F0RM2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. Title of the invention. - EXTENDED RELEASE FORMULATION OF
VENLAFAXINE HYDROCHLORIDE

2. Applicant(s)
(a) NAME :
(b) NATIONALITY
(c) ADDRESS :

ALEMBIC LIMITED
An Indian Company.
Alembic Road, Vadodara - 390 003, Gujarat, India.

3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed:


- 8 SEP 2OO5

I
FIELD OF THE INVENTION:
This invention relates to a pharmaceutical composition of extended release formulation comprising hard gelatin capsule containing therapeutically effective amount of mini-tablets wherein each mini-tablet comprises venlafaxine hydrochloride, microcrystalline cellulose, binder and optionally conventional excipients.
BACKGROUND AND PRIOR ART
The use of hydrophobic polymers to produce extended or controlled release pharmaceutical composition is known in the art. For extending the release, the solid dosage form of mini-tablets comprising a drug is coated with hydrophobic polymer and pore forming agent. As soon as solid dosage form comes in contact with surrounding media, the pores are formed and the drug is diffused through these pores. Control of the rate of release benefits therapy by producing constant blood plasma levels of the active ingredient and by decreasing the frequency of administration, thereby improving patient compliance to the dosage regimen. The present invention provides a pharmaceutical composition of extended release capsule containing mini-tablets of venlafaxine hydrochloride suitable for once daily administration to human subjects.
The invention relates to an extended release pharmaceutical formulation for once daily administration, in particular to a controlled release pharmaceutical formulation of venlafaxine hydrochloride.
Several extended release drug delivery system adapted for the delivery of venlafaxine hydrochloride are known in the prior art.
U.S. Pat. No. 4,535,186 describes a class of hydroxycycloalkanephenethyl amines as being useful antidepressants and exemplifies the compound now known as venlafaxine hydrochloride as one of the suitable species.
Venlafaxine, is chemically named as (R/S)-1-[2-(dimethylamino)-1-(4- methoxyphenyl) ethylj-cyclohexanol. Presently venlafaxine hydrochloride is administered to adults as conventional immediate release tablets or as 24 hours extended-release multiparticulate capsules. Venlafaxine hydrochloride is approved for sale in various countries including the United States of America under the brand name EFFEXOR.RTM. (Wyeth Ayerst). It is available as an immediate release tablet and as an extended release capsule under the

brand name EFFEXOR.RTM. (Wyeth Ayerst) and EFFEXOR XR.RTM. (Wyeth Ayerst), respectively.
Venlafaxine hydrochloride is very soluble in water. It is known that it is very difficult to develop a pharmaceutical form with a very slow dissolution rate of freely soluble drug.
U.S. Pat. No. 6274171 and related EP 0797991 disclose encapsulated extended release formulations for venlafaxine hydrochloride. A once daily, encapsulated extended release dosage form is disclosed that provides a flattened drug plasma profile and reduces the adverse side effects. The encapsulated dosage form is taught to comprise spheroids of venlafaxine hydrochloride, microcrystalline cellulose, and hydroxypropylmethylcellulose (HPMC). These spheroids are coated with a mixture of ethyl cellulose and HPMC. By providing an appropriate amount of the coating, the desired blood plasma profile can be obtained.
U.S. Pat. No. 6274171 and EP 0797991 also state that forming an extended release dosage from of venlafaxine hydrochloride was difficult in part due to the high water solubility of the hydrochloride salt. In fact, these patents disclose that "[n]umerous attempts to produce extended release tablets by hydrogel technology proved to be fruitless because the compressed tablets were either physically unstable (poor compressibility or capping problems) or dissolved too rapidly in dissolution studies." Unlike the encapsulated extended release formulations described in these patents, a hydrogel extended release venlafaxine hydrochloride tablet is taught to typically exhibit a dissolution profile wherein 40%-50% is released within 2 hours, 60%-70% is released within 4 hours, and 85%-100% is released within 8 hours.
W099/22724 also discloses encapsulated venlafaxine hydrochloride extended release dosage forms. These formulations differ from those in U.S. Pat. No. 6274171 and EP 0797991 in that the spheroid is substantially free of HPMC.
Although a venlafaxine extended release capsule has been produced, it would be advantageous to provide a less complicated dosage form that nonetheless provides extended release of venlafaxine.
W094/27589 and WO01/37815 describe osmotic dosage forms containing venlafaxine hydrochloride.

WO04/12699 and related US 20040096501 teach the use of dual retard technique to effectively control the release rate of modified release active ingredient by using small quantity of release controlling; agents. This dual retard technique thus sufficiently reduces the size of the dosage forrn> which is convenient for swallowing. The dosage form comprises of a) Micro matrix particles containing high solubility active ingredient and one or more hydrophobic release controlling agent, b) Coating of Micro matrix particles with one or more hydrophobic release controlling agents.
US 20030190354 discloses an extended release composition comprising as active compound venlafaxine hydrochloride in a matrix tablet dosage form, in which venlafaxine hydrochloride is mixed with a combination of hydrophilic and hydrophobic matrix forming components. The matrix components are suitably combination of high and low viscosity grades hydroxyl propyl methyl cellulose, ethyl cellulose, glyceryl behenate and methyl cellulose. Two granulation methods were used for the production of the tablets: the first was a regular one step granulation process, in which all excipients were blended together with the active, then wet granulated with Kollidon SR, dried, milled and compressed into oval shape scored tablets. The second granulation process was a two step process, the first was wet granulation of the active material, which was blended with the hydrophobic components selected from Ethocel or Compritol. Later on, the milled granulate was mixed with the hydrophilic components, the methocels and the lubricating components, syloid 244 and Mg stearate.
WO03/55475 teaches the controlled release formulation of venlafaxine. The pharmaceutical formulation of the present invention comprises for example a core consisting of an active drug which may be advantageously in amorphous form, polyvinylpyrrolidone, a combination of two hydrophilic polymers having different viscosity and optionally other commonly used ingredients for solid dosage forms. The core is coated with a polymeric coating comprising a combination of two polymers having different water permeability. A plasticizer and other commonly used ingredients for film coating may be optionally added thereto. The combination of the carriers i.e. the water soluble polymer, polyvinylpyrrolidone and the low viscosity hydrophilic polymer has a double effect and the advantage that it stabilizes the amorphous form of the active ingredient and simultaneously modifies the release of the amorphous active ingredient in such a way that it is sustained, repeatable and independent of the amorphous or polymorphous form of the active ingredient, its particle size and specific surface area.

WO 03/53402 and related US 2004133982 discloses zero-order sustained release dosage forms. A solid dosage form comprising a matrix core comprising intragranular ethylcellulose and a water soluble active agent granulated and compressed together with extragranular ethyl cellulose and a film coating comprising a hydrophobic polymer wherein the film coating completely encases the matrix core. This invention also relates to a process for manufacturing a zero-order sustained release tablet containing a water-soluble active agent, comprising the steps of :(a) preparing a first admixture comprising the active agent and intragranular ethylcellulose;(b) granulating the first admixture in order to obtain a granular product;(c) preparing a second admixture comprising extragranular ethylcellulose;(d) preparing a third admixture comprising the granular product and the second admixture;
Extended release preparation of drugs are advantageous in the administration, frequency can be reduced by maintaining constant plasma concentration of drug over an extended period of time to ensure sustained effect of active ingredient.
OBJECTIVES OF THE INVENTION
It is an object of the present invention to provide an extended release of the active ingredient from the pharmaceutical composition, which has blood plasma levels above minimum therapeutic concentration over extended period of time.
Another object of the present invention is to provide extended release pharmaceutical composition for once daily dosage form.
Yet another object of the present invention is to provide an extended release pharmaceutical composition, which releases the active ingredient in predetermined manner.
Yet another object of the present invention is to produce the formulation by a conventional method so as to reduce the process time.
Yet another object of the present invention is to develop extended release formulation of venlafaxine hydrochloride which is bioequivalent to effexor XR by conventional method comprising compression and coating.

SUMMARY OF THE INVENTION:
Accordingly, the present invention relates to an extended release pharmaceutical formulation comprising venlafaxine hydrochloride, diluent, water-soluble component and water insoluble polymer and other pharmaceutical acceptable excipients.
The components are selected in such a way to give extended release of the venlafaxine hydrochloride in a predetermined manner.
Preferably, the present invention relates to the extended release formulation which comprises from about 40% to about 80% by weight of a venlafaxine hydrochloride; from about 25% to about 45% of microcrystalline cellulose and from about 0.5% to about 10% polyvinyl pyrrolidone of the total weight of composition. The coating on mini-tablet comprises of from about 50% to about 95% ethylcellulose and from about 3% to about 50% of plasdone S-630 copolyvidonium (ISP technologies) of the total weight of the composition.
More preferably the present invention relates to the extended release formulation which comprises from about 48% to about 68% by weight of a venlafaxine hydrochloride; from about 26% to about 38% of microcrystalline cellulose and from about 2% to about 9% of polyvinyl pyrrolidone of the total weight of composition. The coating on mini-tablet comprises of from about 65% to about 95% ethylcellulose and from about 5% to about 40% of plasdone S-630 copolyvidonium of the total weight of the composition.
Still more preferably the present invention relates to the extended release formulation which comprises from about 57% to about 62% by weight of a venlafaxine hydrochloride; from about 27% to about 32% of microcrystalline cellulose and from about 2.5% to about 5.5% of polyvinyl pyrrolidone of the total weight of composition. The coating on mini-tablet comprises of from about 70% to about 80% ethylcellulose and from about 20% to about 30% of plasdone S-630 copolyvidonium of the total weight of the composition.
Preferably, the invention relates to extended release composition in the form of mini-tablets which are incorporated in hard gelatin capsules containing a therapeutically effective amount of the mini-tablets comprised of venlafaxine hydrochloride, microcrystalline cellulose, polyvinyl pyrrolidone and optionally conventional excipients and further coating of mini-tablets comprising of ethyl cellulose and plasdone S630

copolyvidonium (ISP technologies). The tablets of the invention exhibit specific dissolution profiles, especially with venlafaxine HCI.
According to the present invention, the extended release formulation may be prepared by functional coating method, the said method comprising steps of:
i. Blending the venlafaxine hydrochloride and diluent.
ii. Granulating the blended mixture with an aqueous and non-aqueous solution of
binder and drying it. iii. Lubricating the dried granules and compressing into tablets of appropriate
shape (3-6 mm in diameter), iv. Coating the tablets with an aqueous or non-aqueous dispersion of water insoluble
and water soluble component, v. Filling coated mini tablets obtained in step (iv) into capsule of appropriate size.
Such 12, 6, 3 mini-tablets are filled into pharmaceutically acceptable capsule to form 150 mg, 75 mg and 37.5mg strengths respectively of venlafaxine.
DETAILED DESCRIPTION OF THE INVENTION
In an embodiment of the present invention, the hard gelatin capsule comprises of film coated mini-tablets. These mini-tablets comprised of active ingredient, binder and water-soluble component and optionally conventional excipients. These mini-tablets are coated with combination of water-soluble and waters insoluble components.
According to the present invention, the pharmaceutical composition contains venlafaxine hydrochloride as an active ingredient. The venlafaxine hydrochloride may be present in an amount from about 40 % to about 80%, preferably from about 48% to about 68% by weight, more preferably from about 57% to about 62% of the total weight of extended release composition.
Further, venlafaxine hydrochloride may be present in an amount from 12.5mg to 400mg per capsule.
According to yet another embodiment of the present invention, the mini-tablet contains microcrystalline cellulose as diluent. Microcrystalline cellulose may be present in an amount from about 25 % to about 45%, preferably from about 26% to about 38% by

weight, more preferably from about 27% to about 32% of the total weight of extended release composition.
According to another embodiment of the present invention, the mini-tablet contains polyvinyl pyrrolidone as binder. Polyvinyl pyrrolidone may be present in an amount from about 0.5 % to about 10%, preferably from about 2% to about 9% by weight, more preferably from about 2.5% to about 5.5% of the total weight of extended release composition.
In addition to the above ingredients, pharmaceutical grade magnesium stearate/stearic acid as a glidant, talc as an anti-adherent and colloidal silicion dioxide as a lubricant are included in the mini-tablet. Preferably, magnesium stearate/stearic, talc and colloidal silicion dioxide are present in amounts in the range of 3% to 6% by weight either alone or in combination.
In an embodiment of the present invention, the coating on mini-tablet comprises of water insoluble polymer and water-soluble component. The water insoluble polymer is selected from the group consisting of cellulose ether such as ethylcellulose, a cellulose ester such as cellulose acetate, methacrylic derivatives available from Rohm Pharma under the trade name "Eudragit.RTM."RL, RS and NE, etc. In a preferred embodiment, the water insoluble polymer is ethyl cellulose present in an amount from about 50% to about 95% by weight of the functional coating of extended release composition.
In an embodiment of the present invention, the coating on mini-tablet also contains water-soluble component. The water soluble component is selected from the group consisting of Plasdone S-630 copolyvidonum (ISP technologies), hydrated colloidal silica, sucrose, mannitol or any other substance capable of playing the same role. In preferred embodiment, the water soluble component is Plasdone S-630 copolyvidonum (ISP technologies) is present in an amount from about 3% to about 50% by weight of the functional coating of extended release composition.
Ethyl cellulose, an ethyl ether of cellulose, is a long-chain polymer of b-anhydroglucose units joined together by acetal linkages. It is tasteless, free flowing, white to light tan colored powder. It is a stable, slightly hygroscopic material. It is practically insoluble in glycerin, propylene glycol and water. Ethylcellulose that contains less than 46.5% of ethoxyl groups is freely soluble in chloroform, methyl acetate and tetrahydrofuran and in

mixtures of aromatic hydrocarbons with ethanol (95%). Ethylcellulose that contains not less than 46.5% of ethoxy groups is freely soluble in chloroform, ethanol (95%), ethyl acetate, methanol and toluene. It is chemically resistant to alkalis, both dilute and concentrated and to salt solutions, although it is more sensitive to acidic materials than are cellulose esters. Ethyl cellulose polymers exhibit good stability within the pH range of 3 to 11, so they can be used vvith both acidic and alkaline ingredients.
The viscosity of ethyl cellulose is measured typically at 25°C using 5%w/v ethylcellulose dissolved in a solvent blend of 80% toluene: 20% ethanol (w/w). Different grades of ethylcellulose are ethocel std. 4 premium, ethocel. std 7FP premium, ethocel. std. 7 premium, ethocel std 10FP premium, ethocel std 10P premium, ethocel std 20P premium, ethocel std 45P premium, ethocel std 100FP premium, ethocel 100P having viscosity range of 3-5.5 cP, 6-8cP, 6-8cP, 9-11 cP, 9-11cP, 18-22cP, 41-49cP, 90-110cP, 90-110cP respectively. The viscosity of an ethylcellulose solution increases with an increase in ethylcellulose concentration- The viscosity of such solutions depends almost entirely on the alcohol content and is independent of toluene. In addition, nonpharmaceutical grades of ethylcellulose that differ in their ethoxyl content and degree of polymerization are available. Ethyl cellulose is prepared by treating purified cellulose with an alkaline solution, followed by ethylation of the alkali cellulose with chloroethane.
Plasdone S-630 copolyvidonum (ISP technologies) is a synthetic water-soluble copolymer consisting of N-vinyl-2-pyprrolidine and vinyl acetate in a random 60:40 ratio. Plasdone S-630 copolyvidonum has low hygroscopicity. At 50% RH level, Plasdone S-630 copolyvidonum gains less than 10% weight and does easily desorb the gained moisture. It is an excipient of Choice for moisture sensitive drugs.
The K-value for Plasdone S-630 copolyvidonum is specified between 25.4 and 34.2. The K-value is calculated from the kinematic viscosity of a 1 % aqueous solution and hence is related to the average molecular weight of the polymer.
Plasdone S-630 copolyvidonum is a highly effective film forming adhesive. It is used primarily as a tablet binder, although its unique properties make it useful in the formulation and coating of a variety of pharmaceutical dosage forms.
Plasdone S-630 copolyvidonum is soluble in many solvents and can be used in non¬aqueous granulation or coatings. It is supplied as a free-flowing spray-dried powder to

ensure maximum handling efficiency. Spray drying results in spherical particles with tightly controlled particle size distribution. The particle morphology is responsible for the excellent powder flow properties, which aids blending with other excipients.
According to a process for making the composition of the present invention, the venlafaxine hydrochloride is blended with microcrystalline cellulose and granulated using binder solution. These granules are then compressed into mini-tablets. The resulting mini-tablets are then coated with extended release polymer.
In an embodiment of the present invention, the functional coating is done by dissolving ethylcellulose and plasdone S 630 copolyvidonum in a solvent such as ethyl alcohol. The resulting solution is sprayed onto the mini-tablet cores, using a coating pan or a perforated turbine or a fluidized bed apparatus.
In an embodiment of the present invention, the weight ratio of functional coating/tablet is comprised e.g. between 0.02 and 0.15, preferably between 0.06 and 0.12.
The mini-tablet size ranges between 3-6 mm in diameter.
Preferably, venlafaxine hydrochloride and diluent are sifted through suitable mesh sieve and the sifted mass is blended using high shear mixture and the blended mass is granulated with aqueous or non-aqueous binder solution and the granulated mass is dried until the moisture content is less than 4% w/w and the dried mass is passed through suitable mesh sieve and this granules are lubricated with lubricants, glidants, antiadherants. The lubricated granules are compressed into tablets of appropriate size (3 - 6mm in diameter). The tablets are further coated with coating of water soluble and water insoluble component. These film-coated mini-tablets are filled into hard gelatin capsule.
The present invention is illustrated by the following examples.

EXAMPLES
General procedure for the preparation of extended release capsule containing mini-tablets
Venlafaxine hydrochloride and microcrystalline cellulose is sifted through suitable mesh sieve and the sifted mass is blended using high shear mixture and the blended mass is granulated with aqueous polyvinyl pyrrolidone solution and the granulated mass is dried until the moisture content comes down to less than 4% w/w and the dried mass is passed through suitable mesh sieve and this granules are lubricated with magnesium stearate, colloidal silicon dioxide and talc and the lubricated granules are compressed into mini-tablets.
These mini-tablets are coated with functional coating of ethyl cellulose and plasdone S 630 copolyvidonum. The diameter of film-coated mini-tablet ranges between 3 - 6 mm. These mini-tablets are then filled into hard gelatin capsule.
Such 12, 6, 3 mini-tablets are filled into pharmaceutically acceptable capsule to form 150 mg, 75 mg and 37.5mg strengths respectively of venlafaxine.
Dissolution Method
For all examples, the capsule containing tablets were tested for venlafaxine hydrochloride in 900ml of water. The tablets were placed in 40-mesh basket (USP Type 1) and rotated at 1OOrpm.
In the following examples, the composition and its dissolution profiles are given in a tabular form.

EXAMPLE 1
Composition

Ingredient Weight (mg/tablet)
Venlafaxine HCI 14.27
Microcrystalline Cellulose 7.13
Povidone 1.10
Ethyl Alcohol q.s
Talc 0.25
Colloidal Silicon Dioxide 0.25
Magnesium Stearate 0.50
Ethyl Cellulose 1.22
Copolyvidone 0.37
Ethyl Alcohol q.s.
Total Weight 25.09
Dissolution Profile

Time (hour) Percent Venlafaxine HCI released
1 0
2 13
4 38
8 62
12 75
24 92

EXAMPLE 2
Composition
Dissolution Profile

1 Ingredient Weight (mg/tablet)
Venlafaxine HCI 14.27
Microcrystalline cellulose 7.13
Povidone 1.10
Pure Water q.s.
Talc 0.25
Colloidal Silicon Dioxide 0.25
Magnesium Stearate 0.50
Ethyl Cellulose 1.59
Copolyvidone 0.48
Ethyl Alcohol q.s.
Total Weight 25.57

Time (hour) Percent Venlafaxine HCI released
1 0.2
2 7.7
4 23.2
8 46.2
12 60
24 81.9

EXAMPLE 3
Composition
Dissolution Profile

Ingredient Weight (mg/tablet)
Venlafaxine HCI 14.27
Microcrystalline cellulose 7.13
Povidone 1.10
Pure Water q.s.
Talc 0.25
Colloidal Silicon Dioxide 0.25
Magnesium Stearate 0.50
Ethyl Cellulose 1.08
Copolyvidone 0.32
Ethyl Alcohol q.s.
Total Weight 24.9

Time (hour) Percent Venlafaxine HCI released
1 6.2
2 22.7
4 48.8
8 77.5
12 92.2
24 102.7

EXAMPLE 4 Composition

Ingredient Weight (mg/tablet)
Venlafaxine HCI 14.27
Microcrystalline cellulose 7.13
Povidone 1.10
Pure Water q.s.
Talc 0.25
Colloidal Silicon Dioxide 0.25
Magnesium Stearate 0.50
Eudragit RS 30D 3.15
Talc 0.16
Triethyl Citrate 0.19
Pure Water q.s.
Total Weight 25.57
Dissolution Profile

Time (hour) Percent Venlafaxine HCI released
1 8
2 9
4 12
8 85
12 104
24 —
Further, when the composition of the present invention was extruded, spheronized and dried to form spheroids instead of mini-tablets as envisaged in the present invention, the dissolution profile was more immediate, which is unsuitable for once daily administration, as shown in the accompanying example:

Example 5
Composition:

Sr. No. Ingredient Qty/Capsul e(150gm)
CORE
1 Venlafaxine HCI 171.24
2 Microcrystalline Cellulose 85.56
3 Povidone 13.20
4 Water q.s.
COAT 270.00
8 Ethyl Cellulose 19.500
9 Copolyvidone 5.86
10 Ethyl Alcohol q.s.
TOTAL WEIGHT 295.36
A uniformly blended mixture of Venlafaxine Hydrochloride (171.24 g) and Microcrystalline cellulose (85.56 g) is granulated into an over wetted dough using solution of povidone (13.2 g) in water. The plastic mass was extruded, spheronized and dried to prepare uncoated spheroids. The cylindrical extrudes of the composition were very sticky and fragile with variable length of the extruded cylinders which resulted into non uniform spheroids during spheronization. The extrudes were difficult to spheronize. The formed spheroids were irregular shaped and excessively sticky in nature which resulted in the formation of aggregates. Aggregates were removed by sieving after drying the spheroids. The spheroids were further coated in a wurster type fluid bed coater with a solution of 19.5 g of Ethyl cellulose and 5.86 g of Copolyvidone in Ethyl alcohol. The fragile nature of the spheroids resulted in formation of too many fines while coating. The presence of fine bridged the formation of few aggregates during coating. The film coated spheroids were sieved to remove those aggregates and then filled into pharmaceutically acceptable capsules.
The in vitro drug dissolution studies were conducted on the formed spheroids using USP I at 37°C and 100 rpm in 900 ml water. The drug release is as follows,

Time (Hours) Percent
Venlafaxine HCI released
1 21
2 84
4 99
These suggests that preparing spheroids of the composition claimed in the present invention will have a drug release characteristics very different from the one desired for once a day administration, as also claimed in U.S. patent 6,274,171. The said invention is only workable for tablets of diameter greater than 3 mm and not for spheroids of diameter less than 2 mm.
Biopharmaceutics:
A randomized, two treatment, two period, two sequence, single dose, crossover bioavailability study on Venlafaxine 150 mg extended release capsule (Example 1), compared with Venlafaxine hydrochloride 150mg extended release capsule (Effexor XR™) manufactured by Wyeth Ayerst laboratories, USA, in 12 healthy, adult, male, human subjects was conducted under fasting conditions. The drug plasma level are shown in Figure 1. The Cmax values observed are 170.2 and 186.3 ng/ml for Effexor XR and Example 1, respectively. Whereas the AUC0-inf was 3306 and 4227 ng.h/ml for Effexor XR and Example 1, respectively.

WE CLAIM:
1. An extended release formulation of venlafaxine hydrochloride mini-tablets in a capsule comprising from about 40% to about 80% of venlafaxine hydrochloride by weight, from about 25% to about 45% of microcrystalline cellulose by weight and from about 0.5% to about 10% of polyvinyl pyrrolidine by weight of mini-tablet and the said mini-tablet are coated with from about 2% to about 15% of the weight of mini tablet and said coating comprised of from about 50% to about 95% by weight of water insoluble polymer and from about 3% to about 50% by weight of water soluble component.
' 2. An extended release formulation of venlafaxine hydrochloride according to claim 1, comprising of from about 48% to about 68% of venlafaxine hydrochloride by weight, from about 26% to about 38% of microcrystalline cellulose by weight and from about 2% to about 9% of polyvinyl pyrrolidine by weight of mini-tablet and the said mini-tablet are coated with from about 5% to about 14% of the weight of mini tablet and said coating comprised of from about 65% to about 95% by weight of water insoluble polymer and from about 5% to about 40% by weight of water soluble component.
3. An extended release formulation of venlafaxine hydrochloride according to claim 2, comprising of from about 57% to about 62% of venlafaxine hydrochloride by weight, from about 27% to about 32% of microcrystalline cellulose by weight and from about 2.5% to about 5.5% of polyvinyl pyrrolidine by weight of mini-tablet and the said mini-tablet are coated with from about 6% to about 12% of the weight of mini tablet and said coating comprised of from about 70% to about 80% by weight of water insoluble polymer and from about 20% to about 30% by weight of water soluble component.
4. An extended release formulation of venlafaxine hydrochloride according to claim 1, wherein the water insoluble polymer used are ethyl cellulose and eudragit.
5. An extended release formulation of venlafaxine hydrochloride according to claim 4, wherein water insoluble polymer used is ethyl cellulose.
6. An extended release formulation of venlafaxine hydrochloride according to claim 1, wherein the water soluble component used is copolyvidonium.

7. An extended release formulation of venlafaxine hydrochloride according to claim 1, 2 and 3, wherein diameter of mini-tablet ranges between 3 to 6 mm.
8. An extended release formulation of venlafaxine hydrochloride according to preceeding claims is given once daily.
9. A process for preparation of extended release formulation comprising of
i. Blending the venlafaxine hydrochloride and diluent.
ii. Granulating the blended mixture with an aqueous and non-aqueous
solution of binder and drying it.
iii. Lubricating the dried granules and compressing into tablets, iv. Coating the tablets with an aqueous or non-aqueous dispersion of
water insoluble and water soluble component, v. Filling coated mini tablets obtained in step (iv) into capsule of appropriate size.
Dated this 7th day of September 2005
Dr. Sanchita Ganguli Of S. MAJUMDAR & CO. Applicants' Agent