FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patent Rules, 2003
COMPLETE SPECIFICATION
[Section 10, and Rule 13]
CONTROLLED RELEASE PHARMACEUTICAL COMPOSITIONS OF TOLTERODINE AND PROCESS FOR PREPARATION THEREOF
Applicant
Name: Torrent Pharmaceuticals Limited
Nationality: Indian
Address: Torrent House, Off Ashram Road, Near Dinesh
Hall, Ahmedabad 380 009, Gujarat, India
The following specification particularly describes the nature of the invention and the manner in which it is to be performed:

FIELD OF THE INVENTION
The invention relates to controlled release pharmaceutical compositions of tolterodine, and process for preparing such compositions.
BACKGROUND OF THE INVENTION
A substantial part of the adult population suffers from overactive or unstable urinary bladder, often also referred to as urinary incontinence. The symptoms of an unstable or overactive bladder include urge incontinence, urgency and urinary frequency. The prevalence of overactive bladder, particularly urge incontinence, increases with age. It is assumed that unstable or overactive bladder is caused by uncontrolled contractions of the bundles of smooth muscle fibres forming the muscular coat of the urinary bladder (the detrusor muscle) during the filling phase of the bladder. These contractions are mainly controlled by cholinergic muscarinic receptors, and the pharmacological treatment of unstable or overactive bladder has been based on muscarinic receptor antagonists.
Tolterodine, chemically known as (R)-N, N diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropanamine, is a well known muscarinic receptor antagonist specifically developed for treatment of patients with overactive bladder. The synthesis of tolterodine and its utility for the treatment of overactive bladder is disclosed in US Patent No. 5,382,600. Known administration forms of tolterodine are, for example, film-coated tablets containing 1 mg or 2 mg of tolterodine L-tartrate for immediate release in the gastrointestinal tract. An optimal efficacy/side effect profile is obtained at an oral dosage of 1 or 2 mg twice daily. The oral administration of tolterodine results in its metabolization in the liver, resulting in the formation of its 5-hydroxymethyl derivative, which is a major pharmacologically active metabolite. The 5-hydroxymethyl metabolite exhibits an anti-muscarinic activity similar to that of tolterodine, which contributes significantly the therapeutic effect.
The immediate release administration forms of tolterodine are however thought to be associated with side- effects, such as "dry mouth". It is known that administration

forms capable of controlling drug release provide a significant advantage in terms of increased patient compliance, improved delivery efficiency, decreased total drug requirement, minimization or elimination of local or systemic side effects, and minimization of drug accumulation with chronic dosing. In general, the most important therapeutic advantage of a controlled release dosage form is that the blood level of the drug can be maintained for long time with minimal fluctuation. Tolterodine tartrate is also commercially marketed as extended release capsules by Pharmacia under the brand name DETROL® LA. The capsules contain either 2 or 4 mg of tolterodine tartarate.
Several approaches for preparing controlled release compositions of tolterodine are disclosed in the art. For example, the WO 00/27364 patent application assigned to Pharmacia & Upjohn discloses controlled release beads comprising: (i) a core unit of water-soluble or water-insoluble polymer; (ii) a first layer on the core unit of a substantially water-insoluble polymer;(iii) a second layer covering the first layer and containing the active ingredient and (iii) a third layer on the second layer of polymer effective for controlled release of active ingredient. In these controlled release beads, the first layer is adapted to control water penetration into the core.
The WO 04/105735 patent application assigned to Ranbaxy Laboratories Ltd. discloses a controlled release pharmaceutical composition of tolterodine which includes one or more coated units. Each coated unit includes a core, a first layer, and a second layer. The first layer surrounds at (east a portion of the core and includes tolterodine and one or more hydrophilic polymers. The second layer surrounds at least a portion of the first layer and includes one or more polymers that are effective for controlled release of tolterodine from the first layer.
The WO 05/105036 patent application assigned to Natco Pharma Ltd. discloses a controlled release oral pharmaceutical mucoadhesive matrix formulation containing a therapeutically effective amount of tolterodine or its pharmaceutically acceptable salts, prodrugs and metabolites thereof dispersed in a rate controlling polymeric

matrix comprising (1) a pH independent gelling polymer, such as polyethylene oxide, (2) pH dependent gelling polymer, such as sodium of carboxymethylcellulose (3) film coating polymer component, such as Eudragit RS100 and other conventional tablet functional excipients. The formulation is in the form of tablet or mini-tablets in capsules and relates to a 24 hour controlled release dosage form useful for the treatment of urge incontinence.
The WO 06/21425 patent application assigned to KRKA discloses a sustained release pharmaceutical composition comprising an outer layer coated on the first layer or on the matrix core, which outer layer comprises a hydrophobic sustained release polymer and, at least one core element, which is selected from (i) an inert core, said inert core being provided with a first layer comprising tofferodine and a binder, and (ii) a matrix core formulation, said matrix core formulation being a combination of a matrix core material, tolterodine and a binder.
The WO 07/29087 patent application assigned to Ranbaxy Laboratories Ltd. discloses a controlled release multiple unit dosage form comprising: (i) an inert core unit comprising ethyl cellulose and optionally one or more water- soluble or water-swellable excipients; (ii) an active layer on the surface of the inert core comprising one or more active ingredients and one or more hydrophilic polymers; and (iit) polymeric layer over the active layer, wherein the polymeric layer is effective for controlling or modifying the release of active ingredient.
The WO 07/46590 patent application assigned to GL Pharmtech Corp. discloses a sustained-release multiple unit dosage form comprising: 1) hydrophobic multiple unit cores comprising at least one selected from the group consisting of a wax, a higher fatty acid and a glyceryl fatty acid; 2) a drug-containing layer coated on the surface of said core; and 3) a controlled-release membrane coated on the surface of said layer.
The WO 07/00778 patent application assigned to Panacea Biotec Ltd. discloses a modified release pharmaceutical composition comprising at least one active agent (s) or its pharmaceutically acceptable salts, esters, prodrugs, solvates, hydrates, or

derivatives thereof; a polymer system in an amount less than about 80% w/w of the composition comprising at least two swellable pH independent polymers wherein at least one is hydrophilic; optionally other pharmaceutically acceptable excipients; wherein the composition provides therapeutic concentrations of active agent(s) for extended periods of time.
There remains a need in the art for alternative pharmaceutical compositions of tolterodine which provides therapeutic concentrations of tolterodine for extended period of time.
SUMMARY OF THE INVENTION
One embodiment provides a controlled release pharmaceutical composition comprising one or more units, wherein the unit comprises: (i) an inert core;
(ii) a first coat coated on the core comprising tolterodine and a binder selected from the group consisting of saccharides, sugar alcohols, and mixtures thereof; and (iii) a second coat on the first coat comprising a release modifying polymer and one or more pharmaceutically acceptable excipients.
Another embodiment provides a controlled release pharmaceutical composition comprising one or more units, wherein the unit comprises: (i) a core comprising tolterodine;
(ii) a first coat coated on the core comprising tolterodine and a binder selected from the group consisting of saccharides, sugar alcohols, and mixtures thereof; and (iii) a second coat on the first coat comprising a release modifying polymer and one or more pharmaceutically acceptable excipients.

Another embodiment provides a controlled release pharmaceutical composition
comprising:
(i) a core comprising
a) tolterodine;
b) a release modifying polymer; and
(ii) a coating on the core comprising a release modifying polymer and one or more pharmaceutical^ acceptable excipients.
Yet another embodiment provides a controlled release pharmaceutical composition comprising:
(i) a core comprising
a) tolterodine;
b) hydroxypropyl methylcellulose comprising viscosity in the range of 1 cps to 100 cps; and
c) hydroxypropyl methylcellulose comprising viscosity in the range of 3000 cps to 6000 cps;
(ii) a coating on the core comprising a release modifying polymer and one or more pharmaceutically acceptable excipients.
Yet another embodiment provides a process for preparing a controlled release pharmaceutical composition, wherein the process comprises:
(a) providing an inert core;
(b) coating the inert core with tolterodine and a binder selected from the group consisting of saccharide, sugar alcohol, or mixtures thereof; and
(c) coating the drug-coated core of step (b) with one or more release modifying polymer and optionally one or more pharmaceutically acceptable excipients;
(d) optionally mixing the product of step (c) with one or more pharmaceutically acceptable excipients; and
(e) compressing the product of step (c) or (d) into a tablet or filling into a capsule to obtain the pharmaceutical composition.

DETAILED DESCRIPTION OF THE INVENTION
The term "tolterodine" as described herein encompasses the R-isomer, the S-isomer and the racemic mixture of tolterodine free base, as well as pharmaceutically acceptable salts, prodrugs, metabolites thereof, or enantiomers thereof. It also includes hydrates, solvates and polymorphs of tolterodine free base or pharmaceutically acceptabie salts thereof; or mixtures thereof. The preferred salt of tolterodine is tolterodine tartrate. Tolterodine may be present in an amount ranging from about 1 % to about 90 % by weight of the composition.
The release modifying polymer may be selected from a hydrophilic polymer, hydrophobic polymer, and the like. The hydrophilic polymer may be selected from the group consisting of gums such as acacia gum, tragacanth gum, locust bean gum, guar gum, karaya gum, pectin, carrageenan, soluble or insoluble alginates, and the like; polyethylene oxide, modified cellulose derivatives like methylcellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, and the like; carbomer, sodium carboxymethylcellulose, carboxypolymethylene, gelatin, zein, bentonite, and the like. The preferred hydrophilic polymer is hydroxypropyl methylcellulose (HPMC) which is available in various grades with viscosity ranging of 1 -1,00,000 cps. Particularly suitable are grades having viscosity ranging from, for example, 1-100 cps, or for example, ranging from 3000-6000 cps; or mixtures of such grades. The hydrophilic polymer may be present in an amount ranging from 5 % to 50 % by weight of the composition,
The hydrophobic polymer may be selected from polymethacrylates, polyacrylate, polyvinyl acetate, ethylcellulose, cellulose acetate, cellulose propionate, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, waxes such as beeswax, carnauba wax, microcrystalline wax, and the like; fatty alcohols such as cetostearyl alcohol, stearyl alcohol, cetyl alcohol, myristyl alcohol, and the like; and fatty acid esters such as glyceryl monostearate, glyceryl distearate, glycerol monooleate, acetylated monoglycerides, tristearin, tripalmitin, glyceryl palmitostearate, glyceryl behenate, hydrogenated castor oil, and the like.

The hydrophilic polymer may be present in an amount ranging from 1 % to 30 % by weight of the composition.
The core as described herein may include one or more of an inert core or core comprising the active ingredient i.e. tolterodine. The inert core may include one or more non-pareil seed made of microcrystalline cellulose or sugar spheres, such as those made of mannito!, lactose, dextrose, sucrose, and the like. The core may be present in an amount ranging from 50 % to 95 % by weight of the composition.
The pharmaceutical compositions as described herein may comprise one or more pharmaceutically acceptable excipients selected from binder, diluent, disintegrant, plasticizer, opacifier, glidant, lubricant or anti-adherent.
Binder as described herein may be selected from sachharide, sugar alcohol, cellulose derivatives, such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethylcellulose sodium, and the like; carbomers, shellac, zein, gelatin, polymethacrylates, polyvinyl pyrrolidone, pregelatinized starch, gums, synthetic resins and the like. Saccharide may be selected from glucose, fructose, lactose, sucrose, trehalose, and the like. Sugar alcohol may be selected from mannitol, erythritol, xylitol, maltitol, sorbitol, and the like. The diluent may be present in an amount ranging from 0.1 % to 20 % by weight of the composition.
Diluent as described herein may be selected from cellulose derivatives such as powdered cellulose, microcrystalline cellulose, silicified microcrystalline cellulose; starch, dibasic calcium phosphate, tribasic calcium phosphate, calcium carbonate; saccharides such as lactose, sucrose or dextrose; sugar alcohols such as mannitol, sorbitol or erythritol; or mixtures thereof. The diluent may be present in an amount ranging from 1 % to 90 % by weight of the composition.
Disintegrant as described herein may be selected from calcium carboxymethyl
cellulose, cross-linked carboxymethyl cellulose sodium, cross-linked

polyvinylpyrrolidone, carboxymethyl cellulose sodium, sodium starch glycolate, pregelatinized starch; low substituted hydroxy propyl cellulose; or mixtures thereof. The disintegrant may be present in an amount ranging from 1 % to 20 % by weight of the composition.
Plasticizers as described herein may be selected from acetyl tributyl citrate, acetyl triethyl citrate, acetylated fatty acid glycerides, castor oil, diethyl phthalate, diethyl sebacate, dibutyl sebacate, dimethyl phthalate, glycerol, glyceryl monostearate, glyceryl triacetate, polyoxyethylene/polyoxypropylene copolymers, polyethylene glycol, triethyl citrate, dibutyl phthalate, oils, and propylene glycol. The plasticizer may be present in an amount ranging from 1 % to 10 % by weight of the composition.
Opacifier may be selected from titanium dioxide, iron oxides, and the like. The opacifier may be present in an amount ranging from 0.1 % to 10 % by weight of the composition.
Lubricant, glidant or anti-adherent as described herein may be selected from talc, metallic stearates such as magnesium stearate, calcium stearate, zinc stearate; colloidal silicon dioxide, finely divided silicon dioxide, stearic acid, hydrogenated vegetable oil, glyceryl palmitostearate, glyceryl monostearate, glyceryl behenate, polyethylene glycols, powdered cellulose, starch, sodium stearyl fumarate, magnesium trisilicate, kaolin; or mixtures thereof. It would be appreciated that a person skilled in the art is cognizant of the fact that lubricant, glidant or anti-tacking agent may be used interchangeably. The lubricant, glidant or anti-adherent may be present in an amount ranging from 0.1 % to 20 % by weight of the composition.
The pharmaceutical compositions as described herein may be in the form of tablet, capsule, sachet, and the like. The compositions may be prepared by techniques such as wet granulation, dry granulation, drug layering, and the like. For example, tolterodine may be mixed with a release modifying polymer and optionally one or

more pharmaceutical^ acceptable excipients, and the mixture may be granulated with water or an organic solvent in a conventional apparatus, such as rapid mixer granulator or a fluid bed processor to form granules (core). Alternatively, the mixture of tolterodine, release modifying polymer and optionally one or more pharmaceutically acceptable excipients may be compacted in a roller compacter and the compacts may be milled to obtain granules (core). The granules may be coated with a solution or dispersion of release modifying polymer, one or more pharmaceutically acceptable excipients such as a binder, and optionally tolterodine. Alternatively, the granules may be compressed into a tablet (core) which may further be coated with a solution or dispersion of release modifying polymer, one or more pharmaceutically acceptable excipients, and optionally tolterodine. The tablet may be filled in capsules of suitable size to obtain the compositions. Alternatively, inert non-pariels (core) may be coated with a solution or dispersion of tolterodine and one or more pharmaceutically acceptable exctpients such as a binder to obtain drug-coated pellets which may further be coated with a solution or dispersion of release modifying polymer and one or more pharmaceutically acceptable excipients. The pellets may be compressed into tablets or filled in capsules of suitable size to obtain the compositions.
In one embodiment, a controlled release pharmaceutical composition of tolterodine is prepared by;
preparing an inert core;
coating the inert core with tolterodine and a binder selected from the group
consisting of saccharide, sugar alcohol, or mixtures thereof;
coating the tolterodine-coated core with one or more release modifying
polymer and optionally one or more pharmaceutically acceptable excipients
to obtain pellets; and
compressing the pellets into a tablet or filling into a capsule to obtain the
pharmaceutical composition.

In another embodiment, a controlled release pharmaceutical composition of tolterodine is prepared by;
preparing a core by granulating tolterodine and one or more phamnaceutically
acceptable excipients;
coating the core with tolterodine and a binder selected from the group
consisting of saccharide, sugar alcohol, or mixtures thereof;
coating the tolterodine-coated core with a release modifying polymer and
optionally one or more pharmaceutically acceptable excipients to obtain
pellets; and
compressing the pellets into a tablet or filling into a capsule to obtain the
pharmaceutical composition.
In another embodiment, a controlled release pharmaceutical composition of
tolterodine is prepared by;
preparing a core by granulating tolterodine, a release modifying polymer and optionally one or more pharmaceutically acceptable excipients, drying the granules, mixing the granules with one or more pharmaceutically acceptable excipients, and compressing the mixture into a tablet; and coating the tablet with a release modifying polymer and optionally one or more pharmaceutically acceptable excipients.
The pharmaceutical compositions as described herein may be illustrated by the following example which is not to be construed as limiting the scope of the invention:

EXAMPLES 1 - 2

Ingredients Quantity (Mg / Capsule)

Example 1 Example 2
Microcrystalline cellulose sphere 130.0 130.0
Tolterodine tartrate 4.0 4.0
Sucrose 4.0 4.0
Ethylcellulose 10.7 -
Hydroxypropyl methylcellulose 2.7 2.7
Surelease® - 17.4
Talc 4.4 4.4
Methanol q.s. -
Methylene chloride q.s. -
Purified water q.s. q.s.
Total 155.8 152.5
Surerelease®: 25 % w/w aqueous ethyl cellulose dispersion containing oleic acid and dibutyl sebacate, commercially marketed by Colorcon
PROCEDURE: Tolterodine tartarate and sucrose were dissolved in water. Talc was added in the solution and the solution was sprayed on microcrystalline cellulose spheres in a fluid bed processor. Ethyl cellulose (Example 1) / Surerelease® (Example 2), hydroxypropyl methyl cellulose and talc were dissolved in a mixture of methanol and methylene chloride (Example 1) / Water (Example 2) and the solution was sprayed over tolterodine-coated spheres. The pellets were dried and filled in a capsule of suitable size.
EXAMPLES 3 - 4

Ingredients Quantity (M g / Capsule)

Example 3 Example 4
Tolterodine tartrate 4.0 4.0
Microcrystalline cellulose 130.0 130.0
Sucrose 4.0 4.0
Ethylcellulose 10.7 -
Hydroxypropyl methylcellulose 2.7 2.7
Surelease® - 17.4
Talc 4.4 4.4
Methanol q.s. q.s.
Methylene chloride q.s. q.s.
Purified water q.s. q.s.
Total 155.8 162.5

Surerelease®: 25 % w/w aqueous ethyl cellulose dispersion containing oleic acid and dibutyl sebacate, commercially marketed by Colorcon
PROCEDURE: A part of tolterodine tartarate was dissolved in water and microcrystalline cellulose was granulated with the solution in a fluid bed processor. The granules were dried and sifted. The remaining amount of tolterodine tartarate, sucrose and talc were dissolved in water and the solution was sprayed on tolterodine granules. Ethyl cellulose (Example 1) / Surerelease® (Example 2), hydroxypropyl methylcellulose and talc were dissolved in a mixture of methanol and methylene chloride (Example 1) / Water (Example 2) and the solution was sprayed over tolterodine-coated granules. The pellets were dried and filled in a capsule of suitable size.
EXAMPLE 5

Ingredients Quantity
(Mg/ Capsule)
Tolterodine tartrate 2.0
Lactose 41.6
Hydroxypropyl methylcellulose (viscosity between 1-100 cps) 1.5
Hydroxypropyl methylcellulose (viscosity between 3000-6000 cps) 14.0
Ethyl cellulose 0.3
Talc 0.2
Colloidal silicon dioxide 0.2
Magnesium stearate 1.0
Triethyl citrate 0.2
Titanium dioxide 0.5
Isopropyl alcohol q.s.
Methylene chloride q-s.
Total 61.5
PROCEDURE: Tolterodine tartarate, lactose and a part of hydroxypropyl methylcellulose were mixed and granulated with a solution of hydroxypropyl methylcellulose. The granules were dried and mixed with hydroxypropyl methylcellulose, colloidal silicon dioxide and magnesium stearate, and the mixture was compressed into a tablet using an appropriate tooling. A coating dispersion was

prepared by dissolving ethyl cellulose, hydroxypropyl methylcellulose, triethyl citrate, titanium dioxide and talc in a mixture of isopropyl alcohol and methylene chloride and the dispersion was coated on the tablet. One or more tablets were filled in a capsule of suitable size.
EXAMPLE 6

Ingredients Quantity (Mg / Capsule)
Tolterodine tartrate 2.0
Lactose 41.6
Hydroxypropyl methylcellulose 1.0
Polyethylene oxide 14.0
Ethyl cellulose 1.6
Talc 0.2
Colloidal silicon dioxide 0.2
Magnesium stearate 1.0
Tri ethyl citrate 0.2
Isopropyl alcoboi q.s.
Methylene chloride q.s.
Total 61.8
PROCEDURE: Tolterodine tartarate and lactose were mixed and granulated with a solution of hydroxypropyl methylcellulose. The granules were dried and mixed with polyethylene oxide, colloidal silicon dioxide and magnesium stearate, and the mixture was compressed into a tablet using an appropriate tooling. A coating dispersion was prepared by dissolving ethyl cellulose, triethyl citrate and talc in a mixture of isopropyl alcohol and methylene chloride and the dispersion was coated on the tablet. One or more tablets were filled in a capsule of suitable size.

EXAMPLE 7

Ingredients Quantity (Mg / Capsule)
Tolterodine tartrate 2.0
Lactose 18.0
Polyethylene oxide 40.0
Magnesium stearate 1.0
Ethyl cellulose 1.6
Triethyl citrate 0.2
Talc 0.2
Isopropyl alcohol q.s.
Methylene chloride q.s.
Total 63.0
PROCEDURE: Tolterodine tartarate, lactose, polyethylene oxide and magnesium stearate were mixed and compacted in a roller compactor. The compacts were milled to obtain granules of desired size. The granules were compressed into a tablet using' appropriate tooling. A coating dispersion was prepared by dissolving ethyl cellulose, triethyl citrate and talc in a mixture of isopropyl alcohol and methylene chloride and the dispersion was coated on the tablet. One or more tablets were filled in a capsule of suitable size.
EXAMPLE 8

Ingredients Quantity (Mg / Capsule)
Tolterodine tartrate 2.0
Lactose 27.0
Hydrogenated castor oil 30.0
Magnesium stearate 1.0
Ethyl cellulose 1.6
Triethyl citrate 0.2
Talc 0.2
Isopropyl alcohol q.s.
Methylene chloride q.s.
Total 62.0
PROCEDURE: Tolterodine tartarate, lactose, hydrogenated castor oil and magnesium stearate were mixed and compacted in a roller compactor. The compacts were milled to obtain granules of desired size. The granules were

compressed into a tablet using appropriate tooling. A coating dispersion was prepared by dissolving ethyl cellulose, triethyl citrate and talc in a mixture of isopropyl alcohol and methylene chloride and the dispersion was coated on the tablet. One or more tablets were filled in a capsule of suitable size.
The dissolution profile of capsule (filled with pellets) of Example 2 is depicted in Tablet
Table 1: Comparative dissolution profiles of Example 2 and Reference product in USP type I dissolution apparatus in 900 ml of phosphate buffer (pH 6.8), 100 rpm, 37 ± 0.5 °C

Time (in hours) % tolterodine dissolved

Example 2 Reference product*
0 0.0 0.0
0.5 2.4 4.9
1 9.1 10.1
2 27.7 26.0
3 44.5 45.2
5 68.1 73.3
7 81.1 84.8
9 88.2 88.5
•Reference product refers to Tolterodine Tartatate Extended Release Capsule (4 mg), sold under the brand name DETROL® LA by Pfizer in USA
As is evident from Table 1, the compositions as described herein exhibit controlled release of tolterodine which is comparable to the Reference product.

WE CLAIM:
1) A controlled release pharmaceutical composition comprising one or more units,
wherein the unit comprises:
(i) an inert core;
(ii) a first coat coated on the core comprising tolterodine and a binder selected
from the group consisting of saccharides, sugar alcohols, and mixtures
thereof; and (iii) a second coat on the first coat comprising a release modifying polymer and one or more pharmaceutically acceptable excipients.
2) The composition of claim 1, wherein the release modifying polymer is selected from a hydrophilic polymer, a hydrophobic polymer, or mixtures thereof.
3) The composition of claim 2, wherein the hydrophobic release modifying polymer is selected from a group consisting of ethylcellulose, polymethacrylates, polyacrytate, polyvinyl acetate, cellulose acetate, cellulose propionate, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, beeswax, carnauba wax, microcrystalline wax, cetostearyl alcohol, stearyl alcohol, cetyl alcohol, myristyl alcohol, glyceryl monostearate, glyceryl distearate, glycerol monooleate, acetylated monoglycerides, tristearin, tripalmitin, glyceryl palmitostearate, glyceryl behenate, hydrogenated castor oil, and mixtures thereof.
4). The composition of claim 1, wherein the inert core comprises at least one of sugar spheres or microcrystalline cellulose.
5) The composition of claim 1, wherein the composition further comprises a
pharmaceutically acceptable excipient selected form a group consisting of diluent,
disintegrant, plasticizer, opacifier, glidant, lubricant or anti-adherent.
6) A process for preparing a controlled release pharmaceutical composition, wherein
the process comprises:

(a) providing an inert core;
(b) coating the inert core with tolterodine and a binder selected from the group consisting of saccharide, sugar alcohol, or mixtures thereof; and
(c) coating the drug-coated core of step (b) with one or more release modifying polymer and optionally one or more pharmaceutically acceptable excipients;
(d) optionally mixing the product of step (c) with one or more pharmaceutically acceptable excipients; and
(e) compressing the product of step (c) or (d) into a tablet or filling into a capsule to obtain the pharmaceutical composition.
7) A controlled release pharmaceutical composition comprising one or more units,
wherein the unit comprises:
(i) a core comprising tolterodine;
(ii) a first coat coated on the core comprising tolterodine and a binder
selected from the group consisting of saccharides, sugar alcohols, and
mixtures thereof; and (iii) a second coat on the first coat comprising a release modifying polymer
and one or more pharmaceutically acceptable excipients.
8) A controlled release pharmaceutical composition comprising:
(i) a core comprising
a) tolterodine;
b) a release modifying polymer; and
(ii) a coating on the core comprising a release modifying polymer and one or more pharmaceutically acceptable excipients.
9) A controlled release pharmaceutical composition comprising:
(i) a core comprising
a) tolterodine;
b) hydroxypropyl methylcellulose comprising viscosity in the range of 1 cps to 100 cps; and

c) hydroxypropyl methylcellulose comprising viscosity in the range of
3000 cps to 6000 cps; (ii) a coating on the core comprising a release modifying polymer and one or more pharmaceutically acceptable excipients.
10) A controlled release pharmaceutical composition of tolterodine as substantially described and exemplified herein.