FIELD OF THE INVENTION
The present invention relates to a modified release pharmaceutical dosage forms
comprising Cyclobenzaprine and methods of manufacture.
BACKGROUND OF THE INVENTION
Cyclobenzaprine hydrochloride, a skeletal muscle relaxant, is a centrally acting drug
which reduces or abolishes excessive tonic muscle activity in hypertonic as opposed to
hyperphasic disorders. The immediate release dosage forms relieve skeletal muscle
spasm of local origin without interfering with muscle function. Immediate release dosage
forms are required to be administrated more than once daily. This leads to patient non-
compliance, especially with the elderly patients.
US Pat. No. 7,387,793 assigned to Eurand Inc provides a modified release, multi-
particulate dosage form of Cyclobenzaprine hydrochloride comprising one or more bead
populations, which provides an extended release profile. Bead population typically
comprises an immediate release core formed by coating drug onto an inert particle.
Further a coating comprising water insoluble polymer alone, or in combination with
water-soluble polymer is applied onto the active containing cores.
US 2003/0180362 assigned to Pacific corporation discloses a novel delivery system for
controlling drug release comprising granules comprising a drug and a hydrophobic carrier
embedded in a swelling-erodible matrix which is covered by a hydrophobic release
modifying layer.
US 2006/0018934 assigned to Torrent pharmaceuticals relates to a dual retard modified
release dosage form comprising micromatrix comprising an active agent and hydrophobic
release controlling agent further coated by hydrophobic release controlling agent to form
a double barrier which controls the diffusion of the active agent.

US 2006/0018933 assigned to Torrent pharmaceuticals relates to a dual retard modified
release dosage form comprising micromatrix comprising an active agent and hydrophobic
release-controlling agent. This is further coated by release a controlling agent, which
forms a diffusion controlled double barrier for the active agent.
We have developed a modified release pharmaceutical dosage form comprising
Cyclobenzaprine hydrochloride and release controlling agent to reduce the problem of
patient compliance as observed in immediate release dosage forms.
OBJECTS OF THE INVENTION
The object of the present invention is a modified release pharmaceutical dosage form
comprising a core comprising Cyclobenzaprine, pharmaceutically acceptable salts or
derivatives and mixtures thereof and one or more release controlling agent(s).
Another object of the present invention is a modified release pharmaceutical dosage form
comprising a first component comprising a core comprising Cyclobenzaprine,
pharmaceutically acceptable salts or derivatives and mixtures thereof and one or more
release controlling agent(s); and a second component comprising a core comprising
Cyclobenzaprine, pharmaceutically acceptable salts or derivatives and mixtures thereof
and one or more release controlling agent(s) and; an extended release coating on the core.
Further object of the invention is to provide a process for the preparation of a modified
release pharmaceutical dosage form.
Yet another object of the present invention is a modified release pharmaceutical dosage
form comprising a) a core comprising Cyclobenzaprine, pharmaceutically acceptable
salts or derivatives and mixtures thereof and one or more release controlling agent(s),
wherein said dosage form when dissolution tested using United States Pharmacopoeia
Apparatus 2 (paddles @ 50 rpm) in 900 mL of 0.1N HC1 at 37°C exhibits a drug release
profile substantially corresponding to the following pattern: after 2 hours, no more than
about 40% of the total active is released; after 4 hours, from about 40-65% of the total

active is released; after 8 hours, from about 50-75% of the total active is released; after
16 hours, from about 65-80% of the total active is released; and after 24 hours no less
than about 75% of the total active is released.
Yet another object of the present invention is a modified release pharmaceutical dosage
form comprising two components comprising: a) a first component comprising a core
comprising Cyclobenzaprine, its pharmaceutically acceptable salts or derivatives and
mixtures thereof and one or more release controlling agent(s); and b) a second component
comprising a core comprising Cyclobenzaprine, its pharmaceutically acceptable salts or
derivatives and mixtures thereof and one or more release controlling agent(s) and; an
extended release coating on the core, wherein said dosage form when dissolution tested
using USP Apparatus 2 (paddles @ 50 rpm) in 900 mL of 0.1N HC1 at 37°C exhibits a
drug release profile substantially corresponding to the following pattern: after 2 hours, no
more than about 40% of the total active is released; after 4 hours, from about 40-65% of
the total active is released; after 8 hours, from about 50-75% of the total active is
released; after 16 hours, from about 65-80% of the total active is released; and after 24
hours no less than about 75% of the total active is released.
A further object of the present invention is a modified release pharmaceutical dosage
form comprising a core comprising Cyclobenzaprine, its pharmaceutically acceptable
salts or derivatives and mixtures thereof and one or more release controlling agent(s)
used to teat disorders involving skeletal muscle hypertonic activity.
Another object of the present invention is a process for manufacture of a modified release
pharmaceutical dosage form comprising a first component comprising a core comprising
a mixture of Cyclobenzaprine, pharmaceutically acceptable salts or derivatives and
mixtures thereof and one or more release-controlling agent(s), which is loaded onto inert
beads and second component comprising a core comprising a mixture of
Cyclobenzaprine, its pharmaceutically acceptable salts or derivatives and mixtures
thereof and one or more release-controlling agent(s), which is loaded onto inert beads;
and an extended release coating on the said core.

Another object of the present invention is modified release pharmaceutical dosage form
comprising two components a) a first component comprising a core comprising
Cyclobenzaprine, pharmaceutically acceptable salts or derivatives and mixtures thereof
and one or more release controlling agent(s); and b) second component comprising a core
comprising Cyclobenzaprine, its pharmaceutically acceptable salts or derivatives and
mixtures thereof and one or more release controlling agent(s) and; an extended release
coating on the core used to treat disorders involving skeletal muscle hypertonic activity.
SUMMARY OF THE INVENTION
The present invention relates to a modified release dosage form comprising
cyclobenzaprine its pharmaceutically acceptable salts or derivatives and mixtures thereof
and one or more release-controlling agent(s). This composition is manufactured by
preparing a core comprising Cyclobenzaprine or its pharmaceutically acceptable salt and
one or more release-controlling agent(s).
The present invention also relates to a modified release pharmaceutical dosage form
comprising two components a) a first component comprising a core comprising
cyclobenzaprine, pharmaceutically acceptable salts or derivatives and mixtures thereof
and one or more release-controlling agent(s); and b) a second component comprising a
core comprising cyclobenzaprine, pharmaceutically acceptable salts or derivatives and
mixtures thereof and one or more release-controlling agent(s) and; an extended release
coating. This composition is formulated by preparing the first component comprising a
core comprising cyclobenzaprine or its pharmaceutically acceptable salt and one or more
release controlling agent; and preparing the second component comprising preparing a
core comprising cyclobenzaprine or its pharmaceutically acceptable salt and one or more
release controlling agent; and coating the core with an extended release coating; and
finally combining the first and the second components in a ratio ranging from 1:3 to 3:1.
The invention is used to treat disorders involving skeletal muscle hypertonic activity.
Disorders involving skeletal muscle activity include disorders of the group comprising
muscle spasm, muscle spasticity, muscle rigidity or muscle splinting.

DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a modified release dosage form comprising
Cyclobenzaprine pharmaceutically acceptable salts, derivatives or mixtures thereof and
one or more release-controlling agent(s) and an optional extended release coating.
In another embodiment the present invention also relates to a modified release
pharmaceutical dosage form comprising two components comprising a first component
comprising a core comprising Cyclobenzaprine, pharmaceutically acceptable salts or
derivatives or mixtures thereof, and one or more release controlling agent(s); and a
second component comprising a core comprising Cyclobenzaprine, pharmaceutically
acceptable salts, derivatives or mixtures thereof, one or more release controlling agent(s)
and an extended release coating on the core. A seal coat may be applied over the core.
The two components may be combined in a ratio of 1:3 to 3:1. The various components of
the formulation will be discussed individually along with the methods of preparation as
follows.
The terms "Cyclobenzaprine" or "active" encompass various pharmaceutical derivatives,
complexes, salts, hydrates, polymorphs, esters etc of Cyclobenzaprine or mixtures
thereof.
The term dosage form includes but is not limited to solutions and/or suspensions,
dispersions, concentrates, ready mix, powders, granules, tablets, micro-tablets, capsules,
pellets, discrete particles or beads comprising Cyclobenzaprine.
The term "seal coating layer" is synonymous to various terms like separating layer, seal
coating layer, intermediate layer, barrier coating layer, outer coating layer and the likes.
The term "modified release dosage form" means any dosage form other than immediate
release dosage form.

The modified release dosage form according to the present invention comprises but is not
limited to a dosage form substantially as herein described, and in particular a tablet or
capsule or minitablets or granules or pellets or beads filled in capsule.
The core
The core comprises Cyclobenzaprine, one or more release-controlling agent(s) and/or one
or more pharmaceutically acceptable excipients.
The release-controlling agents:
The release-controlling agent(s) may be hydrophilic or hydrophobic.
The hydrophilic release controlling agents are selected from a group comprising but not
limited to cellulose and cellulose derivatives such as, hydroxypropyl methylcellulose,
hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, sodium
carboxymethyl cellulose (CMC); gums selected from xanthan gum, karaya gum, locust
bean gum, alginic acid and sodium alginate; agar, poloxamers, starch and its derivatives,
polyethylene glycols, polyethylene oxides, polyvinyl pyrrolidone, polyvinyl alcohol,
polyoxyethylene alkyl ethers, chitosan, poly(hydroxymethacrylates), poly(hydroxyethyl
methacrylates), acrylamides, polyacrylates;, polyacrylamides, poly hydroxybutyl
acrylate, and poly 2-hydroxyethyl methacrylates or mixtures thereof.
The hydrophobic release controlling agents may be selected from a group comprising but
not limited to ethylcellulose, cellulose acetate, cellulose propionate; cellulose acetate
propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate,
ammonio methacrylate copolymers type A and B; methacrylic acid copolymer type A, B
and C; polyacrylate dispersion 30%; polyvinyl acetate dispersion, poly(methyl
methacrylate), poly(ethyl methacrylate), poly(butyl methacrylate), poly(isobutyl
methacrylate), poly (hexyl methacrylate), poly(isodecyl methacrylate), poly (lauryl
methacrylate), poly(phenyl methacrylate), poly (methyl acrylate), poly (isopropyl
acrylate), poly (isobutyl actylate), poly (octadecyl acrylate), vegetable oils, hydrogenated
vegetable oils, waxes; fatty alcohols; and fatty acid esters.

The release-controlling agent is present in the invention in the range of 10% to 90% by
weight.
One or more pharmaceutically acceptable excipients are selected from the group
comprising but not limited to diluents, fillers, binders, glidants, lubricants, inert beads,
and mixtures thereof.
Fillers or diluents, which include, but are not limited to confectioner's sugar,
compressible sugar, dextrates, dextrin, dextrose, fructose, lactitol, mannitol, sucrose,
starch, lactose, trehalose, xylitol, sorbitol, talc, microcrystalline cellulose, calcium
carbonate, calcium phosphate dibasic or tribasic, calcium sulphate, polymethacrylates,
povidone, simethicone, sodium chloride, tragacanth and mixtures thereof.
Binders include, but are not limited to, povidone, starch, dextrose, lactose, sodium
alginate, acacia, agar and its derivatives, carbomers, cellulose and its derivatives,
chitosan, crospovidone CMC, polyvinyl pyrrolidone, polyethylene glycol and mixtures
thereof.
Glidants include, but are not limited to, silicon dioxide; stearic acid and its salts,
magnesium oxide, calsium silicate, magnesium trisilicate, powdered cellulose, starch, talc
tribasic calcium phosphate and mixtures thereof.
Lubricants may be selected from, but are not limited to, those conventionally known in
the art such as stearate salts of Magnesium, Aluminium, Calcium or Zinc; talc and the
likes.
Inert beads are selected from but not limited to sugar spheres, microcrytalline cellulose
spheres, starch beads, lactose beads, and mixtures thereof.

Seal Coating/Overcoat:
The seal-coating layer may be applied over the core or between the core and the extended
release coating. The function of this layer is to provide a smooth surface. The seal-coat is
preferably composed of a substance or a mixture of such substances that does not react or
affect the stability of the core comprising Cyclobenzaprine or its pharmaceutically
acceptable salts or derivatives thereof; nor adversely affects its bioavailability or release.
Typical examples of substances that can be used in the seal-coat include but are not
limited to organic or inorganic polymers, sugars and the likes. The seal coat may
optionally further comprise additional pharmaceutically acceptable excipients like
plasticizers, thickening agents, glidants, opacifiers and coloring agents Preferably, the
additional pharmaceutically acceptable excipients are selected from talc, silicon dioxide,
and titanium dioxide
Extended Release Coating:
The extended release coat is applied to accomplish modified release of the
Cyclobenzaprine. The extended release coat is comprised of an extended release agent,
which is either hydrophobic, hydrophilic, or mixtures thereof.
The hydrophilic agent is selected from a group comprising but not limited to cellulose
and its derivatives, gums selected from xanthan gum, karaya gum, locust bean gum,
alginic acid and sodium alginate; agar, poloxamers, starch and its derivatives,
polyethylene glycols, polyethylene oxides, polyvinyl pyrrolidone, polyvinyl alcohol,
polyoxyethylene alkyl ethers, chitosan, poly(hydroxymethacrylates), poly(hydroxyethyl
methacrylates), acrylamides, polyacrylates; polyacrylamides, poly hydroxybutyl
acrylate, and poly 2-hydroxyethyl methacrylates.
The hydrophobic agent is selected from a group comprising but not limited to
ethylcellulose, cellulose acetate, cellulose propionate; cellulose acetate propionate,
cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, ammonio
methacrylate copolymers type A and B; methacrylic acid copolymer type A, B and C;
polyacrylate dispersion 30%; polyvinyl acetate dispersion, poly(methyl methacrylate),

poly(ethylmethacrylate), poly(butylmethacrylate), poly(isobutylmethacrylate), poly
(hexylmethacrylate), poly(isodecylmethacrylate), poly (lauryl methacrylate), poly(phenyl
methacrylate), poly (methylacrylate), poly (isopropylacrylate), poly (isobutylacrylate),
poly (octadecylacrylate), vegetable oils, hydrogenated vegetable oils, waxes; fatty
alcohols; and fatty acid esters.
The extended release agent is present in the coating in the range of 10% to 90% by
weight.
Additionally one or more pharmaceutically acceptable excipients may be incorporated
with the extended release agent. These are selected from group comprising of but not
limited to plasticizers, antitacking agents, opacifiers, coloring agents, and the likes.
Plasticizers may be selected from a group comprising but not limited to acetyl tributyl
citrate, bezoates, dextrins, alkylcelluloses, dibutyl pthalate, dibutyl sebacate, diethyl
phtalate, dimethyl pthalate, ethylcellulose, sorbitol, mannitol, glycerine, triacetin,
polyethylene glycols, pyrrolidone and mixtures thereof.
The coatings may be applied as suspension or solution in aqueous or organic solvents.
One of the embodiment of the present invention describes the process to manufacture the
modified release dosage forms comprising Cyclobenzaprine its pharmaceutically
acceptable salts, derivatives or mixtures thereof and one or more release-controlling
agent(s) and an optional extended release coating.
The core may be prepared by mixing Cyclobenzaprine and the one or more release-
controlling agent(s). The mixing here may be purely physical mixing, deposition,
adsorption, aggregation or adhesion and the likes. This mixture may be further granulated
using a suitable binder and compressed. Alternately the said mixture may be directly
compressed. In another embodiment, the said mixture may be slugged to give large

compacts. These compacts may be milled to obtain granules, which may further be
compressed. The compressed cores may have a size ranging from 1.5 mm to 4.5 mm.
Alternately, the mixture may be extruded to form pellets. In another embodiment,
Cyclobenzaprine and one or more pharmaceutically acceptable excipients are loaded onto
inert beads. The pellets or beads may have size ranging from 500µm to 1500µm.
The core may be coated with a seal coating layer. The seal coated cores may then be
coated further with extended release coating. The application of seal coating layer is
optional.
The coating may be applied using any known technique, which include without any
limitation powder coating, spraying, pan coating, and the likes. Each layer is applied in
the form of a suspension or a solution. The layers are dried prior to the application of the
next successive coating.
Before the subject invention is described further, it is to be understood that the invention
is not limited to the particular embodiments of the invention.
Examples:
Example I
Part I - Core

Cyclobenzaprine hydrochloride and carbopol were sifted through a suitable sieve and
mixed together. The mixture was further granulated using suitable solvent. The granules
were dried, lubricated and finally compressed.

The cores may be coated with a seal-coating layer comprising hypromellose in a suitable
solvent system and dried.
Part II - Extended release coating

Polymethacrylic acid ethylacrylate copolymer and hypromellose were dissolved in a
suitable solvent system to form a coating solution. Talc was dispersed in the above
solution and stirred to get a homogenous dispersion. The final dispersion was sprayed
onto the cores. The cores were dried and finally filled into capsules.
Example II
Part I - Core

Cyclobenzaprine hydrochloride, Dibasic Calcium Phosphate anhydrous and
Hypromellose were sifted through a suitable sieve and mixed. The mixture was
granulated using a binder solution of Polyvinylpyrrolidone. The granules were dried,
lubricated and finally compressed.
The cores may be coated with a seal-coating layer comprising hypromellose in a suitable
solvent system and dried.


Part II - Extended release coating
Ethylcellulose and Hypromellose were dissolved in a suitable solvent system to form a
uniform coating solution. The solution was sprayed onto the cores. The cores were dried
and finally filled into capsules.
Example III
Component 1 - Extended Release cores
Part I - Core

Cyclobenzaprine hydrochloride, Dibasic Calcium Phosphate anhydrous and
Hypromellose were sifted through a suitable sieve and mixed. The mixture was
granulated using a binder solution of Polyvinylpyrrolidone. The granules were dried,
lubricated and finally compressed.
The cores were seal coated using a solution of hypromellose in a suitable solvent system
and dried.

Component 2 - extended release cores coated with extended release coating
Part I - Core

Cyclobenzaprine hydrochloride, Dibasic Calcium Phosphate anhydrous and Hydroxy
Propyl Methyl Cellulose were sifted through a suitable sieve and mixed together. The
mixture was granulated using a binder solution of Polyvinylpyrrolidone in isopropyl
alcohol. The granules were dried, lubricated and finally compressed.
The cores were seal coated using a solution of hypromellose in a suitable solvent system
and dried.
Part II - Extended release coating

Ethylcellulose and Hypromellose were dissolved in a suitable solvent system to form a
uniform solution. The solution was sprayed onto the above cores and the cores were
dried.
The above-formed cores of component 1 and component2 were then filled in a capsule


Example IV:
Cyclobenzaprine hydrochloride, hydrogenated vegetable oil and lactose monohydrate
were sifted through a suitable sieve and mixed. The mixture was subjected to melt
extrusion-spheronization. Pellets of desired size were cut, shaped and filled into capsules.
Exapmle V:
Part I - Core

Cyclobenzaprine, hypromellose and dibasic calcium phosphatre were mixed. The mixture
was spray coated onto inert beads using a binder solution. The beads so formed were
dried and sieved through suitable sieve.
The cores may be seal coated using a solution of hypromellose in a suitable solvent
system and dried.
Part II - Extended release coating


Ethylcellulose and Hypromellose were dissolved in a suitable solvent system to form a
uniform solution. The solution was sprayed onto the above cores and the cores were dried
and filled into capsules.
Exaple VI:
Component 1 - Extended Release cores
Part I - Core

Cyclobenzaprine, hypromellose and dibasic calcium phosphatre are mixed. The mixture
is spray coated onto inert beads using a binder solution. The beads so formed were dried
and sieved through suitable sieve to get uniform sized beads.
The beads may be seal coated using a solution of hypromellose in a suitable solvent
system and dried.
Component 2 - extended release cores coated with extended release coating
Part I - Core


Cyclobenzaprine, hypromellose and dibasic calcium phosphatre are mixed. The mixture
is spray coated onto inert beads using a binder solution. The beads so formed were dried
and sieved through suitable sieve.
The cores may be seal coated using a solution of hypromellose in a suitable solvent
system and dried.
Part II - Extended release coating

Ethylcellulose and Hypromellose were dissolved in a suitable solvent system to form a
uniform solution. The solution was sprayed onto the above beads and the beads were
dried.
The beads population of component 1 and component 2 was filled together in a capsule.
The invention also relates to a pharmaceutical dosage forms used for the treatment of
disorders involving skeletal muscle hypertonic activity comprising administering to a
patient in need thereof a modified release pharmaceutical dosage form as exemplified
above. Disorders involving skeletal muscle activity include disorders of the group
comprising muscle spasm, muscle spasticity, muscle rigidity or muscle splinting.
Dissolution
The in vitro specifications for generic products are established based on a dissolution
profile. In the case of a generic drug product, the dissolution specifications are generally
the same as the reference listed drug.
Dissolution was carried out in USP apparatus2 (Paddle apparatus) at 50 rpm in 900mL
0.1N HCL. The following compositions were tested: extended release capsule of
cyclobenzaprine hydrochloride (30mg) prepared according to example 3 as test and
Amrix® capsules (30mg) having cyclobenzaprine hydrochloride by Anseta as reference.

The results obtained are summarized below in table 1.
Tablel: Dissolution profile of Cyclobenzaprine hydrochloride 30mg extended
release capsule (Example III)


WE CLAIM :
1. A modified release pharmaceutical dosage form comprising a core comprising
Cyclobenzaprine, its pharmaceutically acceptable salts, derivatives or mixtures thereof
and one or more release controlling agent(s).
2. A modified release pharmaceutical dosage form in claim 1 is in the form of granules,
pellets, beads, discrete particles, minitablets, tablet, capsule or combinations thereof.
3. A modified release pharmaceutical dosage form in claim 1 wherein the one or more
release-controlling agent(s) may be hydrophilic or hydrophobic.
4. A modified release pharmaceutical dosage form in Claim 3 where the hydrophilic
release controlling agent is selected from a group comprising celluloses, hydroxypropyl
methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl
cellulose, sodium carboxymethyl cellulose; gums selected from xanthan gum, karaya
gum, locust bean gum, alginic acid and sodium alginate; agar, poloxamers, starch and its
derivatives, polyethylene glycols, polyethylene oxides, polyoxyethylene alkyl ethers,
chitosan, poly(hydroxymethacrylates), poly(hydroxyethyl methacrylates), acrylamides,
polyacrylates; polyvinyl pyrrolidone, polyvinyl alcohol, polyacrylamides, poly
hydroxybutyl acrylate, and poly 2-hydroxyethyl methacrylates and mixtures thereof.
5. A modified release pharmaceutical dosage form in claim 4 wherein the hydrophilic
release-controlling agent is preferably hydroxypropyl methylcellulose.
6. A modified release pharmaceutical dosage form in Claim 3 where the hydrophobic
release controlling agent is selected from a group comprising ammonio methacrylate
copolymers type A and B; methacrylic acid copolymer type A, B and C; polyacrylate
dispersion 30%; polyvinyl acetate dispersion, ethylcellulose, cellulose acetate, cellulose
propionate; cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate
phthalate, cellulose triacetate, poly(methyl methacrylate), poly(ethyl methacrylate),

poly(butyl methacrylate), poly(isobutyl methacrylate), poly (hexyl methacrylate),
poly(isodecyl methacrylate), poly (lauryl methacrylate), poly(phenyl methacrylate), poly
(methyl acrylate), poly (isopropyl acrylate), poly (isobutyl actylate), poly (octadecyl
acrylate), vegetable oils, hydrogenated vegetable oils, waxes, fatty alcohols; and fatty
acid esters and mixtures thereof.
7. A modified release pharmaceutical dosage form in claim 6 wherein the hydrophobic
release-controlling agent is preferably hydrogenated vegetable oil and/or wax.
8. A modified release pharmaceutical dosage form in claim 1, wherein the said dosage
form further comprises one or more pharmaceutically acceptable excipients selected from
the group comprising diluents, fillers, binders, glidants, lubricants, inert beads and
mixtures thereof.
9. A modified release pharmaceutical dosage form in claim 1, further comprises a seal
coating present on the core.

10. A modified release pharmaceutical dosage form in claim 1 further comprises an
extended release coating comprising one or more hydrophilic or hydrophobic agent(s) or
mixtures thereof.
11. A modified release pharmaceutical dosage form in claim 10, wherein hydrophobic
agent is selected from a group comprising ammonio methacrylate copolymers type A and
B; methacrylic acid copolymer type A, B and C; polyacrylate dispersion 30%; polyvinyl
acetate dispersion, ethylcellulose, cellulose acetate, cellulose propionate; cellulose acetate
propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate,
poly(methyl methacrylate), poly(ethyl methacrylate), poly(butyl methacrylate),
poly(isobutyl methacrylate), poly (hexyl methacrylate), poly(isodecyl methacrylate), poly
(lauryl methacrylate), poly(phenyl methacrylate), poly (methyl acrylate), poly (isopropyl
acrylate), poly (isobutyl actylate), poly (octadecyl acrylate), waxes; fatty alcohols; and
fatty acid esters and mixtures thereof.

11. The modified release pharmaceutical dosage form in claim 11, wherein the
hydrophobic agent is preferably ethyl cellulose.
12. A modified release pharmaceutical dosage form in claim 10, wherein the hydrophillic
agent is selected from a group comprising cellulose and its derivatives, gums selected
from xanthan gum, karaya gum, locust bean gum, alginic acid and sodium alginate; agar,
poloxamers, starch and its derivatives, polyethylene glycols, polyethylene oxides,
polyoxyethylene alkyl ethers, chitosan, poly(hydroxymethacrylates), poly(hydroxyethyl
methacrylates), acrylamides, polyacrylates; polyvinyl pyrrolidone, polyvinyl alcohol,
polyacrylamides, poly hydroxybutyl acrylate, and poly 2-hydroxyethyl methacrylates and
mixtures thereof.
13. A process for the preparation of a modified release pharmaceutical dosage form in
claim 1 comprising formulating a core comprising Cyclobenzaprine, its pharmaceutically
acceptable salts or derivatives and mixtures thereof and one or more release controlling
agent(s) and; optionally one or more coatings.
14. A process for manufacture of modified release pharmaceutical dosage form in Claim
1, wherein a mixture comprising Cyclobenzaprine pharmaceutically acceptable salts or
derivatives and mixtures thereof and one or more release-controlling agent(s) are loaded
onto inert beads using conventional techniques.
15. A modified release pharmaceutical dosage form comprising a) a core comprising
Cyclobenzaprine, its pharmaceutically acceptable salts or derivatives and mixtures
thereof and one or more release controlling agent(s), wherein said dosage form when
dissolution tested using United States Pharmacopoeia Apparatus 2 (paddles @ 50 rpm) in
900 mL of 0.1N HC1 at 37°C exhibits a drug release profile substantially corresponding
to the following pattern:
after 2 hours, no more than about 45% of the active is released;
after 4 hours, from about 25 - 65% of the active is released

after 8 hours, from about 45 - 85% of the active is released
after 16 hours, from about 65 - 95% of the active is released
after 24 hours, no less than about 70% of the active is released.
16. A modified release pharmaceutical dosage form comprising a core comprising
Cyclobenzaprine, its pharmaceutically acceptable salts or derivatives and mixtures
thereof and one or more release controlling agent(s); used to treat disorders involving
. skeletal muscle hypertonic activity.
17. A modified release pharmaceutical dosage form comprising two components:
a) first component comprising a core comprising Cyclobenzaprine, its pharmaceutically
acceptable salts or derivatives and mixtures thereof and one or more release controlling
agent(s); and
b) second component comprising i) a core comprising Cyclobenzaprine, its
pharmaceutically acceptable salts or derivatives and mixtures thereof and one or more
release controlling agent(s) and; ii) an extended release coating on the core.
18. A modified release pharmaceutical dosage form in claim 17, further comprising a seal
coating on the core.
19. A modified release pharmaceutical dosage form in claim 18 is in the form of
granules, pellets, beads, discrete particles, minitablets, tablet, capsule or combinations
thereof.
20. A modified release pharmaceutical dosage form in claim 17, wherein the said dosage
form further comprises one or more pharmaceutically acceptable excipients selected from
the group comprising diluents, fillers, binders, glidants, lubricants, inert beads and
mixtures thereof.
21. A process for the preparation of a modified release pharmaceutical dosage form in
claim 17 comprising:
a) preparing first component comprising a core comprising Cyclobenzaprine or its
pharmaceutically acceptable salt and one or more release controlling agent(s); and

b) preparing second component comprising i) preparing a core comprising
Cyclobenzaprine or its pharmaceutically acceptable salt and one or more release
controlling agent(s); and ii) coating the core with an extended release coating and;
c) combining the first and the second components in a ratio of 1:3 to 3:1.
22. A modified release pharmaceutical dosage form comprising two components:
a) a first component comprising a core comprising Cyclobenzaprine, its
pharmaceutically acceptable salts or derivatives and mixtures thereof and one or
more release controlling agent(s); and
b) a second component comprising a core comprising cyclobenzaprine,
pharmaceutically acceptable salts or derivatives and mixtures thereof and one or
more release controlling agent(s) and; an extended release coating on the core,
wherein said dosage form when dissolution tested using USP Apparatus 2
(paddles @ 50 rpm) in 900 mL of 0.1N HC1 at 37°C exhibits a drug release
profile substantially corresponding to the following pattern:
after 2 hours, no more than about 45% of the active is released;
after 4 hours, from about 25 - 65% of the active is released
after 8 hours, from about 45 - 85% of the active is released
after 16 hours, from about 65 - 95% of the active is released
after 24 hours, no less than about 70% of the active is released.
23. A process for manufacture of a modified release pharmaceutical dosage form in claim
17 comprising a) preparing first component comprising a core comprising
Cyclobenzaprine, pharmaceutically acceptable salts or derivatives and mixtures thereof
and one or more release-controlling agent(s) loaded onto inert beads and b) preparing
second component comprising a core comprising Cyclobenzaprine, pharmaceutically
acceptable salts or derivatives and mixtures thereof and one or more release-controlling
agent(s) loaded onto inert beads; and an extended release coating on the said core.
24. A modified release pharmaceutical dosage form in claim 23, which further comprises
a seal coating present on the core.

25. A modified release pharmaceutical dosage form comprising two components:
a) first component comprising a core comprising Cyclobenzaprine, pharmaceutically
acceptable salts or derivatives and mixtures thereof and one or more release
controlling agent(s); and
b) second component comprising i) a core comprising cyclobenzaprine,
pharmaceutically acceptable salts or derivatives and mixtures thereof and one or
more release controlling agent(s) and; ii) an extended release coating on the core
used to treat disorders involving skeletal muscle hypertonic activity.

The present invention relates to a modified release dosage forms comprising cyclobenzaprine its pharmaceutically acceptable salts or derivatives and mixtures thereof and one or more release-controlling agent(s) and processes to prepare them. The invention is used to treat disorders involving skeletal muscle hypertonic activity.