FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2006
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
" DUAL RETARD FORMULATION "
2. APPLICANT(S)
(a) NAME : TITAN LABORATORIES PVT. LTD.
(a) NATIONALITY : Indian (An Indian company incorporated under the
Companies Act 1956)
(b) ADDRESS : 102 TITAN HOUSE ,
M.P.VAIDYA MARG, 60 FEET ROAD,
GHATKOPAR -EAST,
MUMBAI - 400 077,
MAHARASHTRA,
INDIA.
3. PREAMBLE TO THE DESCRITION
COMPLETE
The following specification particularly describes the invention.

Field of Invention:
The current invention is in field of Galantamine Hydrobromide formulations. More specifically, the invention relates to Galantamine Hydrobromide dual retard formulations. In particular the invention relates to Galantamine extended release core /pellets / particles /beads and the like and the process thereof wherein the release is extended by the Dual retard technique and which comprise of the Galantamine Hydrobromide Glyceryl behenate Complex devoid of any excipients obtained by the hot melt process.
Background of Invention:
Galantamine is tertiary alkaloid which has been extracted from various plants from plants generally known as "snowdrops", like, Galanthus woronowi (Caucasian snowdrop or Galanthus nivalis (common snowdrop) and various species of Narcissus (daffodil), Leucojum (snowflake), and Lycoris including Lycoris radiata.
Since its extraction, Galantamine has been prescribed for various memory related disorders, including Alzheimer's disease/dementia as well as vascular dementia. Galantamine is used also used as a sleep aid.
Chemically Galantamine is a benzofuranol derivative having following structural formula:


The IUPAC name ascribed to above chemical structure is 4a,5,9,10,ll,12-
hexahydro-3-methoxy-ll-methyl-(4aS,6R,8aS)-6H-Benzofuro(3a,3,2-ef)(2)
benzazepin-6-ol.
Galantamine is generally prescribed as a thrice a day formulation owing to it half-life of about 7 hours. Consuming medications is not customary for any human being, taking a tablet after every eight hours to maintain the required pharmaceutical level, leads to reduced patient compliance. The fluctuations drug levels could invite under or over dosing. An alternative, for improving patient compliance, is to administer the drug in twice a day or once a day prolonged-release formulation. Thoughtful of this rationale many inventors have devised numerous sustained /extended /controlled release formulations of Galantamine.
WO 00/38686 (JANSSEN PHARMACEUTICA NV [BE]) claims a controlled release formulation containing galantamine as the active ingredient, characterized in that it comprises particles comprising galantamine or a pharmaceutically acceptable acid addition salt thereof, a water soluble pharmaceutically acceptable excipient and optionally other pharmaceutically

acceptable excipients, said particles being coated by a release rate controlling membrane coating. The formulation refers particularly to particles of galantamine along with excipients where the controlled release property is attributed by the virtue of the release rate controlling membrane coating.
The granted Indian Patent IN209167 of Janssen Pharmaceutica NV discloses a controlled release particulate formulation of galantamine. The controlled release formulation as disclosed in IN209167 comprises of an inert core. Said inert core is then overcoated with a layer comprising of the active mixed with a water soluble polymer which is then over-layered onto the inert core. The coated cores are, optionally, further coated with a seal coat. A release controlling coat is finally coated over the core thereby achieving SR profile.
US7160559B1 (Janssen) claims controlled release formulation containing galantamine as the active ingredient, characterized in that it comprises particles comprising galantamine Hydrobromide (1:1), and a water soluble film forming polymer wherein the galantamine Hydrobromide (1:1) and the water soluble film forming polymer are layered or coated on inert spheres, said particles being coated by a release rate controlling membrane coating wherein the release rate controlling membrane coating comprises a water insoluble polymer and optionally a plasticizer, and wherein the formulation further comprises a topcoat comprising galantamine and water-soluble polymer and wherein the formulation is capable of releasing in USP buffer pH 6.8 at 37[deg.] C. in a paddle apparatus operating at 50

rpm, from 20 to 40% of the total amount of Galantamine HBr in 1 hour, and more than 80% of the total amount of Galantamine HBr in 10 hours.
A dual retard technology was disclosed in Indian granted Patent Application No.
696/MUM/2002 and WO2004/012699. The specific advantage provided by this
dual retard technique formulation is to effectively reduce the quantity of release
controlling agents.
Further the small size makes the dosage form, makes it patient compliant for patients having difficulty in swallowing due to some medical condition. The application also claims a process for preparing the formulation. The dual retard technology used in this application is specifically for high solubility active ingredients.
The US7976871 specifically relates to a process for preparation of modified release dosage form comprising Metformin hydrochloride which involves a dual retard technology. The dual retard technique is a combination of a matrix formulation and a reservoir formulation.
Further the prior art refer to an Indian application 946/MUM/2008 which relates to extended release solid dosage forms of acetylcholinesterase inhibitors. In particular the present invention relates to extended release matrix solid dosage forms of galantamine.

Controlled release and Modified release formulations of Galantamine have been further disclosed in many PCT and US applications.
US2004/0097484 discloses once a day galantamine pharmaceutical compositions and methods of use. The composition provides release of at least about 5% of the galantamine or pharmaceutical^/ acceptable salt thereof after about 2 hours, at least about 25% of the galantamine or salt thereof in about six hours and at least about 50% of the galantamine or salt thereof in about ten hours, as measured in USP buffer pH 6.8 at 37[deg.] C. using USP Dissolution Apparatus 2 at 50 rpm.
US2005/0191349 describe Galantamine formulations, including sustained-release and fast dissolve formulations wherein the sustained release formulation exhibits a dissolution profile such that less than about 18% of the galantamine is released in 1 hour, and less than about 80% of the galantamine is released in 10 hours after combining the formulation with a dissolution medium at 37[deg.] C. in Apparatus 2 (USP, 711 Dissolution, paddle, 50 rpm).
WO2005/048979 (Torrent Pharmaceuticals Limited) claims a modified release pharmaceutical composition consisting of casing comprising at least two micro tablets, which are coated with rate controlling agent (s) optionally in combination with auxiliary pharmaceutical excipient (s), wherein each micro tablet comprises core particles comprising pharmaceutical active ingredient and rate controlling agent (s), the said core particles optionally coated with rate controlling agent (s),

wherein the ratio of pharmaceutical active ingredient to total rate controlling agent (s) ranges between 1 : 0.1 to 1 : 100 of each micro tablet. It further claims a process for preparation of the claimed modified release pharmaceutical composition.
WO2005/099674 claims controlled or sustained release solid pharmaceutical composition wherein the active agent is gabapentin, galantamine, topiramate, oxycodone, oxymorphone, hydromorphone or methylphenidate and composition comprises the claimed controlled or sustained release solid pharmaceutical excipient, comprising a release controlling excipient comprising an amphiphilic starch.
WO2007/121537 (Alphapharm PTY Ltd [AU]) relates to controlled release formulations comprising uncoated discrete unit(s) and an extended release matrix.
US2007/0092568 relates to controlled release compositions of galantamine, processes to prepare the compositions where the composition comprise a portion of the contained galantamine in an immediate release form and another portion in an extended release form.

WO2007/029081 relates to Galantamine containing controlled release oral dosage forms, processes for the preparation thereof and use for the manufacture of a medicament
WO2008/048469 describes controlled-release galantamine formulations, including controlled-release particles, pellets, granules, and spheres. Controlled-release particles, pellets, granules, and spheres with immediate release top-coat are also described. Method of preparing such formulations and method of treating a variety of disorders are also disclosed wherein the formulation exhibits a dissolution profile such that at 1 hour about 4 to about 9% of the galantamine is released, at 2 hours about 15 to about 25% of the galantamine is released, at 4 hours about 40 to about 55% of the galantamine is released, and at 8 hours about 80 to about 100% of the galantamine is released after combining the dosage formulation with 900 ml of pH 6.5 phosphate buffer at 37°C in USP Type 1 Apparatus (USP5 < 711> Dissolution), at a paddle speed of 100 rpm.
WO2008/062426 (Emcure Pharmaceuticals Ltd.) discloses a unit dosage pharmaceutical preparation. The said preparation comprises: a. functional coated composition of galantamine or its salts; and b. uncoated/seal coated composition of galantamine or its salts.
WO2008/064734 this invention relates to a controlled release medicament of galantamine comprising a pellet having an inert core, layered with two coating

layers such that the first coating and the second coating contain the active substance galantamine or a pharmaceutically acceptable salt or solvent thereof, and the composition of the first coating is different from the composition of the second coating and at least one of the coatings comprises a film-forming, water insoluble polymer.
946/MUM/2008 of Alembic Limited discloses and claims an extended release
matrix solid dosage form comprising galantamine.
Further, an extended-release formulation of galantamine is also disclosed in 1753/CHE/2008 of Aurobindo Pharma Ltd. The said application relates to a pellet or particulate formulation of Galantamine particularly to extended release dosage forms of Galantamine Hydrobromide and the process for preparing the same. The . dosage forms comprises of an inert core coated with the active layer and is free of excipients and further coated with a second layer comprising release rate controlling polymer and excipients and a final immediate release drug layer which is free of excipients.
A core coat sustained release formulation of Galantamine was disclosed in 1248/DELNP/2008 (Ranbaxy Laboratories Ltd.)
WO2009/024858 (Aurobindo Pharma Ltd.) claims a controlled release dosage form comprising a matrix core comprising galantamine or its salts, release retarding polymer and one or more pharmaceutically acceptable excipients and an

immediate release drug layer over the core comprising galantamine or its salts and one or more pharmaceutically acceptable excipients.
WO2011/064797 (USV Ltd.) relates to Controlled release pharmaceutical compositions of galantamine. The compositions disclosed and claimed herein comprise a plurality of matrix mini tablets comprising Galantamine or its pharmaceutically acceptable salt and at least one release modifying agent. Said compositions are characterized by the absence of release rate modifying coating and/or absence of an immediate release portion of the Galantamine.
Dual retard technique has been patented for several active pharmaceutical ingredients. The one disclosed and claimed in WO 2004/012699 A2 and 696/MUM/2002 is for high solubility active ingredient.
The process specific to Metformin Hydrochloride is claimed in US7976871 involving micro matrix particles and further a control release coating. The matrix as claimed comprises of acrylate polymers and further coat which consists of release controlling agents from the category of waxes, fatty alcohols and fatty acid esters.
The technique has also been claimed in WO 2004/012700 A2 which claims dosage form of combination of high dose high solubility active ingredient, as modified release and low dose active ingredient as immediate release suitable for

swallowing; comprising of dual retard technique to control the release of high dose, high solubility active ingredient.
Considering the current conventional dosing of Galantamine of twice or thrice a day and to encourage patient compliance and avoid drug level fluctuations and in light of the prior art specifically with reference to technologies that relate to the dual retard technique the inventors hereby propose a robust and novel dual retard release formulation of galantamine. The compositions would also exhibit constant plasma levels of galantamine maintained over an extended period of time.
The dual retard techniques referred to in prior art do not refer to dual retard technology for sparingly soluble actives also it does not claim or disclose use of fatty acid esters or lipids in matrix for controlled release . The process as claimed or disclosed in prior art also do not refer to the Complex formation of Drug and lipid (Glyceryl behenate) by hot melt process and further the complex thus formed being further subjected to the extrusion spheronization .The pellets thus formed are further coated with an extended release rate controlling polymer.
Glyceryl dibehenate; is a mixture of glycerol esters. The Ph.Eur. 6.0 describe glyceryl dibehenate as a mixture of diacylglycerols, mainly dibehenoylglycerol, together with variable quantities of mono- and triacylglycerols. Glyceryl behenate is investigated for use in the preparation of sustained-release tablets; as a matrix-

forming agent for the controlled release of water-soluble drugs; and it can also be used as a hot-melt coating agent sprayed onto a powder or drug-loaded sugar beads and granules. It may also be incorporated via extrusion/spheronization into pellets, which can be further compressed into tablets. [Handbook of Pharmaceutical excipients 6 edition Published by the Pharmaceutical Press Pages 286 -287].
The formulation referred to in this invention particularly relate to Galantamine Hydrobromide extended release cores/ pellets / particles /beads and the like wherein the release is extended by the Dual retard technique and which comprise of the Galantamine Hydrobromide Glyceryl behenate Complex devoid of any excipients obtained by the hot melt process.
The dual retard technique referred to above in the formulation is contributed by Complex and secondly the retard coat over the matrix pellets.
The matrix extended release pellets are obtained by the extrusion spheronization process of the Glyceryl behenate and Galantamine Hydrobromide complex formed initially by hot melt granulation. The hot melt process does not involve any other solvents or excipients soluble or insoluble other than Glyceryl behenate and Galantamine Hydrobromide during the complex formation.

The complex of Glyceryl behenate and Galantamine Hydrobromide formed by hot melt process institutes the novelty and robustness of the formulation. The formulation is further processed by the conventional extrusion granulation process known in art after granulating the thus formed complex with a suitable binder and further processed to form the cores/particles/pellets/ beads and the like. The final cores are coated with an extended release coat to exhibit the dual retard.
Detailed Description of Invention:
Galantamine Hydrobromide is sparingly soluble in water; insoluble chloroform, ether and alcohol. Galantamine is primarily metabolized in the liver via the cytochrome P450 (CYP) pathway. In vitro studies indicate that CYP3A4 and 2D6 are the major isozymes involved in galantamine metabolism. CYP3A4 mediates the formation of galantamine-N-oxide, and CYP2D6 mediates the formation of odemethyl- galantamine. However, the inhibitory effect of galantamine metabolites is not considered to be clinically relevant.
Galantamine has a large volume of distribution (~ 175 L) following oral administration. The plasma protein binding is 18% at therapeutically relevant concentrations. [Drug Profile - Galantamine for Alzheimer's Disease Ophelia QP Yin, PhD; Moses SS Chow, PharmD, Medical Progress February 2002]
Glyceryl behenate is a high melting point lipid used in modified release oral solid dosage forms. It can be used in solvent free complexation or granulation techniques to achieve the extended release effect.

Particles/ Pellets/beads are increasingly being used as multiple unit dosage forms. Pellets possess many pharmacological advantages as they disperse freely in the gastrointestinal tract, maximize drug absorption, reduce peak plasma fluctuations and minimize potential side effects with or without appreciably lowering the bioavailability [Elchidana, P.A.; Deshpande, S.G. J. Control. Rel. 1999, 59, 279-285]. They avoid high local concentrations of bioactive agents, which may inherently be irritative or anesthetic to stomach [Fekete, R.; Zelko, R.; Marton, S.; Racz, I. Drug Dev. Ind. Pharm.1998, 24, 1073-1076]. Additionally they reduce intra and inter subject variability of plasma profiles by reducing variations in gastric emptying rates and overall transit times.
Core refers to the center portion of coated dosage unit. The core portion comprises the complexed active agent, either with or without added excipients.
The terms 'cores' or 'pellets' or 'particles' or 'beads' or the like are synonymous and used interchangeably herein and refer to the inner portion of the formulation comprising the Galantamine Hydrobromide -Glyceryl Behenate complex along with the excipients . These cores being finally coated with the extended release polymer coat.

Excipients referred here to in the invention may comprise of one or more binding agents, diluents, lubricants, disintegrants, suspending agents sustaining agents, colorants and other excipients known in art.
The sustaining or controlled or extended effect can be achieved by a dual retard technique which involves the matrix system comprising the Active ingredient and lipid complex formed by the hot melt process incorporated into the extrudates cores /pellets/particles /beads and whereby further retard is imparted to the drug loaded extended release matrix cores /pellets/particles /beads by coating the drug loaded extended release matrix cores/pellets/particles /beads by a water insoluble cellulosic polymer to achieve the desired profile.
The object is achieved in particular by active matrix cores /pellets /particles /beads comprising the Galantamine Glyceryl behenate complex obtained by the hot melt process which if further subjected to extrusion spheronization process to meet the desired goal.
The further objective of obtaining extended release / sustained release /controlled release of Galantamine matrix pellets /particles / beads by the dual retard technique is further achieved by further coating them with sustained release polymer to give the desired drug release.

The invention furthermore relates to a process for the production of the particles /
pellets.
In an embodiment, the process of the invention involves the following steps:
Manufacturing Process in brief:
Matrix Drug pellets preparation and coating:
1. Weighing all the ingredients accurately.
2. Melting Glyceryl Behenate at 70°C.
3. Granulating Galantamine Hydrobromide with the melted Glyceryl Behenate at 70°C to obtain the Galantamine Glyceryl behenate complex.
4. After granulation mixing the complex continuously till it cools to room temperature.
5. Sizing the Galantamine Glyceryl behenate complex obtained in step 4.

6. Sifting microcrystalline cellulose through specified SS sieve.
7. Sifting Magnesium Stearate through specified SS sieve.
8. Mixing together the excipients of step 6 and 7 along with the complex obtained in step 5 in a planetary mixer.
9. Preparing the binder solution comprising Povidone K 30 in Iso propyl alcohol.
10. Granulating the mix obtained in step 8 in Planetary Mixer using binder solution of step 9.
11. Subjecting the wet mass obtained in step 10 to extrusion and spheronization.

12. Sizing the pellets to obtain pellets within the desired size range.
13. Coating the sized pellets obtained in step 12 in Fluid Bed Coater with ER (extended release polymer) coating solution.
A further embodiment refers to extended release Galantamine Hydrobromide formulation comprising the Galantamine Hydrobromide Glyceryl Behenate complex further processed and coated with a water insoluble cellulosic polymer which is Ethyl Cellulose.
In an optional embodiment, the final coated particles or pellets or beads of Galantamine can be further filled in hard gelatin capsules or can be further formulated in the form of tablets, suspensions etc. as required.
Further embodiments relate to hard gelatin capsules specifically where the SR pellets of Galantamine are combined with immediate release pellets of Galantamine to yield a formulation exhibiting an immediate as well as retard release profile in the same formulation which could be referred to as a dual pellet system.
The above embodiments and process is emphasized below with examples to rule out the ambiguity if any and for clearer understanding of the invention and in no way meant to limit the scope of the invention.
The abovementioned embodiments and process is accentuated with below mentioned examples. These examples are illustrative and are not meant to limit the scope of the invention.

Examples:
Galantamine ER Pellets 8% w/w
Each l00mg of pellets contains:
Galantamine Hydrobromide eq. to Galantamine....8mg
Example 1: Detail of the batch on lab scale using laboratory apparatus and
equipment for preparing the Galantamine Glyceryl behenate complex and further
drug pellets preparation comprising the complex.
Table 1

Batch No. RD11
Uncoated Drug Pellets comprising Galantamine Glyceryl behenate complex
Ingredients %
Galantamine Hydrobromide 11.80
Glyceryl Behenate (Compritol 88 ATO) 53.00
Microcrystalline Cellulose PH 101 32.20
Magnesium Stearate 2.50
Povidone (PVP K 30) 0.50
Isopropyl Alcohol q.s.
Procedure: All the ingredients as mentioned in Table 1 were weighed accurately and sifted. Galantamine Hydrobromide was heated upto 70°C and granulated with molten Glyceryl Behenate which had been melted at the same temperature. The granulated mass was mixed till cool and sized through specified sieve. The sized

granules were mixed with Microcrystalline cellulose and Magnesium stearate to get a uniform blend.
Binder solution was prepared by dissolving PVP K 30 in Isopropyl Alcohol. The dry blend of the active along with the excipients as mentioned above was granulated with the PVP K 30 binder solution.
The wet mass was then extruded out using specified screen at the set speed. The extrudates were spheronized using chequered plates to get pellets between 16 -20# size. The sized pellets are dried to achieve an LOD of NMT 3.0% w/w.
The dried and sized pellets were subjected to dissolution to check the drug release in 6.8 pH Phosphate buffer.
Uncoated Drug Pellets comprising Galantamine Glyceryl behenate complex -Assay & Dissolution:
Dissolution parameters:
Dissolution Media and Volume: 6.8 pH Phosphate buffer 900 ml
Apparatus: USP Apparatus II (Paddle) Speed: 50 rpm
Table 2:

Assay 95.00 %
Dissolution (1 Hr pH 6.8) 59.20%
Dissolution (4 Hr pH 6.8) 82.60%

With a satisfactory dissolution result of the drug pellets in Phosphate buffer the pellets were further coated in Fluid Bed Coater with extended release coating dispersion as given in Table 3 below and further dried in Fluid Bed Processor to achieve LOD of NMT 3.0% w/w to exhibit dual retard such that the final dissolution results are achieved within the below set dissolution range in the stipulated time intervals.
Dissolution (lHr pH 6.8) (Limit: 10-40%)
Dissolution (4Hr pH 6.8) (Limit: 40-70%)
Dissolution (lOHr pH 6.8) (Limit: NLT 65%)
Dissolution (12Hr pH 6.8) (Limit: NLT 70%)
Table 3

B.No: RD11
ER coating formula to coat Drug Pellet Galantamine Glyceryl behenate complex s comprising
Ingredients %
Ethyl Cellulose lOcps 0.5
Dibutyl Phthalate 0.13
Isopropyl Alcohol q.s.
Dichloromethane q.s.

Procedure: Ethyl Cellulose was dissolved in Isopropyl Alcohol under stirring. Dichloromethane was added further to the ethyl cellulose dispersion followed by Dibutyl phthalate under continuous stirring to get a uniform dispersion.
The uncoated drug pellets of Table 1 were loaded in the Fluid Bed Coater and coated with the extended release coating dispersion of Table 3.
The final extended release coated pellets of Galantamine Hydrobromide were subjected to Dissolution studies in three media and water and compared with a dissolution study of the innovator product Razadyne.
The three dissolution media which had been selected for the dissolution study were as follows:
1. 0.1 N Hydrochloric acid 2. pH 4.5 Acetate buffer 3. pH 6.8 phosphate buffer
Dissolution Parameters:
Dissolution Media and Volume: 900 ml
Apparatus: USP Apparatus II (Paddle) Speed: 50 rpm
The comparative dissolution studies have been tabulated below in Tables 4 -7:
Galantamine Hydrobromide Extended Release Capsules Table 4: Dissolution media : Water

Batch No. Dissolution lHr 4Hr 10 Hr 12 Hr Fl F2
LAG467(Razadyne) Water 27.5 57.9 81.8 85.1 10.08 57.69
RD031A-02/12 Water 30.8 53.5 89.1 95.5

Table 5: Dissolution media : 0.1N Hydrochloric acid

Batch No. Dissolution lHr 4Hr 10 Hr 12 Hr Fl F2
LAG467(Razadyne) 0.1NHC1 27.8 56.2 81.2 85.4 12.62 52.77
RD031A-02/12 0.1NHC1 34.7 53.4 88.5 94.8

Table 6: Dissolution media : pH 4.5 Acetate buffer

Batch No. Dissolution lHr 4Hr 10 Hr 12 Hr Fl F2
LAG467(Razadyne) pH 4.5 buffer 27.6 56.8 81.3 84.4 12.93 51.93
RD031A-02/12 pH 4.5 buffer 34.4 54.6 91.1 97.8

Table 7: Dissolution media : pH 6.8 Phosphate buffer

Batch No. Dissolution lHr 4Hr 10 Hr 12 Hr Fl F2
LAG467(Razadyne) pH 6.8
phosphate
buffer 26.4 55.8 79.5 83.3 16.04 47.94
RD031A-02/12 pH 6.8
phosphate
buffer 38.0 58.3 92.1 97.3

The above lab scale optimized formulation was standardized on a Hot Melt Extruder.

Example 2: Detail of the batch usine Hot Melt Extrusion technique for preparation of Galantamine Hydrbromide Glyceryl behenate complex and further drug pellets preparation comprising the complex
Table 8

B.No: RD12
Uncoated Drug Pellets formula comprising Glyceryl behenate complex Galantamine
Ingredients %
Galantamine Hydrobromide 11.00
Glyceryl Behenate (Compritol 88 ATO) 52.00
MCCPH101 34.00
Magnesium Stearate 2.50
Povidone (PVP K 30) 0.50
Isopropyl Alcohol q.s.
Galantamine Hydrobromide -Glyceryl Behenate Complex was prepared in a Hot Melt Extruder.
Melting point and Temperature details:
Melting point of Galantamine Hydrobromide: 262°C - 270°C Melting point of Glyceryl Behenate: 69°C - 74°C Hot melt extrusion carried out at 75°C - 80°C

Galantamine Hydrobromide and Glyceryl behenate was blended and introduced into hot melt extruder. The process of complexation was carried out and maintained at 70°C .The churning mechanism of the screws initiated the granulation process .The granulated mass was then forced through the extruder die which resulted in particle formation. These particles were cooled to room temperature and further processed.
Further steps of peptization and coating of the pellets with ER coat were in congruence with the procedure as depicted in Example 1.
Sustained release coating solution for coating the drug pellets was in compliance with the formula as given in Table 9.
Table 9:

SR coating formula: RD12
%
Ethyl Cellulose 10 cps 0.5
Dibutyl Phthalate 0.13
Isopropyl Alcohol q.s.
Dichloromethane q.s.
The above ER coated pellets were subjected to Assay and Dissolution studies. The results are as tabulated below in Table 10.

Table 10: Assay and Dissolution

Assay and Dissolution Drug Pellets comprising complex SR coated pellets
Assay 97.50 104.6
Dissolution (1 Hr pH 6.8) 38.40 17.6
Dissolution (4 Hr pH 6.8) 80.00 59.5
Dissolution (10 Hr pH 6.8) 92.80 99.1
Dissolution (12 Hr pH 6.8) 92.40 99.8
Various modifications of aforementioned embodiments and examples are readily apparent to a person skilled in the art. All such modifications may be construed to fall within the scope and limit of this invention as defined by the appended claims.
We claim
1. An extended release formulation of Galantamine utilizing dual retard technique and comprising a coated core, wherein the core comprises a Galantamine Hydrobromide -Lipid complex
2. An extended release formulation of Galantamine as claimed in claim 1 wherein Galantamine Hydrobromide -Lipid complex is prepared by the hot melt technique.

3. An extended release formulation of Galantamine as claimed in preceding claims wherein the lipid is Glyceryl behenate.
4. An extended release formulation of Galantamine as claimed in preceding claims wherein the core is coated with a water insoluble cellulosic polymer.
5. An extended release formulation of Galantamine as claimed in preceding claims wherein the water insoluble cellulosic polymer is Ethyl Cellulose.
6. A process of preparing an extended release formulation of Galantamine utilizing dual retard technique and comprising a coated core, wherein the core comprises a Galantamine Hydrobromide -Lipid complex
7. A process of preparing an extended release formulation of Galantamine claimed in claim 6 and comprising the steps of:
i. Preparing the Galantamine Hydrobromide -lipid complex
ii. Granulating the complex with pharmaceutically acceptable
excipients to form the core /pellets /particles /beads. iii. Coating the cores formed in step iii with a water insoluble cellulosic
polymer.
8. A process of preparing an extended release formulation of Galantamine as
claimed in claim 6, 7 wherein the lipid is Glyceryl behenate.

9. A process of preparing an extended release formulation of Galantamine as claimed in claim 6, 7 and 8 wherein the water insoluble cellulosic polymer is Ethyl Cellulose.
10. An extended release formulation of Galantamine utilizing dual retard technique and comprising a coated core, wherein the core comprises a Galantamine Hydrobromide -Lipid complex and exhibits the following dissolution profile when measured in a type II dissolution apparatus according to the U.S. Pharmacopoeia in 6.8 pH phosphate buffer at 37°C, wherein 10% to 40% of Galantamine Hydrobromide is released in 1 hour , 40% to 70% of Galantamine Hydrobromide is released in 4 hours , not less than 65% of Galantamine Hydrobromide is released in 10 hours and not less than 70% of Galantamine Hydrobromide is released in 12 hours