FORM 2
THE PATENTS ACT 1970
(Act 39 of 1970)
&
THE PATENTS RULE, 2003
COMPLETE SPECIFICATION
(SECTION 10 and Rule 13)
TITLE OF THE INVETION
"A PHARMACEUTICAL COMPOSTION"
Emcure Pharmaceuticals Limited., an Indian company, registered under the Indian company's Act 1957
and having its registered office at
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Emcure House, T-184, M.I.D.C., Bhosari, Pune-411026, India.
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED:

A PHARMACEUTICAL COMPOSTION
FIELD OF THE INVENTION
The present invention relates to a novel, oral pharmaceutical composition of a therapeutically effective amount of a decongestant and a therapeutically effective amount of a piperidinoalkanol antihistaminic agent and to a process of preparation thereof.
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BACKGROUND OF THE INVENTION
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Rhinitis is defined as inflammation of the nasal membranes and is characterized by a symptom such as sneezing, nasal congestion, nasal itching, and rhinorrhea. The eyes, ears, sinuses, and throat can also be involved. Allergic rhinitis is the most common cause of rhinitis, affecting approximately 20% of the population worldwide. The causes of allergic rhinitis may differ depending on whether the symptoms are seasonal, perennial,
or sporadic/episodic. Seasonal allergic rhinitis is commonly caused by allergy to seasonal
I
pollens and outdoor molds. For complete symptomatic relief of rhinitis, it is a common practice to combine decongestants and antihistamines. Such combination therapy has been shown to possess better therapeutic activity than the therapy with either component alone and also helps to reduce the side effects of both agents.
Decongestants are adrenaline like drugs and work by constricting blood vessels in the lining of the nose thereby reducing the blood flowing through the area so that swollen tissue inside the nose shrinks and air can pass through more easily. Examples of oral nasal decongestant include pesudoephedrine, phenylephrine and phenylpropanolamines.
Histamine is one of the preformed mediators stored in mast cells and is released as a result of interaction of antigen with these cells. Histamine has important physiological roles and actions of histamine on bronchial smooth muscle and blood vessel account in part for symptoms of the allergic response. Antihistamines block the binding of histamines to histamine receptors in the nasal membranes. Antihistamines could be classified as sedative (first generation) and non-sedative (second generation) antihistamines. Therapeutically and commercially important second generation
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antihistamines belongs to alkylamine, piperazino alkylamine or piperidino alkyl amine chemical class. Examples of such antihistamines include terfenadine, loratidine, astemizole and fexofenadine.
Commercially available pharmaceuticals, dosage form containing decongestant and
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antihistamines generally provide a rapid release of the antihistamine and a controlled
i
release of decongestant. Allegra - D®, Claritin - D®, Seldane -:D® are some of the representative formulation, available worldwide that provide a rapid release of antihistamine and a controlled release of a decongestant. From the prescribing information of these products, it would be evident that these tablets are generally made for once or twice daily administration.
Further, many such pharmaceutical compositions are reported in the literature:
MacLaren et. al. in US 6,039,974 describes a pharmaceutical composition in the form of a bilayer tablet comprising (a) a first discrete zone made up with a therapeutically effective decongestant amount of a sympathomimetic drug or its salt with carnauba wax and a suitable antiadherent, which provides sustained release of the sympathomimetic drug; and (b) a second discrete zone made up of piperidinoalkanol Or a pharmaceutically acceptable salt in a second carrier base material comprising mixture of cellulose diluents in the preferable concentration of 27 to 73S % , binder in the preferable concentration of 15 to 30 %, disintegrant in the preferable -concentration of 0.25 to 6 % and lubricant in the preferable concentration of 0.25 to 2 %, wherein the said layer is prepared using aqueous wet granulation technique and provides an immediate release of the piperidinoalkanol or its pharmaceutically acceptable salt thereof.
US 6,267,986 of Jain et. al. discloses a process for the preparation [of a controlled drug delivery system comprising two discrete zones wherein the first discrete zone comprises pseudoephedrine as active ingredient alongwith hydrophilic polymer and group II metal ion salts of polyuronic acid, such as, sodium calcium alginate, and the second discrete zone comprises a long-acting antihistamine selected from the group consisting of loratadine, azatidine, fexofenadine, terfenadine, cetirizine, astemizole and levocabastine
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or their pharmaceutically acceptable salt as active ingredient. The first layer comprising pseudoephedrine is manufactured by roll compaction process and the second layer comprising antihistamine is manufactured by wet grainulation technique.
Webb et. al. in US 4,996,061 also disclosed a pharmaceutical composition in the form of tablet comprising of two discrete zones. The first discrete zone is made with formulation (A) comprising a therapeutically effective! decongestant amount of a sympathomimetic drug, one or more pharmaceutically acceptable water-soluble non-ionic cellulose ethers in an amount from about 18% to about 50% by weight of formulation (A), and one or more pharmaceutically acceptable excipients. The second discrete zone is made with formulation (B) comprising a therapeutically effective antilnstaminic amount of a piperidinoalkanol, calcium carbonate in an amount from about 0.5% to about 25% by weight of formulation (B), one or more pharmaceutically acceptable anionic surfactants in an amount from about 1% to about 10% by weight of formulation (B), and one or more pharmaceutically acceptable excipients. Formulation (B) may optionally contain a therapeutically effective decongestant amount of a sympathomimetic drug.
Further, Faour et. al. in US 7,147,870; US 6,613,357; and US 6,004,582 (RE 39,069)
discloses a multilayered osmotic device containing controlled release pseudoephedrine in
the core in combination with a rapid release HI aintagonist in ah external coat. The
disclosed osmotic device comprises of: a) a compressed core comprising of
pseudoephedrine, an osmotic agent, and optionally polyvinylpyrrolidone) for controlled
and continuous release of the drug; b) a semipermeable membrane, preferably consisting
essentially of cellulose esters, more preferably cellulose acetate esters, and poly(ethylene
glycol), surrounding the core and having a preformed passageway therein, said wall being
permeable to a fluid in the environment of use and substantially impermeable to the
pseudoephedrine; c) an inert water soluble polymer coat comprising poly
(vinylpyrrolidone)-(vinyl acetate) copolymer partially or substantially completely
surrounding the semipermeable membrane and plugging the passageway in the wall; and
d) an external coat comprising, optionally polyvinylpyrrolidone) and poly(ethylene
glycol), and an antihistamine for immediate release of the drug.
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In a very recently published application, WO 2006/048699 of Gaur et. al. an oral solid pharmaceutical composition comprising of two distinctive layers of which one layer comprises of a therapeutically effective amount of a piperidinoalkanol compound or a pharmaceutically acceptable salt thereof, with at least one functional excipient preferably diluents is disclosed. The other layer comprises of therapeutically effective amount of decongestant such as pseudoephedrine and its salts and derivatives thereof along with suitable excipients in an extended release form that releases the drug over specified period of time and a suitable process of manufacturing the same.
In yet another recently published application of Talasila et. al. US 2006/0182800, a pharmaceutical composition of antihistamine-decongestant combination is disclosed. The disclosed bi-layer tablet formulation comprises of a layer containing antihistaminic drug along with cellulose, mannitol, starch and croscarmellose sodium and another layer comprising a decongestant drug and a mixture of polyvinyl acetate and povidone.
Similarly, Ortyl et. al. in various applications such as US 5,855,912; US 6,113,942; US 5,738,872, and US 5,932,247 provides a formulation in solid Unit dosage form of antihistamines, namely fexofenadine, prepared by wet granulation process and having at least one inert ingredient selected from diluents, binders, disintegrants, lubricants, glidants and other well known pharmaceutically acceptable excipients. Diluents are selected from calcium carbonate, lactose, search, and microcrystalline cellulose; binders are selected from gelatin, polyvinylpyrrolidone (PVP), pregelatinized starch, povidone, cellulose derivatives including methyl cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), sucrose and the like; lubricants are from magnesium stearate, calcium stearate, zinc stearate, stearic acid, talc, hydrogenated vegetable oil and the like; glidants is selected from silicon dioxide, talc and the like; whereas disintegrants are selected from alginic acid, methacrylic acid, cross-linked PVP, microcrystalline cellulose, Croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, starch, | pregelatinized starch and the like. The above inert ingredients can be present in amounts up to about 95% of the total composition weight.
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Domet et. al. in US 4,929,605 describes a pharmaceutical composition of
piperidinoalkanol compounds only in solid unit dosage form comprising (a) a
therapeutically effective amount of a piperidinoalkanol compound, (b) pharmaceutically
acceptable nonionic or cationic surfactant in an amount of from about 0.1% to about 6%
by weight of the composition and (c) pharmaceutically acceptable; carbonate salt in an
amount of from about 2% to about 50% by weight of the composition. The said
composition is manufactured using wet granulation technique. '
From prior art discussed above, it will be abundantly evident that a large number of efforts have been done to design a pharmaceutical composition for the combination product of decongestant and a piperidinoalkanol aatihistaminic agent in the last two decades. Most of the above disclosed approaches focus on formulating a tablet having
two discrete zones, namely a zone of antihistamine and a zone of decongestant. Such an
t
approach would normally yield a bi-layer tablet formulation and even further, it is not necessary to mention that for preparation of such a formulation two separate granulation events and/or direct compression events are required during the tableting process.

However, the above discussed antihistamines are normally difficult to formulate because
of their sensitivity issues with compression. Further, these piperdinpalkanol derivatives
are normally minimally soluble in water and thereby aggravate the formulation
difficulties. In general, the poor water solubility limits the choice of tableting process to
either dry granulation or direct compression- Moreover, while preparing formulation of
such poorly water soluble active agents, an' utmost care needs to be given to select the
proper excipients. The excipients and manufacturing process can have an impact on
bioavailability of the drug. Therefore, judicious selection of excipients is must while
designing the formulation to ensure correct drug release in the blood stream. The
improper selection of the excipients further could also lead to cracking and unacceptable
physical strength of tablets on final compression.

Moreover, to prepare a bi-layer tablet as discussed above, the active agent and the various
excipients are often subjected to rigorous, mechanical operations s such as blending,
milling, granulation etc. Because of excessiye involvement of these processes, which are
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critical for formulation, certain ingredients may be found incompatible because of
particle size, particle density, flow characteristics, compressibility land moisture content

problems.

The osmotic drug delivery systems require very specialized and expensive manufacturing
process and equipment. Due to cost and- complexity involved in such drug" delivery systems, such an approach is largely of ah academic interest only and not particularly
viable from commercial point of view.

Thus, despite the availability of different compositions, there is a need for simple, stable and better preparations that are manufactured by an expedient manufacturing process.
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OBJECTS OF THE INVENTIONS
It is an object of the present invention to provide a novel and stable oral pharmaceutical
composition for the combination of a decongestant and a piperidinoalkanol antihistaminic
agent.
Another object of the present invention is to provide a novel and stable pharmaceutical composition for the combination of Pseudoephedrine or its salts and fexofenadine or its
salts.

Still another object of the present invention is to provide a. novel and stable
pharmaceutical composition for the combination of Pseudoephedrine or its salts and
fexofenadine or its salts wherein the release of Pseudoephedrine is controlled whereas the
release of fexofenadine is in immediate manner.
A further object of the present invention is to provide a process for preparation of novel
and stable pharmaceutical composition for the combination of a decongestant drug and a
I piperidinoalkanol antihistaminic agent.
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SUMMARY OF THE INVENTION
In order to achieve the abovementioned objectives, the present inventors have found that
a novel and stable oral pharmaceutical composition for the combination of antihistamine
drug and a decongestant drug could be made a simple process.
The invention herein is directed in one aspect to a pharmaceutical composition
comprising a core consisting of a therapeutically effective amount of a decongestant
agent and a mantle coating consisting of an antihistaminic agent surrounding the said
core.
Another embodiment of the present invention is a pharmaceutical composition wherein
an intermediate coating is provided which is a functional coating and surrounds the core but lies underneath the mantle coating consisting of antihistaminic agent. Such a functional coating provides a controlled release of the decongestant drug.
A preferred pharmaceutical composition herein has a structure wherein the core
comprises of the decongestant, preferably Pseudoephedrine hydrochloride in a
therapeutically effective amount and a mantle coating surrounding the core comprising
the antihistaminic agent, preferably fexofenadine hydrochloride in a therapeutically
effective amount.
Another embodiment of the present invention is a pharmaceutical composition including
a decongestant core, a basecoat of hydroxypropyl methylcellulose (HPMC) on the core
surface, a functional coat controlling the release of decongestant, a mantle coating of an
antihistaminic agent on the functional coat, and a topcoat |of hydroxypropyl
methylcellulose on the said antihistaminic agent coat.
DESCRIPTION OF THE INVENTION
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The invention herein is directed to an oral pharmaceutical composition comprising of a core of decongestant drug and surrounding the core is a mantle coating of piperidinoalkanol antihistaminic agent.
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In the preferred embodiment, the present invention provides an' oral pharmaceutical composition comprising of a core of decongestant drug and surrounding the core is a mantle coating of piperidinoalkanol antihistaminic agent and has a functional coating, which surrounds the core but lies underneath the mantle coating consisting of antihistaminic agent.
In the context of the present invention, the term "decongestant" means a drug that shrinks
the swollen membranes in the nose and makes it easier to breath. Decongestants are
adrenaline like drugs. Examples of decongestant include, but not limited to,
pesudoephedrine, phenylephrine and phenylpropanolamines and pharmaceutically
acceptable slats, polymorphs thereof.
As used herein the terms "piperidinoalkanol antihistamine or piperidinoalkanol
antihistaminic agent" refers to the compounds and to pharmaceutically acceptable salts,
polymorphs thereof, which have piperdinoalkanol moiety and works by counteracting the
effects of histamine on a receptor site. Th© representative examples) of piperdinoalkanol
agents are described in US patent numbers 3,878,217; 4,254,129 and 4,285,957, which
are incorporated herein by reference.
The term "functional coating" as used herein indicates a coating that modifies and/or
controls the release of the decongestant from the core of tablet formulation, for example,
a sustained-release coating. Because of the functional coating the release of the active
agent is controlled or modified over a period of time. Controlled can mean, for example,
extended, sustained, delayed or pulsed-release at a particular time. Moreover, controlled
can mean that the release of the active agent is extended for longer time than that from an
immediate-release dosage form having same amount of active agent. ,
The present pharmaceutical composition consists of a core which can be manufactured using any conventional method and can have any geometric shape. The composition includes a core which is comprised of decongestant, preferably Pseudoephedrine, or the pharmaceutically acceptable salts of such decongestants. The core can be formulated by compressing the Pseudoephedrine in any suitable tableting equipment; using compression
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tableting techniques well known in the art. Further, the core could also be formulated by spraying or layering the active agent on inert solid support, such as sugar bead.
In the core, decongestant can be present in any therapeutically acceptable amount. For normal phaimaceutically acceptable dosing of Pseudoephedrine, in combination with fexofenadine hydrochloride, Pseudoephedrine hydrochloride is administered in a~ therapeutic dosing range using tablets containing from 120 mg to 240 mg per tablet. Various excipients can be combined with: the Pseudoephedrine in! the core as is well known in the pharmaceutical art. Excipients used are selected from those which do not exhibit a destabilizing effect on either the Pseudoephedrine core or on the overall pharmaceutical composition. Examples of excipients that can be employed include diluents/fillers, binders, disintegrant, lubricant, glidants, antiadherants, surfactants, water
soluble polymers and water insoluble polymers.

A combination of excipients may also be used. Such excipients are known to those skilled in the art, and thus, only few representative examples for each class of excipient are mentioned herein below:
Diluents for the formulations are inert substances that may be used as a vehicle for the active agent, optionally in conjunction with other excipients, as long as the resulting formulation meets the desired dissolution profile and/or is stable. Suitable diluents include, lactose-based materials such as lactose monohydrate, spray dried lactose; cellulosic materials such as microcrystalline cellulose; starches; including partially pregelatinized starch, pregelatinized starch, partially hydrolyzed starch, maize starch, potato starch, rice starch, wheat starch, and tapioca starch; sugar such as sucrose, dextrose, fructose, and the like; sugar alcohols such as mannitol, sorbitol, xylitol, and the like; saccharides polysaccharides such as maltodextrin and the like; dibasic calcium phosphate, calcium sulphate, and the combinations thereof.
Combination of two or more diluents can be used in the dosage formulations. When used, the total amount of diluents can be up to about 99 weight percent of the total weight of the Pseudoephedrine formulation; specifically about 01 to about 60 weight percent; more
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specifically about 05 to about 30 weight percent; and yet more specifically about 10 to
about 25 weight percent.
j Binders may be, for example, starch, sugars, gums, hydroxypropyl methyl cellulose,
hydroxyl propyl cellulose or the like. Certain traditional tablet diluents may also function
as a disintegrant (e.g. starch), while other materials provide superior results as a
disintegrant, for example, croscarmellose sodium, crospovidone, low-substituted
hydroxypropyl cellulose, sodium starch glycolate, alginates, and the like. The disintegrant
can be present in the formulations in an amount of about 0.01 to about 20 weight percent
of the total weight of the formulation.
A lubricant and/or glidant can also be used in the dosage formulations to aid in the processing of powder materials. Exemplary lubricants include calcium stearate, glycerol behenate, magnesium stearate, mineral oil, polyethylene glycol, sodium stearyl fumarate, stearic acid, talc, vegetable oil, zinc stearate, and combinations thereof.
Other optional additives to the dosage formulations include, for example, sweetening agent, flavoring agents, stabilizing agents, colorants, antioxidants and combinations comprising one or more of the foregoing additives.
The decongestant core according to the present invention consisting of Pseudoephedrine hydrochloride can be prepared by a process, which includes the steps of:
(a) blending Pseudoephedrine in one or more of its form and its pharmaceutically acceptable salts with one or more pharmaceutically acceptable excipients to form a blend;
(b) granulating the blend of step (a) with the help of a suitable granulating agent;
(c) drying and milling the granules of step (b); and
(d) compressing the granules of step (c) to get a core.
The above disclosed process may further include any one of the features known to a person skilled in the art. For example, the process may further, optionally include granulating the blend of step (a) by a wet granulation process or by a dry granulation
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process and further, the active pharmaceutical ingredients and suitable excipients may be agglomerated in the beads called as 'pellets' by process of pelletization such as bailing, extrusion-spheronization, high-speed shear mixing.
The dosage formulation may comprise the active agent and excipients in the form of
particles having a particle size distribution that allows for the ease of processing" the
material, for example into core, by suitable techniques, without segregation of the
excipients. The desired particle size range of active agent and excipients and other
components may be obtained by processes known in the art, including granulating,
screening, milling, and the like.
Decongestant core, obtained by the process as disclosed above, are preferably further coated with a functional or release controlling coat. The functional coating is applied in such a way that the active agent is released at a substantially constant rate over a designated time period. Preferably, the controlled-release coating is capable of releasing the active agent at a substantially constant rate over a designated time period of from about 6, 8, 12, 24 and 48 hours. More preferably the designated time period is about 24 hours.
The functional coating can be of any agent well known in the art and used to control the release of active agent. Suitable examples of such agents include, but not limited to, hydroxypropyl methylcellulose ("HPMC"), hydroxypropyl methylcellulose phthalate ("HPMCP"), ethyl cellulose (EC), hydroxyethyl cellulose ("HEC"), hydroxy propyl cellulose ("HPC"), carboxy methyl cellulose ("CMC"), a methacrylic acid copolymer, cellulose acetate phthalate or mixtures thereof. The preferred controlled-release agent is ethyl cellulose, especially Surelease®.
Generally, when a controlled release coating agent is used, it may be used in an amount of about 30 percent by weight or less of the weight of the tablet core; specifically about 20 percent or less; and more specifically about 10 weight percent or less. In the preferred embodiment, the amount of controlled release coating material should not be so great that
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the coating material impedes the desired release profile of the active; agent when ingested
or evaluated for dissolution profile. I
A mantle coating of piperidinoalkanol antihistaminic agent surrounds the functional
coated core of Pseudoephedrine. When fexofenadine hydrochloride is used as
antihistaminic agent, it is present in an amount from about 50 to about 200 mg and
preferably from about 60 to 180 mg. The antihistaminic agent can be layered or coated on
the functional coated core with the help of any known coating] process in the art.
Processes such as simple or complex coacervation, interfacial polymerization, liquid
drying, thermal and ionic gelation, spray drying, spray chilling, fluidized bed coating, pan
coating, electrostatic deposition, may be Used. A substantially continuous nature of the
coating may be achieved, for example, by applying a coating solution to a moving bed of
core of the tablets with concurrent use of heated air to facilitate evaporation of solvent,
wherein the distribution of coating is accomplished by the movement of the tablets either
perpendicular or vertical to the application of coaling composition. Normally, in the
coating solutions, coating agent, suspending agent, plasticizing agent, anticaking agent,
disintegrant, colorants, sweeteners, flavoring agent could be present along with the active
agent. The selection of the excipient is governed by the fact, the release of antihistamine
from the mantle layer should not be hampered.
Suitable coating and or suspending agent include, but are not limited to cellulosic materials such as naturally occurring cellulose and synthetic cellulose derivatives such as hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxy ethyl cellulose, hydroxybutyl methyl cellulose, cellulose acetate, cellulose propionate, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, carboxymethyl cellulose (CMC), sodium CMC, cellulose triacetate, cellulose sulphate sodium salt, and the like; acrylic polymers and vinyl polymers, for example polymethyl methacrylate, poly ethyl methacrylate, poly butyl methacrylate, poly isobutyl methacrylate, poly hexyl methacrylate, poly phenyl methacrylate, poly methyl acrylate, poly isopropyl acrylate, poly isobutyl acrylate, poly octadecyl acrylate, poly ethylene, poly ethylene low density poly ethylene, high density poly propylene, poly
ethylene glycol, poly ethylene oxide, poly ethylene terephthalate, polyvinyl alcohol,
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polyvinyl isobutyl ether, polyvinyl acetate, poly vinyl chloride, polyvinyl pyrrolidone,
and the like; proteinaceous materials such as gelatin, polypeptides and natural and
synthetic shellacs and waxes; and combinations of the forgoing. Polyethylene glycols are
preferred as plasticizing agent. It is preferable to have combinations of polyvinyl
pyrrolidone and hydroxypropyl methyl cellulose. The preferred ratio of such
combinations ranges from about 1:2 to 2:1.
When a solvent is used to apply the fexofenadine coating, the solvent is preferably an
organic solvent. The solvent may be selected from alcohols such as methanol, ethanol,
isopropyl alcohol; halogenated hydrocarbons such as dichloromethane; cyclohexane, and
combinations comprising one or more of the foregoing solvents.
In still another embodiment of the present invention, the pharmaceutical composition
consists of an inner core comprising a decongestant or its salt as disclosed hereinbefore
with regard to the core. Surrounding the core is basecoat which can provide a surface for
the functional coat as basecoat can have a greater affinity for the functional coat than the
core alone. The basecoat can be of any suitable coating material and preferably is HPMC
in an amount about 1 to 5 percent by weight of the core.
In still preferred embodiment of the invention, a second basecoat is used to separate the
functional coat and the piperidinoalkanol antihistaminic agent coat. The second basecoat
can be of any suitable coating material and preferably is HPMC in an [amount about 1 to 5
percent by weight of the core. The second base coat is applied so as to achieve a uniform
coating of piperidinoalkanol antihistaminic agent onto functionally coated decongestant
core without changing the release properties of the decongestant core.|
A topcoat can then be applied over the piperidinoalkanol coat. The topcoat can be of any suitable material, preferably the topcoat is of HPMC, and in an amount about one to five percent by total weight of the composition.
Modifications of coating solutions discussed hereinbefore could be performed to improve adhesion of the coating to the core/underneath layer, to decrease bridging of intagliations, to increase coating hardness, or to improve or impart any desirable property. Typical
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examples of such modifications include changes to the polymer to plasticizer ratio, addition of different plasticizer or polymers, use of different colorant and opaquant in varying concentrations. Further, any suitable methods can be used to apply these coating solutions to the core or underneath layer.
The composition that is the invention herein is especially utile as the composition herein
exhibits a good stability for decongestant as well as antilustaminic component. A
particularly beneficial aspect of the invention herein is that the combination of the two
components in a core/mantle tablet assures compliance with the therapeutic regimen of
the two active agents. With the help of the present invention the release of the decongest
component can be controlled over a desired period of time, preferably for 24 hrs where as
the release of the antihistaminic component id not at all hampered is immediately
released in gastrointestinal environment.
The principles, preferred embodiments, and modes of operation of the present invention
have been described in the foregoing specification. The invention which is intended to be
protected herein, however, is not to be construed limited to the particular forms disclosed,
since these are to be regarded as illustrative rather than restrictive. Variations and
changes may be made by those skilled in the art, without departing from the spirit of the
invention.
The invention is further explained with the help of following illustrative examples, however, in no way these examples should be construed as limiting the scope of the invention. Tablets of different strengths and doses, as known in the art, can be prepared by varying the quantities of excipients, proportionately, with respect to the amount of active ingredient. Hence any embodiment that may be apparent to a person skilled in the art, with respect to the following example is deemed to fall within the scope of the present invention.
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EXAMPLES

Example -1
A pharmaceutical tablet formulation was prepared consisting of a Pseudoephedrine hydrochloride central core, a base coat applied on said core and then a fexofenadine hydrochloride mantle. The tablet had the following composition:
Quantity (mg/tablet) Core
240
51
56.75
5.75
3.5
3.0
q.s.
10.8 q.s.
180
7.20
10.80
118.0
25.20
0.01
q.s.
q.s.
Pseudoephedrine hydrochloride
Ethyl cellulose
Lactose
Hydroxy propyl methyl cellulose
Magnesium stearate
Colloidal silicon dioxide
Purified water
Base Coat
Opadry YS-1-7006 clear Purified water
Mantle
Fexofenadine hydrochloride
Copovidone
Hydroxypropyl methyl cellulose
Croscarmellose sodium
Talc
PEG 6000
Isopropyl alcohol
Methylene chloride

Example - 2
A pharmaceutical tablet formulation was prepared consisting of a Pseudoephedrine hydrochloride central core, a functional coat applied on said core and then a fexofenadine hydrochloride mantle. The tablet had the following composition:
Quantity (mg/tablet)
Core
240
45
100
3.5
3.0
q.s.
Pseudoephedrine hydrochloride Polyvinyl acetate Ethyl cellulose Magnesium stearate Colloidal silicon dioxide Purified water
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Functional Coat
Ethyl cellulose 3
Hydroxypropyl methyl cellulose 1.5
Triacetin 0.75
Isopropyl alcohol 85
Purified water q.s
Mantle
Fexofenadine hydrochloride 180
Copovidone 6.00
Hydroxypropyl methyl cellulose 9.00
Croscarmellose sodium 50.00
Talc 10.50
Isopropyl alcohol q.s.
Methylene chloride q.s.
Example - 3

A pharmaceutical tablet formulation was prepared consisting of a Pseudoephedrine
hydrochloride central core, a functional coat applied on said core and then a fexofenadine
hydrochloride mantle. The tablet had the following composition:
Quantity (mg/tablet)
Core
Pseudoephedrine hydrochloride 240
Polyvinyl acetate 45
Ethyl cellulose 100
Magnesium stearate 3.5
Colloidal silicon dioxide 3.0
Purified water q.s.
Functional Coat
Ethyl cellulose 3
Hydroxypropyl methyl cellulose 1.5
Triacetin 0.75
Isopropyl alcohol 85
Purified water q.s
Mantle
Fexofenadine hydrochloride 180
Copovidone 7.20
Hydroxypropyl methyl cellulose 10.80
Croscarmellose sodium 90.00
Pregelatinized starch 28.00
PEG 6000 0.01
Talc 25.20
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Isopropyl alcohol Methylene chloride

q.s. q.s.

Example - 4
A pharmaceutical tablet formulation was prepared consisting of a Pseudoephedrine hydrochloride central core, a base coat and then a functional coat applied on said core and a fexofenadine hydrochloride mantle. The tablet had the following composition:
Quantity (mg/tablet)
Core I
Pseudoephedrine hydrochloride 240
Ethyl cellulose 51
Lactose 56.75
Hydroxy propyl methyl cellulose 5.75
Magnesium stearate 3.5
Colloidal silicon dioxide 3.0
Purified water q.s.
Base Coat
Opadry YS-1-7006 clear 10.8
Purified water q.s.
Functional Coat
Surelease 163.12
Hydroxypropyl methyl cellulose 10.195
Purified water q.s.
Mantle
Fexofenadine hydrochloride 180
Copovidone 7.20
Hydroxypropyl methyl cellulose 10.80
Croscarmellose sodium 118.0
Talc 25.20
PEG 6000 0.01
Isopropyl alcohol q.s.
Methylene chloride q.s.

Example - 5
A pharmaceuticals tablet formulation was prepared consisting of a Pseudoephedrine
hydrochloride central core, a base coat and then a functional coat applied on said core and then a fexofenadine hydrochloride mantle. The tablet had the following composition:
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Example - 6
A pharmaceutical tablet formulation was prepared consisting of a
hydrochloride central core, a base coat and then a functional coat app]
a fexofenadine hydrochloride mantle. The said tablet then is further coated with a top
coat. The tablet had the following composition:

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Base Coat
Opadry YS-1-7006 clear 10.8
Purified water q.s.
Functional Coat
Surelease 88.99
Hydroxypropyl methyl cellulose 5.562
Purified water q.s.
Mantle
Fexofenadine hydrochloride 180
Copovidone 7.20
Hydroxypropyl methyl cellulose 10.80
Croscarmellose sodium 90.0
Talc 30.6
Pregelatinized starch 28
Isopropyl alcohol q.s.
Methylene chloride q.s.
Example - 7
Drug release profile of the two drugs from batches produced in Example -5 and 6 were performed using standard USP test. Similarly the release profile of the two drugs from a commercially available preparation sold under the brand name of Allegra D (24 hrs.) are compared. The results of this study are summarized in Table-1.
Table -1: Comparative release profile of the pharmaceutical composition according to present invention with a commercially available formulation

Time (Hours) Innovator Allegra D (24 Hrs) Example 6 (6% functional coated) Example 5 (12% functional coated)
% Pseudoep hedrine Release
1 1.2 0.5 1.9
2 7.8 5.8 4.7
4 21.5 33.1 14.0
6 34.2 55.4 29.4
8 46.6 71.0 44.0
10 57.8 82.2 56.9
12 67.3 88.6 67.5
20

16 78.8 96.0 82.9
20 84.0 99.1 92.2
24 87.0 100.9 98.4
% Fexofenadine Release
Time (Min)
5 - 20.9 ND
10 51.9 67.9 ND
20 77.7 82.8 ND
30 82.5 84.9 ND
45 84.3 84.7 ND
60 85.2 85.0 ND
ND - not determined
21

We claim:
1. A pharmaceutical tablet composition comprising:

a. a core consisting of a therapeutically effective amount of a decongestant; and
b. a mantle coating surrounding the said core comprising a therapeutically
effective amount of a piperidinoalkanol antihistaminic agent.

2. A pharmaceutical composition according to claim -1, wherein the decongestant is s there of pseudoephedrine or pharmaceutically acceptable salts, polymorph

3. A pharmaceutical composition according to claim piperidinoalkanol antihistaminic agent is fexofenadine acceptable salts, polymorphs thereof.

-1, wherein the or pharmaceutically

4. A pharmaceutical composition according to claim -1, further comprising of an intermediate functional coating surrounding the core.
5. A pharmaceutical composition according to claim -4, wherein the functional coating controls the release of the decongestant from the core of the tablet for a period of about 6 hrs to about 48 hrs.
6. A pharmaceutical composition according to claim -5, wherein the release of decongestant from the core is controlled for a period of 24 hrs.
7. A pharmaceutical composition according to claim -1, wherein the core comprises of Pseudoephedrine hydrochloride in an amount ranging from about 120 mg to about 240 mg and the mantle coating comprises of fexofenadine hydrochloride in an amount ranging from about 60 mg to about 180 mg.
8. A pharmaceutical composition according to claim -1, wherein the mantle coating comprises of hydroxypropyl methyl cellulose and vinyl pyrrolidone- vinyl acetate copolymer.
22

9. A pharmaceutical composition according to claim -8, wherein the mantle coating comprises of copovidone and hydroxypropyl methyl cellulose in a ratio ranging from about 1: 2 to 2:1. '
10. A pharmaceutical tablet composition comprising:
a. a core consisting of a therapeutically effective amount of pseudoephedrine
hydrochloride;
b. first base coat;
c. a functional coat;
d. second base coat
e. a mantle coating surrounding the said functional coat comprising a
therapeutically effective amount of fexofenadine hydrochloride; and
f. a top coat of cellulosic coating material.
11. A process for preparation of a pharmaceutical tablet composition of a
decongestant and a piperidinoalkanol antihistaminic agent comprising the steps
of:
a. Preparation of a core comprising decongestant;
b. optionally, applying a base coat on the said core;
c. optionally, applying a functional coat on the said core;
d. applying a mantle coat comprising of piperidinoalkanol antihistaminic agent.
12. Process for preparation of a solid oral dosage formulation of decongestant and
piperidinoalkanol antihistaminic agent as described herein with the help of
foregoing Examples. '

23

Abstract
A PHARMACEUTICAL COMPOSTION
A pharmaceutical composition comprising a core of decongestant and a piperidinoalkanol mantle coating is provided. Various intermediate coating can be present between the decongestant core and piperidinoalkanol mantle coating. The pharmaceutical composition can provide a controlled release of decongestant for 48 hrs and immediate release of the piperidinoalkanol antihistaminic agent.