CLIAMS:
1. A process for the preparation of a modified release solid oral pharmaceutical composition comprising steps of:
(a) granulating cyclobenzaprine or salt thereof, at least one release modifying substance and at least one pharmaceutically acceptable excipient with a solvent to form granules;
(b) lubricating the granules of step (a) with pharmaceutically acceptable lubricant;
(c) compressing the lubricated granules of step (b) to form a mini-tablet, and
(d) coating the mini-tablet of step (c) with one or more water insoluble release modifying substances.

2. The process of claim 1, wherein the matrix in the mini-tablet does not constitute a coating.

3. The process of claim 1, wherein the ratio of the amount of cyclobenzaprine or salts thereof to the release modifying substances in the composition is in the range of about 1:1 to about 1:5.

4. The process of claim 1, wherein the ratio of the amount of cyclobenzaprine or salts thereof to the water soluble and/or insoluble release modifying substances in the composition is in the range of about 10:1 to about 2:1.

5. The process of claim 1, wherein said mini-tablet comprises about 5% w/w to about 85% w/w of cyclobenzaprine or salts thereof.

6. The process of claim 1, wherein the amount of release modifying substances in the composition ranges from about 15% w/w to about 85% w/w of the composition.

7. The process of claim 1, wherein the coated mini-tablet has dimension of more than 2 mm.

8. The process of claim 1, wherein the composition exhibits a release profile such that not more than about 40% of cyclobenzaprine or salts thereof is released in 2 hours, not less than 40% of cyclobenzaprine or salts thereof is released in 4 hours and not less than 60% of cyclobenzaprine or salts thereof is released in 8 hours when measured in 900 mL of 0.1N HCl at 37°C using USP Type II dissolution apparatus.

9. A process for the preparation of a capsule comprising steps of:
(a) granulating a dry blend comprising cyclobenzaprine or salt thereof, hydroxypropyl methylcellulose, methacrylic acid copolymer, lactose monohydrate and microcrystalline cellulose with a solvent to form granules;
(b) lubricating the granules of step (a) with magnesium stearate;
(c) compressing the lubricated granules of step (b) to form a mini-tablet;
(d) coating the mini-tablet of step (c) with a composition comprising ethylcellulose, polyvinyl pyrrolidone and triethyl citrate, and
(e) filling a single unit of the coated mini-tablet of step (d) in a capsule.
,TagSPECI:DESCRIPTION

The present invention provides a process for preparing a modified release solid oral pharmaceutical composition comprising cyclobenzaprine or salts thereof. In particular, the present invention relates to a process for preparing modified release solid oral pharmaceutical composition comprising a single unit of mini-tablet comprising cyclobenzaprine or salts thereof in a matrix of one or more release modifying substances, which mini-tablet is coated with one or more water soluble and/or insoluble release modifying substances. The composition may provide extended and specific release of cyclobenzaprine or salts thereof to achieve therapeutically effective plasma concentration over a period of 24 hours to treat muscle spasm associated with painful musculoskeletal conditions when administered to a patient in need thereof.

A spasm is a sudden, involuntary contraction of a muscle, a group of muscles. It most commonly refers to a muscle cramp which is often accompanied by a sudden burst of pain, but is usually harmless and ceases after a few minutes. There is a variety of other causes of involuntary muscle contractions, which may be more serious, depending on the cause. The spasm may also refer to a temporary burst of energy, activity, emotion, stress, or anxiety unrelated to, or as a consequence of, involuntary muscle activity.

Amongst causes of spasms are insufficient hydration, muscle overload, and absence of electrolytes. Spasmodic muscle contraction may be due to a large number of medical conditions, including the dystonias. A hypertonic muscle spasm is the state of chronic, excessive muscle tone, or tension in a resting muscle (the amount of contraction that remains when a muscle is not actively working).

A muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. Cyclobenzaprine functions as a muscle relaxant by blocking nerve impulses (or pain sensations) that are sent to your brain. Cyclobenzaprine is used together with rest and physical therapy to treat skeletal muscle conditions such as pain or injury.

Cyclobenzaprine is a tricyclic class of antidepressant, skeletal muscle relaxant. It is a white, crystalline tricyclic amine salt with the empirical formula C20H21N.HCl and a molecular weight of 311.9 and is designated chemically as 3-(5H-dibenzo [a, d] cyclohepten-5-ylidene)-N, N-dimethyl-1-propanamine and has the following structural formula:

Cyclobenzaprine is one of the routinely prescribed muscle relaxant approved and marketed in United States under the proprietary name Amrix® as extended release capsule by Teva.

Amrix® is indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions.

Many active pharmaceutical agents have been formulated as orally administrable extended release (over a period of time) dosage forms to permit once daily administration. The extended release of drug can be achieved either by coating the composition with release modifying substance or by dispersing drug in a matrix comprising one or more release modifying substances. In case of matrix-type dosage form, the drug is released over a period of time in the gastrointestinal tract upon erosion of the matrix.

Extended-release dosage forms comprising a matrix system are conveniently prepared as compressed tablets. But drugs having relatively high solubility in water, for example a solubility of about 10 mg/ml or greater, present challenges to the formulator wishing to provide an extended-release dosage form and the higher the solubility greater are the challenges.

U.S. Patent No. 5,582,838 discloses a drug delivery device for the controlled release of a beneficial agent. The drug delivery device includes a compressed core having at least two layers: at least one layer is a mixture of a beneficial agent and a polymer which forms microscopic polymer gel beads upon hydration and at least one outer layer comprises a polymer which forms microscopic polymer gel beads upon hydration. Water insoluble, water impermeable coating is applied to the core and the coating has apertures exposing between about 5-75% of the core surface.

PCT publication No. WO 2004/016249 discloses extended release matrix tablets for oral administration that include a cationic polymer, a water-swellable polymer, and an alginic acid derivative to cause the release rate of the active ingredient of the tablets to be independent of pH and gastric residence time.

PCT publication No. WO 2010/133961 discloses extended release pharmaceutical compositions comprising cyclobenzaprine or salts thereof in the form of an inert core coated with matrix type extended release layer. The drug may be coated onto inert core or may be present in matrix type extended release layer.

PCT publication No. WO 98/18610 discloses controlled release particles containing an active agent without substantial destruction of the matrix material. A release-rate controlling component is incorporated in a matrix to control the release rate of the encapsulant from the particles. A hydrophobic component or a high water binding capacity component may be used for extending the release time.

PCT publication No. WO 98/06439 discloses a composition comprising dug encapsulated in a matrix comprising a polyether ester copolymer, such as polyethylene glycol terephthalate/polybutylene-terephthalate copolymer. The polyether ester copolymer protects the active agent from degradation and thereby facilitates the drug delivery.

U.S. Patent No. 7,387,793 discloses modified release dosage forms wherein cyclobenzaprine extended release beads comprises active-containing core particle and an extended release coating of a water insoluble polymer membrane surrounding said core.

Several prior art references disclose different dosage forms comprising plurality of active ingredient containing units such as cores, pellets, beads and matrix tablets containing active ingredient coats. These dosage forms may be further coated with release modifying polymers.

Pellets provide desired release profile based on the amount and type of coating of release modifying substances. But the pelletization is sophisticated techniques which requires high end manufacturing facilities and add complexity to production process while consuming much of time and resources.

Thus, there exists an enduring need to develop a simple and improved modified release pharmaceutical composition of cyclobenzaprine which may provide an alternative to existing formulations to provide relief of muscle spasm associated with painful musculoskeletal conditions over a 24 hour period.

Also there exists a need to develop modified release pharmaceutical composition of cyclobenzaprine by using simple and economical process.

The inventors of the present invention have surprisingly found that it is possible to devise a simple composition of cyclobenzaprine or salts thereof comprising a single unit matrix mini-tablet coated with one or more water soluble and/or insoluble release modifying substances, which may provide therapeutically effective plasma concentration over a period of 24 hours. Such compositions can be used to treat muscle spasm associated with painful musculoskeletal conditions when administered to a patient in need thereof.

In one general aspect, there is provided a modified release solid oral pharmaceutical composition comprising:
(a) a single unit mini-tablet comprising matrix of cyclobenzaprine or salts thereof and one or more release modifying substances, and
(b) a coating comprising one or more water soluble release modifying substances;
wherein the coating is devoid of water soluble release modifying substances.

In another general aspect, there is provided a modified release solid oral pharmaceutical composition comprising:
(a) a single unit mini-tablet comprising matrix of cyclobenzaprine or salts thereof and one or more release modifying substances, and
(b) a coating comprising one or more water insoluble release modifying substances.

In another general aspect, there is provided a modified release solid oral pharmaceutical composition comprising:
(a) a single unit mini-tablet comprising matrix of cyclobenzaprine or salts thereof and one or more release modifying substances, which matrix does not constitute a coating, and
(b) a coating comprising one or more water soluble and/or insoluble release modifying substances.

In another general aspect, there is provided a modified release solid oral pharmaceutical composition; wherein cyclobenzaprine or salts thereof is dispersed in the matrix of one or more water soluble and/or insoluble release modifying substances and at least one pharmaceutically acceptable excipient to form the mini-tablet, which mini-tablet is coated with one or more water insoluble release modifying substances.

In another general aspect, the composition contains only one single coated mini-tablet.

In another general aspect, the coated mini-tablet has dimension of more than 2 mm, preferably more than 4 mm and more preferably more than 5 mm.

In another general aspect, the modified release solid oral pharmaceutical composition is in the form of a capsule filled with a single coated mini-tablet comprising matrix of cyclobenzaprine or salt thereof, one or more water soluble and/or insoluble release modifying substances and at least one pharmaceutically acceptable excipient; wherein said matrix does not constitute a coating.

In another general aspect, there is provided a modified release solid oral pharmaceutical composition, wherein the ratio of the amount of cyclobenzaprine or salts thereof to the release modifying substances in the composition is in the range of about 1:1 to about 1:5.

In another general aspect, there is provided a modified release solid oral pharmaceutical composition, wherein the ratio of the amount of cyclobenzaprine or salts thereof to the water soluble and/or insoluble release modifying substances in the composition is in the range of about 10:1 to about 2:1.

In another general aspect, there is provided a modified release capsule comprising a single unit mini-tablet, wherein said mini-tablet comprises about 0.1% w/w to about 95% w/w, preferably of about 5% w/w to about 85% w/w of cyclobenzaprine or salts thereof.

In another general aspect, there is provided a modified release solid oral pharmaceutical composition, wherein the amount of release modifying substances in the composition ranges from about 5% w/w to about 95% w/w, preferably about 15% w/w to about 85% w/w of the composition.

In another general aspect, the pharmaceutically acceptable excipients which may be used in the modified release solid oral pharmaceutical composition may be selected from, but not limited to diluent, binder, disintegrant, stabilizing agent, glidant, lubricant, and flavoring agents.

In another general aspect, there is provided a process for the preparation of a modified release solid oral pharmaceutical composition, which process comprises steps of:
(a) granulating cyclobenzaprine or salt thereof, at least one release modifying substance and at least one pharmaceutically acceptable excipient with a solvent to form granules;
(b) lubricating the granules of step (a) with pharmaceutically acceptable lubricant;
(c) compressing the lubricated granules of step (b) to form a mini-tablet, and
(d) coating the mini-tablet of step (c) with one or more water insoluble release modifying substances.

In another general aspect, there is provided a process for the preparation of a modified release solid oral pharmaceutical composition, which process comprises steps of:
(a) granulating a dry blend comprising cyclobenzaprine or salt thereof, hydroxypropyl methylcellulose, methacrylic acid copolymer, lactose monohydrate and microcrystalline cellulose with a solvent to form granules;
(b) lubricating the granules of step (a) with magnesium stearate;
(c) compressing the lubricated granules of step (b) to form mini-atblet, and
(d) coating the mini-tablet of step (c) with a composition comprising ethylcellulose, polyvinyl pyrrolidone and triethyl citrate.

In another general aspect, there is provided a process for the preparation of a capsule, which process comprises steps of:
(a) granulating a dry blend comprising cyclobenzaprine or salt thereof, hydroxypropyl methylcellulose, methacrylic acid copolymer, lactose monohydrate and microcrystalline cellulose with a solvent to form granules;
(b) lubricating the granules of step (a) with magnesium stearate;
(c) compressing the lubricated granules of step (b) to form mini-tablet;
(d) coating the mini-tablet of step (c) with a composition comprising ethylcellulose, polyvinyl pyrrolidone and triethyl citrate, and
(e) filling the single unit of coated mini-tablet of step (d) in a capsule.

In another general aspect, there is provided a method of treating muscle spasm associated with acute, painful musculoskeletal conditions by administering a modified release solid oral pharmaceutical composition comprising cyclobenzaprine or salts thereof in accordance of the present invention.

In another general aspect, there is provided a modified release solid oral pharmaceutical composition that exhibits a release profile such that not more than about 40% of cyclobenzaprine or salts thereof is released in 2 hours, not less than 40% of cyclobenzaprine or salts thereof is released in 4 hours and not less than 60% of cyclobenzaprine or salts thereof is released in 8 hours when measured in 900 mL of 0.1N HCl at 37°C using USP Type II dissolution apparatus.

The modified release solid oral pharmaceutical composition may provide therapeutically effective plasma concentration of cyclobenzaprine or salts thereof over a period of 24 hours.

In another general aspect, there is provided a modified release solid oral pharmaceutical composition characterized in that the dosage form is bioequivalent to the formulation of cyclobenzaprine marketed under the trade name Amrix®.

In another general aspect, there is provided a modified release solid oral pharmaceutical composition that retains at least 90% w/w of the potency of cyclobenzaprine or salt thereof when stored at 25°C and 40% relative humidity or at 40°C and 25% relative humidity for 3 months.

In another general aspect, there is provided a method of substantially minimizing the intersubject variability and improving the quality of life, especially in the elderly population, which method comprises administering the composition comprising cyclobenzaprine or salts thereof prepared in accordance of the present invention.

The modified release solid oral pharmaceutical composition of the present invention comprises a mini-tablet comprising a homogeneous matrix of cyclobenzaprine or its salt one or more release modifying substances, and one or more pharmaceutically acceptable excipients. The composition is preferably coated with water soluble and/or insoluble release modifying substances. More preferably, the matrix does not constitute a layer or coating. Such compositions may provide an extended release profile of cyclobenzaprine under in vitro conditions and may provide effective plasma concentration over a period of 24 hours.

The term “cyclobenzaprine” used throughout the specification refers to not only cyclobenzaprine per se, but also its other pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs and pharmaceutically acceptable prodrugs thereof.

The term "modified release" used throughout the specification shall apply to dosage forms, matrices, particles, coatings, portions thereof, or compositions that alter the release of an active ingredient in any manner. Types of modified release include controlled, prolonged, sustained, extended, delayed, and the likes.

The term “matrix” used throughout the specification refers to the dispersion of cyclobenzaprine within one or more release modifying substances and optionally one or more pharmaceutical excipients, or mixture thereof.

The term "pharmaceutically acceptable excipients" includes a pharmaceutically acceptable material, composition or vehicle, suitable for administering an active pharmaceutical ingredient. Each excipient should be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the subject/person/patient to whom it will be administered. Excipients include diluents, binders, disintegrants, glidants, lubricants, flavoring, and others.

In an embodiment, the modified release solid oral pharmaceutical composition comprising:
(a) a single unit mini-tablet comprising cyclobenzaprine or salts thereof in a matrix of one or more release modifying substances, and
(b) a coating comprising of one or more water soluble and/or insoluble release modifying substances.

The inventors of the present invention have also optimized the amount of the excipients those used in formulating the modified release solid oral pharmaceutical composition. In an embodiment, the ratio of the amount of cyclobenzaprine or salts thereof and release modifying substances in the composition is in the range of about 1:1 to about 1:5. In a further embodiment the ratio of the amount of cyclobenzaprine or salts thereof and water soluble and/or insoluble release modifying substances is in the range of about 10:1 to about 2:1.

The modified release unit dosage form of cyclobenzaprine or salts thereof may be developed in the form a capsule, a tablet, a caplet and a mini-tablet. Preferably the dosage form is in the form of a capsule. In an embodiment, the composition contains only one single coated mini-tablet.

The modified release solid oral pharmaceutical composition is preferably in the form of a capsule in which a single unit coated mini-tablet is filled.

The mini-tablet may have dimension of more than 2 mm, particularly more than 4 mm and preferably more than 5 mm.

The amount of cyclobenzaprine or salts thereof in the mini-tablet of the modified release solid oral pharmaceutical composition may range from about 0.1% w/w to about 95% w/w, preferably of about 5% w/w to about 85% w/w of the composition.

The amount of the release modifying substances in the modified release pharmaceutical composition may range from about 5% w/w to about 95% w/w, preferably about 15% w/w to about 85% w/w of the composition.

The release solid oral pharmaceutical composition, particularly the mini-tablet of the present invention may be prepared by various methods known to the person skilled in the art, including wet granulation, dry granulation, direct compression and slugging. Particularly preferred method includes wet-granulation followed by compression.

In an embodiment, the process for the preparation of a modified release solid oral pharmaceutical composition comprises steps of:
(a) granulating cyclobenzaprine or salt thereof, at least one release modifying substance and at least one pharmaceutically acceptable excipient with a solvent to form granules;
(b) lubricating the granules of step (a) with pharmaceutically acceptable lubricant;
(c) compressing the lubricated granules of step (b) to form a mini-tablet, and
(d) coating the mini-tablet of step (c) with one or more water insoluble release modifying substances.

In a further embodiment, the process for the preparation of a modified release solid oral pharmaceutical composition comprises steps of:
(a) granulating a dry blend comprising cyclobenzaprine or salt thereof, hydroxypropyl methylcellulose, methacrylic acid copolymer, lactose monohydrate and microcrystalline cellulose with a solvent to form granules;
(b) lubricating the granules of step (a) with magnesium stearate;
(c) compressing the lubricated granules of step (b) to form mini-tablet, and
(d) coating the mini-tablet of step (c) with a composition comprising ethylcellulose, polyvinyl pyrrolidone and triethyl citrate.

In a further embodiment, the process for the preparation of a modified release solid oral pharmaceutical composition comprises steps of:
(a) granulating a dry blend comprising cyclobenzaprine or salt thereof, hydroxypropyl methylcellulose, methacrylic acid copolymer, lactose monohydrate and microcrystalline cellulose with a solvent to form granules;
(b) lubricating the granules of step (a) with magnesium stearate;
(c) compressing the lubricated granules of step (b) to form mini-tablet;
(d) coating the mini-tablet of step (c) with a composition comprising ethylcellulose, polyvinyl pyrrolidone and triethyl citrate, and
(e) filling the single unit of coated mini-tablet of step (d) in a capsule.

The a modified release solid oral pharmaceutical composition in accordance with the present invention may exhibit a release profile such that not more than about 40% of cyclobenzaprine or salts thereof is released in 2 hours, not less than 40% of cyclobenzaprine or salts thereof is released in 4 hours and not less than 60% of cyclobenzaprine or salts thereof is released in 8 hours when measured in 900 mL of 0.1N HCl at 37°C using USP Type II dissolution apparatus.

In an embodiment, the modified release solid oral pharmaceutical composition characterized in that the dosage form is bioequivalent to the formulation of cyclobenzaprine marketed under the trade name Amrix®.

In another embodiment, the modified release solid oral pharmaceutical composition that retains at least 90% w/w of the potency of cyclobenzaprine or salt thereof when stored at 25°C and 40% relative humidity or at 40°C and 25% relative humidity for 3 months.

The release modifying substances used for preparing a matrix mini-tablet of cyclobenzaprine or salts thereof and coating over the mini-tablet may include both water soluble and water insoluble release modifying substances.

The release modifying substances which can be used in the composition of the present invention may be selected from the group consisting of hydrophilic agents (e.g. water-soluble polymers), lipophilic agents (water-insoluble polymers) and inert matrix agents, wherein the hydrophilic agents are selected from the group of pharmaceutical excipients which generate a gel in contact with water, including cellulose derivatives such as hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose and the like; non-cellulose polysaccharides such as galactomannanes, guar gum, carob gum, gum arabicum, alginates, pectins, and the like; polyvinylpyrrolidone; polyvinylacetate polymers and copolymers; acrylic acid polymers and copolymers, polyethylene oxide and mixtures thereof; the lipophilic agents are selected from the group consisting of waxes such as white wax, bees wax, carnauba wax and the like; fatty acids and alcohols such as stearic acid, palmitic acid, lauric acid and the like, and cetyl alcohol, cetostearyl alcohol, stearyl alcohol and the like; fatty acids esters such as monostearates of propylene glycol and fatty acid esters of sucrose, sucrose distearate and the like; and glycerides such as mono-, di- or triglycerides, e.g. palmitin, stearin, behenic, laurin, myristin, hydrogenated vegetable oil, castor oil, cottonseed oil, glyceril behenate and the like; ethyl cellulose; acrylic acid polymers and copolymers (available commercially under Eudragit® brand); and mixtures thereof; and the inert agents are selected from the group consisting of thermoplastic polymers, which are insoluble and indigestible in the gastrointestinal fluids, such as polyvinyl chloride, polyethylene, vinyl acetate/vinyl chloride copolymers, polymethylmethacrylates, polyamides, silicones, ethyl cellulose, polystyrene, and mixtures thereof.

Diluents increase the bulk of a solid pharmaceutical composition. Exemplary diluents for solid compositions include, but are not limited to microcrystalline cellulose, microfine cellulose, lactose, starch, pregelatinized starch, calcium carbonate, calcium sulfate, sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, polymethacrylates, potassium chloride, powdered cellulose, sodium chloride, sorbitol and talc.

Solid pharmaceutical compositions that are compressed may include excipients whose functions include helping to bind the active ingredient and other excipients together after compression which are know as binders. Exemplary binders for solid pharmaceutical compositions include, but are not limited to, acacia, alginic acid, carbomer, carboxymethylcellulose sodium, dextrin, ethyl cellulose, gelatin, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, liquid glucose, magnesium aluminum silicate, maltodextrin, methylcellulose, polymethacrylates, povidone, pregelatinized starch, sodium alginate and starch.

Disintegrants increase the dissolution rate of a compacted solid pharmaceutical composition in the patient's stomach, for example. Exemplary disintegrants include, but are not limited to, alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminum silicate, methyl cellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolate and starch.

Glidants can be added to improve the flowability of a non-compacted solid composition and to improve the accuracy of dosing. Exemplary excipients that may function as glidants include, but not limited to colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc and tribasic calcium phosphate.

A lubricant can be added to the composition to reduce adhesion and ease the release of the product from the dye. Exemplary lubricants include, but are not limited to magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc and zinc stearate.

The present invention further provides a method of treating muscle spasm associated with acute, painful musculoskeletal conditions by administering the modified release solid oral pharmaceutical composition comprising cyclobenzaprine or salts thereof as substantially described throughout the specification.

The modified release unit dosage form of cyclobenzaprine or salts thereof as substantially described throughout the specification can be administered for substantially minimizing the intersubject variability and improving the quality of life to a patient in need thereof.

In an embodiment, modified release unit dosage form of cyclobenzaprine or salts thereof as substantially described throughout the specification can be administered for treating muscle spasm associated with acute, painful musculoskeletal conditions to a patient in need thereof.

The present invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and do not limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Example 1: Cyclobenzaprine HCl Capsule
Table 1
Sr. No. Ingredients mg/ capsule
Intragranular
1 Cyclobenzaprine Hydrochloride 30.00
2 Hypromellose 2208 54.00
3 Lactose Monohydrate 60.00
4 Microcrystalline cellulose 55.00
5 Purified Water q. s.
Extragranular
6 Magnesium Stearate 1.00
Weight of core tablet 200.00
Coating
7 Ethylcellulose-10 FP 2.75
8 Triethyl citrate 0.5
9 PVP-K-30 1.75
10 Isopropyl alcohol (90%) q. s.
11 Water (10%) q. s.
Weight of coated tablet 210.00

Process: Cyclobenzaprine hydrochloride, hypromellose 2208, lactose monohydrate and microcrystalline cellulose were sifted and mixed to form dry powder blend. Thus formed dry powder blend was granulated using purified water to form granules. The obtained granules were dried and milled. The granules were lubricated with magnesium stearate and compressed to form core mini-tablets. The tablets were coated with a water insoluble coating composition comprising ethylcellulose, polyvinyl pyrrolidone and triethyl citrate and a single unit mini-tablet was filled in capsule.