FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
"PHARMACEUTICAL FORMULATION AND PROCESS FOR MANUFACTURING THEREOF"
2. APPLICANT:
(a) NAME: CIPLA LTD.
(b)NATIONALITY: Indian Company incorporated under the Companies Act, 1956
(c) ADDRESS: 289, Bellasis Road, Mumbai Central, Mumbai - 400 008, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be formed.

Related application:
This application is Complete Cognate Application for the Patent Application No. 527/MUM/2010 dated 26/02/2010; and Application No. 3299/MUM/2010 dated 03/12/2010.
Field of Invention:
The present invention relates to a pharmaceutical formulation that is a solid dosage form comprising an antipsychotic drug. There is also provided a process of preparing the solid dosage form and also the use of the said dosage form thereof in the treatment and / or prevention of disorders or conditions that respond to, or are alleviated by, the administration of the said antipsychotic drug.
Background and Prior Art:
Numerous drugs are known to exist which can be used for the treatment of psychotic disorders, such as schizophrenia (SZ), related SZ-spectrum disorders (including schizotypal personality disorder (SPD) and schizoaffective disorder (SD)), and bipolar disorders (BD). Most of these drugs fall into one of the two categories, typical (first generation) and atypical (second generation).
Although head to head studies carried out on large groups of patients, either in the acute phase or outpatient treatment, show that most atypical antipsychotic drugs are equally efficacious for positive symptoms, however there are few individual differences in response to specific drugs based on differences in drug pharmacology and metabolism, combined with genetic differences between patients. There are currently no ways to prove and identify which antipsychotic drug is optimal for a given patient. Thus, patients switch from one drug to another when response is not considered to be adequate or side effects are intolerable. This switching of medication incurs a variety of increased costs, both from economic and patient's acceptability point of view. On average, each patient may change medications three times before finding one that actually works. Additionally, the

current drugs have significant side-effects. This combination of side-effects and limited efficacy create a vast unmet need for selecting the optimal antipsychotic for each patient.
Aripiprazole is the international non-proprietary name of one such atypical antipsychotic drug. Aripiprazole is chemically named as 7-{4-[4-(2,3-dichlorophenyl)piperazin-l-yl]butoxy}-3,4-dihydroquinolin-2(lH)-one. Aripiprazole has the following structural formula:

It is a commercially marketed, pharmaceutically active substance useful for treatment of schizophrenia and bipolar disorder. It is disclosed in EP0367141/US Patent No. 5,006,528. The commercially marketed product is the free base of the above compound.
There are innumerous references towards the existence of various polymorphic forms of this molecule. Solid state aripiprazole was prepared in US Patent No. 5,006,528 by a twofold recrystallization of crude aripiprazole from ethanol resulting in colorless flake crystals having a melting point of 139-139.5°C. In an article of Aoki (Study on Crystal Transformation of Aripiprazole, The Fourth Japan-Korea Symposium on Separation Technology, p.937 ff (1996)), this solid state form was designated as Type I aripiprazole and identified as an anhydrate. Aoki also teaches that the Type I aripiprazole may be converted into a Type II aripiprazole by heating at 130-140°C for 15 hours. This product is also an anhydrate with a melting point of 150°C. When both Type I and Type II aripiprazole were recrystallized from an alcoholic solvent containing water up to 20%, the product was an aripiprazole hydrate labeled as Type III by Aoki. Type III aripiprazole can be converted into Type I by heating at 80°C. WO 03/26659 (EP 1330249) teaches that Type I aripiprazole, the alleged original solid form of aripiprazole, is significantly

hygroscopic. In an effort to find a form of aripiprazole having reduced hygroscopicity and better processing qualities, seven crystalline forms (A-G) were described.
In order to prevent the interconversion of Aripiprazole in to different polymorphic forms, formulations of Aripiprazole using different techniques like wet and dry granulations have been reported in the literature.
EP1808165 discloses methods of making tablets using direct compression or dry granulation via dry compaction technique. It further discloses that formulations prepared by direct compression prevent or reduce hydration and associated subsequent polymorphic transformations. However, direct compression is generally limited to those circumstances in which the active ingredient and excipients have physical characteristics suitable for forming pharmaceutically acceptable tablets. These physical characteristics include, but are not limited to, cohesive properties, good flowing properties, compressibility, and compactability to facilitate the formation of granules. Further, dry granulation often produces a higher percentage of fine granules, which can compromise the quality or create yield problems for the tablet.
WO2007081366 discloses method of making aripiprazole pharmaceutical compositions by wet granulation comprising: providing a mixture of aripiprazole, at least one diluent, at least one tablet binder, and water; blending the mixture to obtain a wet granulate; drying the wet granulate at a temperature of less than 70°C to obtain a dried granulate; and milling the dried granulate to obtain a milled dried granulate, with the proviso that the wet granulate is not milled prior to drying.
EP2036545 discloses a method of preparing Aripiprazole formulation using wet granulation technique wherein the drying step is carried out at an inlet temperature of about 70°C or less followed by milling the dried granulate, to prevent the conversion of Aripiprazole polymorphic form . However drying at such a low temperature would be time consuming, and milling may lead to some degree of superficial damage to the granulates so obtained which may eventually lead to manufacturing deformities in the product.

Bentham et. al. (Titled "Fluidized-bed jet milling of pharmaceutical powders", Institute of Particle Science & Engineering, University of Leeds, Revised 19 January 2004; accepted 19 January 2004; Available online 26 April 2004) describe about the milling of pharmaceutical powders by various means e.g. jet milling in fluidized bed equipments. However, jets in fluidized beds can cause intense interparticle collision, which may lead to some degree of surface damage, thereby leading to generally undesirable breakage and other critical issues.
It has now been found that, despite the availability and the knowledge of the above mentioned prior art processes, there still remains a difficulty to develop and formulate such sensitive product (like Aripiprazole solid dosage form) keeping into consideration the reduction in the conversion of the polymorphic forms and prevention of interparticle collision thereby leading to criticalities in the development and manufacture of the product. Hence, there still remains a need of a suitable process for manufacturing Aripiprazole solid dosage form, which would avoid the use of operating conditions that might induce the above mentioned criticalities.
Object of the Invention:
The object of the present invention is to provide a stable formulation of Aripiprazole.
Another object of the present invention is to provide a stable formulation of Aripiprazole by means of an improved process for manufacturing Aripiprazole solid dosage form so as to avoid manufacturing deformities.
Yet another object of the present invention is to provide an improved process for manufacturing Aripiprazole solid dosage form so as to reduce the polymorphic change.
Summary of the Invention:
According to one aspect of the present invention there is provided a stable formulation comprising Aripiprazole or pharmaceutically acceptable salt, solvate, derivatives, hydrate enantiomer, polymorph, or mixtures thereof.

According to the second aspect of the present invention, there is provided an improved
process of manufacturing Aripiprazole solid dosage form comprising
i) granulating the active ingredient with pharmaceutically acceptable excipients;
ii) drying the granules at low temperatures;
iii) sieving the granules;
iv) using the granules to obtain the desired dosage form.
According to the third aspect of the present invention, there is provided an improved
process of manufacturing Aripiprazole solid dosage form comprising
i) wet granulating the active ingredient with pharmaceutically acceptable excipients
comprising diluents and/ or disintegrants with binder;
ii) drying the granules at temperatures less than about 70°C;
iii) sieving the granules and lubricating the granules with lubricants;
iv) compressing the granules to form tablet.
According to the fourth aspect of the present invention, there is provided a solid dosage
form comprising Aripiprazole, with one or more pharmaceutically acceptable excipients
processed by:
i) granulating the active ingredient with one or more pharmaceutically acceptable
excipients;
ii) drying the granules at low temperatures;
iii) sieving the granules;
iv) using the granules to obtain the desired dosage form.
According to the fifth aspect of the present invention, there is provided a solid dosage
form comprising Aripiprazole and atleast one active with one or more pharmaceutically
acceptable excipients, wherein the said Aripiprazole portion of the dosage form is
processed by:
i) granulating the active ingredient with one or more pharmaceutically acceptable
excipients;
ii) drying the granules at low temperatures;
iii) sieving the granules;
iv) using the granules to obtain the desired dosage form.

According to the sixth aspect of the present invention there is provided a method of treatment using stable formulation comprising of Aripiprazole or pharmaceutically acceptable salt, solvate, derivatives, hydrate enantiomer, polymorph, or mixtures thereof.
According to the seventh aspect of the present invention, there is provided an improved process of manufacturing Aripiprazole solid dosage form for use in treating disorders or conditions that respond to, or are prevented, ameliorated or eliminated by, the administration of Aripiprazole.
According to the eighth aspect of the present invention, there is provided an improved process of manufacturing Aripiprazole solid dosage form for use in treatment of schizophrenia, bipolar disorder and clinical depression.
Detailed description of the invention:
Aripiprazole is well absorbed after oral administration of the formulation, with peak plasma concentrations occurring within 3 to 5 hours after dosing; having absolute oral bioavailability of 87%. However in cases wherein form conversion occurs due to hydration of Aripiprazole during formulation or storage, it leads to decrease in oral absorption and alters the bioavailability of the formulation. Having said that, stable Aripiprazole formulations may be obtained using non-aqueous solvents or mixtures thereof as granulation aid or by use of suitable process of manufacturing Aripiprazole solid dosage form comprising granulating the active ingredient with pharmaceutically acceptable excipients; drying the granules at low temperature followed by sieving the dried granules. For the sake of clarity, the dried granules are not milled (by use of conventional milling apparatus & processes known to person skilled in the art).
The granules so obtained by the above process may, further, be used to manufacture suitable dosage form, preferably solid dosage form. However, it will be well acknowledged by a person skilled in the art that the granules so obtained, may further be used to form liquid dosage form.

All throughout the specification, the terms "drug", "active", "active ingredient" or "Aripiprazole" may envisage not only their base form but also their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs, pharmaceutically acceptable esters or pharmaceutically acceptable prodrugs thereof. The said terms further denote any physical form, such as crystal forms like as described in WO 03/026659, Type-I, Type-11 crystals or amorphous form or anhydrous crystal forms like Form B, C, D, E, F, or G and a hydrate form denominated Form A. Novel crystals forms as described in WO 05/058835 like Form I, II, VII, VIII, X, XI, XII, XIV, XIX, and XX or the anhydrous forms like Form J or Form L as described in WO2007004061 all of which are incorporated herein by reference.
According to one aspect of the present invention there is provided a stable formulation of Aripiprazole using non-aqueous solvent as granulation aid.
A 'granulation aid' is defined as a liquid which, when mixed with the Aripiprazole and excipient(s), promotes adherence, or agglomeration, of the particles to form granules.
According to the present invention, non-aqueous solvents that may be used for granulation may preferably be selected from class III solvents due to their safety profile and permitted daily exposure [PDE] of 50 mg or more per day according to ICH guidelines on residual solvents. Examples of class III solvents that may be used include but are not limited to isopropyl alcohol, ethanol, ethyl acetate, acetone, butyl acetate, dimethyl sulfoxide or mixture thereof, preferably Isopropyl alcohol. Due to low boiling point of these solvents, the exposure of the drug to moisture is minimized.
According to another aspect of the present invention, there is provided an improved process comprising wet granulating the active ingredient with one or more pharmaceutically acceptable excipients; drying the granules at low temperature followed by sieving the dried granules so as to further use the granules into the desired dosage form.

The drying of the granules, according to the present invention, may be carried out at low temperatures, preferably, less than 70°C. More preferably, the granules may be dried at a temperature ranging between 500C to 70°C.
Following heating, the granules so obtained may be sieved and sifted through suitable mesh, preferably avoiding any milling process, so as to have uniformity in granules so obtained.
Accordingly, the improved process for manufacturing Aripiprazole solid dosage form, may comprise wet granulating the active ingredient with one or more pharmaceutically acceptable excipients; drying the granules at low temperature followed by sieving the dried granules and wherein no milling is carried out. Alternatively, the granules so obtained may be mixed, treated or blended with suitable pharmaceutically acceptable excipients so as to obtain the desired dosage form.
Preferably, the improved process of manufacturing Aripiprazole solid dosage form may comprise blending a mixture of Aripiprazole, at least one disintegrant, at least one binder, and water to obtain wet granules; drying the wet granules at a temperature less than 70°C to obtain dried granules; and sieving the dried granules and wherein no milling is carried out, followed by lubricating the granules with at least one lubricant and optionally other pharmaceutically acceptable excipient to the dried granules; and compressing the lubricated granules to form tablets.
Preferably, the improved process of manufacturing Aripiprazole solid dosage form may comprise blending a mixture of Aripiprazole, at least one binder, and water to obtain wet granules; drying the wet granules at a temperature less than 70°C to obtain dried granules; and sieving the dried granules and wherein no milling is carried out, followed by lubricating the granules with at least one lubricant and optionally other pharmaceutically acceptable excipient to the dried granules; and compressing the lubricated granules to form tablets.
Preferably, the improved process of manufacturing Aripiprazole solid dosage form may comprise blending a mixture of Aripiprazole, atleast one diluent, at least one binder, and/

or atleast one disintegrant to obtain wet granules; drying the wet granules at a temperature less than 70°C to obtain dried granules; and sieving the dried granules and wherein no milling is carried out, followed by lubricating the granules with at least one lubricant and optionally other pharmaceutically acceptable excipient to the dried granules; and compressing the lubricated granules to form tablets.
Preferably, the improved process of manufacturing Aripiprazole solid dosage form may comprise blending a mixture of Aripiprazole, atleast one diluent, at least one binder, and/ or atleast one disintegrant and water to obtain wet granules; drying the wet granules at a temperature less than 70°C to obtain dried granules; and sieving the dried granules and wherein no milling is carried out, followed by lubricating the granules with at least one lubricant and optionally other pharmaceutically acceptable excipient to the dried granules; and compressing the lubricated granules to form tablets.
The present invention also provides a solid dosage form comprising Aripiprazole with
one or more pharmaceutically acceptable excipients wherein the said dosage form is
processed by:
i) granulating the active ingredient with one or more pharmaceutically acceptable
excipients;
ii) drying the granules at low temperatures;
iii) sieving the granules;
iv) using the granules to obtain the desired dosage form.
Preferably, a solid dosage form, according to the present invention, may comprise
Aripiprazole and one or more pharmaceutically acceptable excipients wherein the said
dosage form is processed by:
i) wet granulating the active ingredient with pharmaceutically acceptable excipients
comprising diluents and/ or disintegrants with binder;
ii) drying the granules at temperatures less than about 70°C;
iii) sieving the granules and lubricating the granules with lubricants;
iv) using the granules to obtain the desired dosage form.

More preferably, a solid dosage form, according to the present invention, may comprise
Aripiprazole and one or more pharmaceutically acceptable excipients wherein the said
dosage form is processed by:
i) wet granulating the active ingredient with pharmaceutically acceptable excipients
comprising diluents and/ or disintegrants with binder;
ii) drying the granules at temperatures ranging between 50°C - 70°C;
iii) sieving the granules and lubricating the granules with lubricants;
iv) compressing the granules to form tablet.
Alternatively, the dosage form, according to the present invention, so produced may be seal coated. Still alternatively, the dosage form so produced may be seal coated and further film coated/ enteric coated (if required).
The present invention also provides a solid dosage form comprising Aripiprazole and
atleast one active with one or more pharmaceutically acceptable excipients, wherein the
said Aripiprazole portion of the dosage form is processed by:
i) granulating the active ingredient with one or more pharmaceutically acceptable
excipients;
ii) drying the granules at low temperatures;
iii) sieving the granules;
iv) using the granules to obtain the desired dosage form.
Preferably, a solid dosage form, according to the present invention, may comprise
Aripiprazole and atleast one active with one or more pharmaceutically acceptable
excipients, wherein the said Aripiprazole portion of the dosage form is processed by:
i) wet granulating the active ingredient with pharmaceutically acceptable excipients
comprising diluents and/ or disintegrants with binder;
ii) drying the granules at temperatures less than about 70°C;
iii) sieving the granules and lubricating the granules with lubricants;
iv) using the granules to obtain the desired dosage form.

More preferably, solid dosage form, according to the present invention, may comprise
Aripiprazole and atleast one active with one or more pharmaceutically acceptable
excipients, wherein the said Aripiprazole portion of the dosage form is processed by:
i) wet granulating the active ingredient with pharmaceutically acceptable excipients
comprising diluents and/ or disintegrants with binder;
ii) drying the granules at temperatures ranging between 50°C - 70°C;
iii) sieving the granules and lubricating the granules with lubricants;
iv) compressing the granules to form tablet.
The solid dosage form, according to the above aspect, comprising atleast one active other than Aripiprazole may be processed through granulation (including dry granulation; wet granulation not limiting to aqueous and non-aqueous granulation; melt granulation); direct compression; melt extrusion (e.g. use of extruders); Extrusion & Spheronization; and other processes known to person skilled in the art and are not intended to limit the scope of the invention.
The above atleast one active, may comprise one or more of antipsychotic first generation drugs like butyrophenone class (like haloperidol, droperidol, etc); phenothiazine class (like chlorpromazine, fluphenazine, perphenazine, prochlorperazine, thioridazine, trifluoperazine, mesoridazine, promazine, periciazine, triflupromazine, levomapromazine, promethazine, pimozide, etc); thioxanthene class (chlorprothixene, clopenthixol, flupenthixol, thiothixine, zuclopenthixol etc.); second generation drugs like clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride, asenapine, Paliperidone, Iloperidone, zotepine, sertindole, etc.
Further, according to the present invention, the solid dosage form may comprise uncoated or coated particles comprising the active substance and/or one or more pharmaceutically acceptable excipients sensitive to environmental influences and in particular, sensitive to oxidation, environment pH , processing parameters and the like.
As used herein, by a "pharmaceutically acceptable carrier or excipient" is meant any pharmaceutically acceptable material which is compatible with the active ingredients, or pharmaceutically acceptable salts thereof, and which is not deleterious to the patient.

Such carriers or excipients are well known in the art and examples include one or more diluents/ bulking agents/fillers, binders, disintegrants, lubricants, glidants, colorants, coating agents, surfactants, etc.
As discussed above, the pharmaceutically acceptable excipients may comprise diluents/ bulking agents/ fillers such as microcrystalline cellulose, powdered cellulose, sugar compressible, lactose, fructose, lactitol, saccharose, sorbitol, mannitol, dextrates, dextrins, dextrose, maltodextrin, croscarmellose sodium, starch, pregelatinized starch and mixtures thereof. Preferably, the diluent to be added in the solid dosage form may range from 5% to 80% by weight of the dosage form.
Examples of binders or binding agents, according to the present invention, may comprise methyl cellulose, hydroxylpropyl cellulose (HPC), hydroxylpropyl methyl cellulose (HPMC), starch, polyvinyl pyrrolidone (PVP), gelatin, gum Arabic, ethyl cellulose, polyvinyl alcohol, tragacanth, sodium alginate and equivalents thereof. Preferably, the binder to be added in the solid dosage form may range from 1% to 15% by weight of the dosage form.
Examples of the disintegrants, according to the present invention, may comprise microcrystailine cellulose, hydroxylpropyl cellulose (HPC), low density HPC, carboxymethylcellulose (CMC), sodium CMC, calcium CMC, croscarmellose sodium, crospovidone, starch, crystalline cellulose, sodium starch glycollate, hydroxylpropyl starch and equivalents thereof. Preferably, the disintegrant to be added in the solid dosage form may range from 1% to 10% by weight of the dosage form.
Examples of suitable glidants and lubricants, according to the present invention, which includes, but are not limited to stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated castor oil, sucrose esters of fatty acid, microcrystailine wax, microcrystailine cellulose, colloidal silicon dioxide and equivalents thereof. Preferably, the glidants and lubricants to be added in the solid dosage form may range from 0.1% to 5% each by weight of the formulation.

It may be well acknowledged to a person skilled in the art that the disintegrant and/or granulation aid may be present inside the granules (i.e. intragranular) and/or outside the granules (i.e. extragranular). Preferably, the disintegrant and/or granulation aid may be present intragranularly however, which does not exclude the possibility that a portion of the disintegrant and/or granulation aid is present outside the granules).
Preferably, according to the present invention, the granules are formed in the presence of a granulating solvent (i.e. using a "wet granulation" process). Preferably the granulating solvent is water and/or other aqueous or non-aqueous solvents such as ethanol, isopropanol, etc, preferably water. The solvent can be added after mixing of the drug with the diluent/ bulking agent/ filler and/or binder. Preferably, just sufficient solvent to enable granulation is used. Preferably, the solvent is removed after formation of the granules, e.g. by drying through various techniques known to a person skilled in the art.
Preferably, according to the present invention, after formation the granules (e.g. the dried granules and/or the wet granules) are sieved to a particle size suitable for use in tablets or capsules, (e.g. for dry granules). For example, the granules can be sieved such that they pass through sieve or screen with a specific mesh size.
The present invention further provides the solid dosage form comprising Aripiprazole and one or more pharmaceutically acceptable excipients manufactured according to the present invention that may be administered in the form but not limited to that of oral tablets, capsules, pills, sachets, extrudates, and other forms of dosage known to a person skilled in the art.
Accordingly, the present invention further provides the solid dosage form comprising Aripiprazole and atleast one active together with one or more pharmaceutically acceptable excipients manufactured according to the present invention that may be administered in the form but not limited to that of oral tablets, capsules, pills, sachets, extrudates, and other forms of dosage known to a person skilled in the art.
The present invention still further provides for a method of treatment and/or prophylaxis of the psychotic disorders, such as schizophrenia (SZ), related SZ-spectrum disorders

(including schizotypal personality disorder (SPD) and schizoaffective disorder (SD)), and bipolar disorders (BD) and other related disorders by administering a therapeutically effective amount of the solid dosage form manufactured according to the present invention to a mammal in need thereof in a suitable therapeutic regimen.
It can be appreciated from the above mentioned method of treatment description in accordance with the present invention that it can be beneficial to provide, recommend or label a solid dosage form according to the present invention for administration with one or more other therapeutically active compounds used for treatment of Schizophrenia. The following example is for the purpose of illustration of the invention only and is not intended in any way to limit the scope of the present invention.
Formula 1:

Sr.
No. Ingredients Quantity [mg/tablet]
1. Aripiprazole 5.00
2. Lactose Monohydrate 67.00
3. Microcrystalline Cellulose (AvicelPH l0l) 12.47
4. Corn Starch 3.00
5. Hydroxy Propyl Cellulose (Klucel LF) 0.60
6. Isopropyl alcohol q.s.
7. Corn Starch 6.40
8. Magnesium Stearate 0.50
Total 95.00
Process:
1. All the ingredients were sifted through specified sieves.
2. Klucel LF was dissolved in Isopropyl Alcohol and added on to step 1 blend to form granules.

3. Granules obtained were dried, blended and lubricated.
4. Lubricated granules were compressed into tablets.
Formula 2:

Sr. No. Ingredients Quantity [mg/tablet]
1. Aripiprazole 5.00
2. Lactose Monohydrate 64.27
3. Corn Starch 12.00
4. Polyethylene glycol 6000 6.00
5. AvicelPH 101 3.20
6. Hydroxy Propyl Cellulose (Klucel LF) 2.00
7. Croscarmellose sodium 2.00
8. Color 0.03
9. Magnesium Stearate 0.50
Total 95.00
Process:
1. All the ingredients were sifted through specified sieves.
2. Except lubricant, all the sifted ingredients were blended and then added to hot melt granulator.
3. Granules obtained were sized and lubricated.
4. Lubricated granules were compressed into tablets.
Formula 3:

Sr. No. Ingredients Quantity per tablet
5 mg 10 mg 15 mg 30 mg
Dry Mix
1. Aripiprazole 5.00 10.00 15.00 30.00
2. Lactose Monohydrate 29.94 59.88 89.82 179.64

3. Microcrystalline Cellulose 1.60 3.20 4.80 9.60
4. Corn Starch 6.00 12.00 18.00 36.00
Binder
5. Hydroxy Propyl Cellulose (Klucel LF) 1.00 2.00 3.00 6.00
6. Purified water q. s. q. s. q. s. q. s.
Extragranular
7. Iron oxide red 0.01 0.02 0.03 0.06
8. Corn Starch 3.20 6.40 9.60 19.20
9. Low Hydroxy Propyl Cellulose (LH PC LH11) 2.50 5.00 7.50 15.00
10. Colloidal silicon dioxide 0.50 1.00 1.50 3.00
Lubrication
11. Magnesium Stearate 0.25 0.50 0.75 1.50
Total 50.00 100.00 150.00 300.00
Process:
1. A premix was made by mixing Aripiprazole and Lactose Monohydrate through suitable sieve.
2. Microcrystalline Cellulose and corn starch were sifted through specified sieves and loaded alongwith premix in the fluidized bed equipment (FBE).
3. Klucel LF was dissolved in purified water & the binder was sprayed on to powder to form granules.
4. The wet granules were dried in fluid bed drier with an inlet temperature between 55°C to 60 °C and the dried granules were sieved through 30# by using vibratory sifter.
5. Color is mixed with corn starch and sifted through specified sieve and LHPC LH11 is mixed with colloidal silicon dioxide and sifted through sieve.
6. The dried granules were then blended with the color mix followed by lubrication with magnesium stearate.
7. The above lubricated blend was then finally compressed into tablets.

It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the spirit of the invention. Thus, it should be understood that although the present invention has been specifically disclosed by the preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and such modifications and variations are considered to be falling within the scope of the invention.
Jt is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to "a diluent" includes a single diluent as well as two or more different diluents, reference to a "disintegrant" refers to a single disintegrant or combination of two or more disintegrants, and the like.

We claim:
1. A stable formulation comprising Aripiprazole or pharmaceutically acceptable salt, solvate, derivatives, hydrate enantiomer, polymorph, or mixtures thereof.
2. A stable formulation comprising Aripiprazole or pharmaceutically acceptable salt, solvate, derivatives, hydrate enantiomer, polymorph, or mixtures thereof with one or more pharmaceutically acceptable excipients processed by:
i) granulating the active ingredient with pharmaceutically acceptable excipients;
ii) drying the granules at low temperatures;
iii) sieving the granules;
iv) using the granules to obtain the desired dosage form.
3. A stable formulation as claimed in claim 1 or 2, wherein the desired dosage form is solid dosage form.
4. An improved process of manufacturing Aripiprazole solid dosage form
comprising
i) granulating the active ingredient with pharmaceutically acceptable excipients;
ii) drying the granules at low temperatures;
iii) sieving the granules;
iv) using the granules to obtain the desired dosage form.
5. An improved process as claimed in claim 4, comprising
i) granulating the active ingredient with pharmaceutically acceptable excipients
comprising diluents and/ or disintegrants and/ or binder;
ii) drying the granules at temperatures less than about 70°C;
iii) sieving the granules and lubricating the granules with lubricants;
iv) compressing the granules to form tablet.
6. A stable formulation as claimed in claim 1 to 3, wherein the said solid dosage
form is processed by:
i) granulating the active ingredient with one or more pharmaceutically acceptable

excipients; ii) drying the granules at low temperatures; iii) sieving the granules; iv) using the granules to obtain the desired dosage form.
7. A stable formulation as claimed in claim 6, comprising:
i.) granulating the active ingredient with pharmaceutically acceptable excipients
alongwith granulation aid;
ii) drying the granules at temperatures less than about 70°C;
iii) sieving the granules and lubricating the granules with lubricants;
iv) compressing the granules to form tablet.
8. A stable formulation as claimed in claim 6 or 7, wherein the granulation aid is a non-aqueous solvent.
9. An improved process as claimed in claim 4 and 5, comprising:
i) blending a mixture of Aripiprazole, atleast one diluent, at least one binder, and/
or atleast one disintegrant to obtain granules;
ii) drying the granules at a temperature less than 70°C to obtain dried granules;
and iii) sieving the dried granules and wherein no milling is carried out.
10. An improved process as claimed in claim 4 and 5, comprising:
i) blending a mixture of Aripiprazole, at least one disintegrant, at least one binder,
and water to obtain wet granules;
ii) drying the wet granules at a temperature less than 70°C to obtain dried
granules;
iii) sieving the dried granules wherein no milling is carried out;
iv) lubricating the granules with at least one lubricant; and
v) compressing the lubricated granules to form tablets. 11. An improved process as claimed in claim 4 and 5, comprising:
i) blending a mixture of Aripiprazole, at least one binder, and water to obtain wet
granules;

ii) drying the wet granules at a temperature less than 70°C to obtain dried
granules;
iii) sieving the dried granules and wherein no milling is carried out,
iv) lubricating the granules with at least one lubricant; and
v) compressing the lubricated granules to form tablets.
12. A solid dosage form comprising Aripiprazole and atleast one active with one or
more pharmaceutically acceptable excipients, wherein the said Aripiprazole
portion of the dosage form is processed by:
i) granulating the active ingredient with one or more pharmaceutically acceptable
excipients;
ii) drying the granules at low temperatures;
iii) sieving the granules;
iv) using the granules to obtain the desired dosage form.
13. A stable formulation as substantially described herein with reference to the accompanying examples.
14. An improved process as substantially described herein with reference to the accompanying examples.
15. A solid dosage form as substantially described herein with reference to the accompanying examples.