aqueous or body fluid. Concurrently, the substantially insoluble biodegradable polymer precipitates or coagulates to form a flexible matrix or film which traps or encapsulates the biologically active agent and reduces the initial burst of biologically active agent released from the polymeric composition as it coagulates to form a solid implant. Once the solid implant is formed, the biologically active agent is released from the implant by diffusion or dissolution from within the polymeric composition and/or the biologically active agent is released as the matrix is biodegraded, bioeroded or bioabsorbed.

The viscosity of the final formulation plays an important role in patient compliance. The composition that is "syringable" has a low enough viscosity to load the syringe and inject a subject from the syringe without undue force. Therefore, the viscosity of final composition for delivery to a subject should be sufficiently fluid to be flowable. The viscosity of parenteral controlled release composition is about 100-lOOOP. The injection compositions according to the invention are preferably adjusted to an injection viscosity of less than 600P preferred.

Further, the inherent viscosity (abbreviated as "I.V."; units are in deciliters/gram) of the biodegradable polymer also play an important role to decide the viscosity of the final composition. The inherent viscosity of the biodegradable polymer is a measure of its molecular weight and degradation time (e.g., a biodegradable polymer with a high inherent viscosity has a higher molecular weight and longer degradation time). Typically, a biodegradable polymer with a high molecular weight provides a stronger matrix and the matrix takes more time to degrade. In contrast, a biodegradable polymer with a low molecular weight degrades more quickly and provides a softer matrix. Preferably, the biodegradable polymer has a molecular weight of about 5,000 to about 20,000, and the inherent viscosity, from about 0.10 dL/g to about 2 dL/g (as measured in chloroform).

At pH values within this range, local tissue toxic reactions are satisfactorily minimized or avoided, yet without adversely affecting the solubility of the active ingredient or its therapeutic activity.

In yet another embodiment, the present invention provides a parenteral controlled release composition comprising lurasidone or its pharmaceutically acceptable salts, one or more rate controlling polymers, and optionally one or more pharmaceutically acceptable excipients, wherein the composition forms a gel when placed in an aqueous physiological- type environment and releases the active agent for preferably over a period of 3 month.

These treatments reduce the risk of relapse in patient with psychotic disorders, who have difficulties adhering to oral medication regimens.

In yet another embodiment, the present invention provides a process of preparing a parenteral controlled release composition comprising one or more atypical antipsychotics or their pharmaceutically acceptable salts, one or more rate controlling polymers, and optionally one or more pharmaceutically acceptable excipients, wherein the composition provides prolonged release of the active agent(s) for extended periods of time, wherein process comprising following steps:

i) dissolving a rate controlling polymer in a suitable solvent under continuous stirring;

ii) dispersing atypical antipsychotic agent or salts thereof into the solution of step i); and iii) filling the dispersion of step ii) in a suitable container and storing at room temperature.

In another embodiment, the parenteral controlled release composition of the present invention comprise of one or more pharmaceutically acceptable excipient(s) selected from but not limited to a group comprising one or more solvents/cosolvents, preservatives, buffering agents, pH adjusting agents, or any other excipient known to the art that is soluble or miscible or dispersible in solvent(s), or mixtures thereof.

Examples of the suitable preservatives for the composition according to the invention may be selected from, but not limited to, benzyl alcohol, quaternary ammonium halides, phenylcarbinol, thimerosal, disodium edetate and phenyl ethyl alcohol. Examples of suitable buffers may include one or more of borate buffers, tartarate buffers, lactate buffers, citrate buffers, phosphate buffers (e.g. potassium phosphate monobasic), citric acid/phosphate buffers, carbonate/carbonic acid buffers, succinate/succinic acid buffers, and tris(hydroxymethyl)aminomethane /hydrochloric acid buffers and the like.

Examples of suitable pH adjusting agents for the composition according to the invention may be selected from, but not limited to, sodium hydroxide, hydrochloric acid, citric acid, acetic acid, fumaric acid, hydrochloric acid, malic acid, nitric acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, or combinations thereof. The composition of the present invention comprises an amount of a pH adjusting agent sufficient to adjust pH about 3.5 - 6.5.

The present invention also provides a kit. The kit may include a container and a syringe separately. The container includes a composition that includes the parenteral controlled release composition comprising atypical antipsychotics or salts thereof, at least one rate controlling polymer, and optionally at least one pharmaceutically acceptable excipient. The kit can preferably include instructions.

Other features of the invention will become apparent in the course of the following descriptions of exemplary embodiments which are given for illustration of the invention and are not intended to be limiting thereof.

Example 1

Process :

1) PLGA was weighed and dissolved in N-methyl pyrrolidone under continuous stirring,

2) Lurasidone was weighed and dispersed in the solution of step 1) and volume was made up with N-methyl pyrrolidone,

3) The dispersion of step 2) was filled in a suitable container and stored at room temperature. Example 2

Process:

1) PLGA was weighed and dissolved in N-methyl pyrrolidone under continuous stirring, 2) Lurasidone was weighed and dispersed in the solution of step 1) and volume was made up with N-methyl pyrrolidone,

3) The dispersion of step 2) was filled in a suitable container and stored at room temperature.

Example 3

Process:

1) PLGA was weighed and dissolved in N-methyl pyrrolidone under continuous stirring,

2) Lurasidone was weighed and dispersed in the solution of step 1) and volume was made up with N-methyl pyrrolidone,

3) The dispersion of step 2) was filled in a suitable container and stored at room temperature.

Example 4

Process:

1) PLGA was weighed and dissolved in N-methyl pyrrolidone under continuous stirring, 2) Lurasidone was weighed and dispersed in the solution of step 1) and volume was made up with N-methyl pyrrolidone,

3) The dispersion of step 2) was filled in a suitable container and stored at room temperature.

Example 5

Process:

1) PLGA was weighed and dissolved in benzyl benzoate under continuous stirring,

2) Lurasidone was weighed and dissolved in benzyl alcohol under continuous stirring at 65±5°C,

3) The solution of step 2) was cooled at room temperature,

4) The solution of step 1) was mixed with the solution of step 3) under continuous stirring,

5) The solution of step 4) was filled in a suitable container and stored at room temperature.

Example 6

Process:

1) PLGA was weighed and dissolved in Benzyl Benzoate under continuous stirring,

2) Lurasidone was weighed and dissolved in Benzyl alcohol under continuous stirring at 65±5°C,

3) The solution of step 2) was cooled at room temperature,

4) The solution of step 1) was mixed with the solution of step 3) under continuous stirring,

5) The solution of step 4) was filled in suitable container and stored at room temperature.

Claims

We Claim:

1. A parenteral controlled release composition comprising one or more atypical antipsychotic or their pharmaceutically acceptable salts, one or more rate controlling polymers, which is in the form of an in-situ gelling composition and forms a depot upon administration in vivo upon contact with body fluids thereby providing a prolonged release of the active agent for extended periods of time.

2. The parenteral controlled release composition as claimed in claim 1, wherein the composition releases the atypical antipsychotic for over a period of at least 15 days.

3. The parenteral controlled release composition as claimed in claim 1, wherein the composition releases the atypical antipsychotic for over a period of at least 1 month.

4. The parenteral controlled release composition as claimed in claim 1, wherein the composition releases the atypical antipsychotic for over a period of at least 3 months.

5. The parenteral controlled release composition as claimed in claim 1, wherein the composition is in the form of a solution or dispersion.

6. The parenteral controlled release composition as claimed in claim 1, wherein the viscosity of the in-situ gelling composition is from about 100P to about 1000P.

7. The parenteral controlled release composition as claimed in claim 1, wherein the pH of the composition is from about 3.5 to about 6.5.

8. The parenteral controlled release composition as claimed in claim 1, wherein the one or more atypical antipsychotic comprises one or more of amisulpride, nemonapride, remoxipride, sultopride, tiapride, cinuperone, melperone, setoperone, iloperidone, ocaperidone, paliperidone, risperidone, lurasidone, perospirone, revospirone, tiospirone, ziprasidone, amperozide, aripiprazole, bifeprunox, brexpiprazole, cariprazine, amoxapine, asenapine, carpipramine, clocapramine, clorotepine, clotiapine, clozapine, flumezapine, fluperlapine, gevotroline, metitepine, mosapramine, olanzapine, quetiapine, tenilapine, zotepine, and their pharmaceutically acceptable salts.

9. The parenteral controlled release composition as claimed in claim 1, the composition comprising lurasidone or its pharmaceutically acceptable salts, one or more rate controlling polymers, and optionally one or more pharmaceutically acceptable excipients, which is in the form of an in-situ gelling composition and forms a depot upon administration in vivo upon contact with body fluids thereby providing a prolonged release of the lurasidone for extended periods of time.

10. The parenteral controlled release composition as claimed in claim 1, wherein the rate controlling polymer comprises one or more of polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxy valerates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(amino acids) and copolymers, terpolymers and combinations thereof.

11. The parenteral controlled release composition as claimed in claim 1, wherein the composition comprises one or more of pharmaceutically acceptable excipient(s) selected from one or more of solvents/cosolvents, preservatives, buffering agents, pH adjusting agents, or mixtures thereof.

12. A process for the preparation of a parenteral controlled release composition, the process comprising:

i) dissolving a rate controlling polymer in a suitable solvent under continuous stirring;

ii) dispersing atypical antipsychotic agent or salts thereof into the solution of step i); and iii) filling the dispersion of step ii) in a suitable container and storing at room temperature.