DESCRIPTION
FIELD OF THE INVENTION
The present invention is related to a novel and stable pharmaceutical formulation
comprising anti-inflammatory, antipyretic having lesser side effects. The side
effects of anti-inflammatory drugs are reduced by the addition of H+/K+ ATPase
inhibitor.
PRIOR ART OF THE INVENTION
AU 2005/213472 is related to pharmaceutical compositions comprising a proton
pump inhibitor, a buffering agent, and a non-steroidal anti-inflammatory drug.
Methods for manufacture of the pharmaceutical compositions and use of the
pharmaceutical compositions in treating disease are disclosed.
WO 2007/129178 relates to pharmaceutical compositions in the form of fixed
combination comprising non-steroidal anti-inflammatory drug or its single
enantiomers or salts thereof, antipyretic-analgesic drug and proton pump inhibitor
or its single enantiomers or salts thereof. The invention also relates to processes
for the preparation of such compositions.
US Patent No. 6,926,907 disclose pharmaceutical composition in unit dose form
for oral administration comprising an acid inhibitor present in an amount effective
to raise the gastric pH to at least 3.5 upon the administration of one or more of said
unit dosage forms; and a non-steroidal anti-inflammatory drug (NSAID) in an
amount effective to reduce or eliminate pain or inflammation upon administration of
one or more of said unit dosage forms.
The above prior arts have the following drawbacks-
The formulation obtained as described from some of the above prior art were not
stable. The proton pump inhibitor degrades and changes to black from white
thereby reducing the potency of the drug.
Further in the above prior art, no method was described to avoid the degradation of
the formulation.
Also there was no specific coating done on the tablets, in the prior art, that protects
the tablets from degradation thereby maintaining its potency.
Thus there exists a need for a formulation with lesser side effects as well as stable
thus imparting the required therapeutic potency.

OBJECTIVES OF THE INVENTION
The object of the present invention is to provide a stable formulation which does not gets deteriorated.
Yet another object of the invention is to provide a formulation of Aceclofenac and paracetamol with fewer side effects.
Yet another object of the invention is to provide a formulation that will be able to deliver the therapeutically effective dose. SUMMARY OF THE INVENTION
The present invention is related to a novel and stable pharmaceutical formulation comprising anti-inflammatory, antipyretic having lesser side effects. The side effects of anti-inflammatory drugs are reduced by the addition of H+/K+ ATPase inhibitor. The anti-inflammatory is preferably aceclofenac, antipyretic is preferably paracetamol and the H+/K+ ATPase inhibitor is preferably rabeprazole.
DETAILED DESCRIPTION OF THE INVENTION
NSAIDs are regularly used by millions of people for the treatment of musculoskeletal pain. One major limitation of NSAID use is the risk of serious upper gastrointestinal events, including bleeding, perforation and obstruction. Although serious upper gastrointestinal events are uncommon, they remain a significant public health problem because of the vast number of patients who take NSAIDs.
Epidemiologic studies suggest that, for patients taking NSAIDs, the risk of ulcer complications increases approximately fourfold.
Aceclofenac relieves pain and inflammation through a variety of mechanisms and in addition exerts stimulatory effects on cartilage matrix synthesis. Anti¬inflammatory activity: The anti-inflammatory effects of Aceclofenac have been shown in both acute and chronic inflammation.
Paracetamol is a clinically proven analgesic and antipyretic agent with weak anti¬inflammatory effect.
Analgesic action: The central analgesic action of Paracetamol resembles that of aspirin. It produces analgesia by raising pain threshold.
Antipyretic effect: The antipyretic effect of Paracetamol is attributed to its ability to inhibit COX in the brain where peroxide tone is low. Recent evidence suggests inhibition-of COX-3 (believed to be splice variant product of the COX-1 gene) could

represent a primary central mechanism by which Paracetamol decreases pain and
possibly fever.
Rabeprazole sodium is a drug used to treat gastroesophageal reflux disease, or
GERD, which is a common digestive problem.
The present invention discloses the method of formulation of a stable triple drug
combination comprising aceclofenac, paracetamol and rabeprazole.
The formulation is prepared through tablet-in-tablet technology, in which a tablet of
rabeprazole is present inside the tablet of aceclofenac and paracetamol
formulation. The coating on the rabeprazole is done in such a manner that it
retains its potency. Furthermore, a coating is done on the whole formulation so that
the formulation becomes stable.
The novelty in the invention is the technology by which the said invention is
formulated. The technology incorporated in the formulation maintains the efficacy
and chemical stability for a longer period of time.
Aceclofenac or its pharmaceutically acceptable salt is present in the range of 50
mg to 200 mg, more preferably 100 mg. Paracetamol is present in the range 300
mg to 700 mg, more preferably 500 mg. Rabeprazole or its pharmaceutically
acceptable salt is present in the range 10 mg to 30 mg, more preferably 20 mg.
Suitable fillers may be microcrystalline cellulose, powdered cellulose, lactose,
starch, pregelatinized starch, or sucrose preferably microcrystalline cellulose and
lactose.
Suitable binders are starch, polyvinylpyrrolidone, alginic acid, methylcellulose,
hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose,
polymethacrylates, and others preferably hydroxypropyl cellulose, hydroxypropyl
methylcellulose and polyvinylpyrrolidone.
Suitable disintegrants are starch, pregelatinized starch, sodium starch glycolate,
sodium carboxymethylcellulose, cross-linked sodium carboxymethylcellulose,
cross-linked polyvinylpyrrolidone, alginic acid, sodium alginate, and others
preferably sodium starch glycolate, cross-linked sodium carboxymethylcellulose
and cross-linked polyvinylpyrrolidone.
Suitable glidants are magnesium stearate, calcium stearate, aluminium stearate,
stearic acid, palmitic acid, cetanol, stearol, colloidal silicon dioxide, talc, powdered
cellulose, starch and others, preferably, colloidal silicon dioxide."

Suitable lubricants are stearic acid, calcium, magnesium, zinc or aluminium
stearate, siliconized talc, glycerol monostearate, and others. Preferred lubricants
are calcium or magnesium stearate and stearic acid.
The release of Aceclofenac and Paracetamol with Rabeprazole from the
pharmaceutical formulations of the present invention can be immediate or
modified, controlled, delayed, sustained, and extended.
The pharmaceutical formulations of the present invention may comprise formed
particles with the same composition or formed particles with different composition and different release rate of Aceclofenac and Paracetamol with Rabeprazole.

.CLAIMS
1. A pharmaceutical formulation comprising Aceclofenac or its pharmaceutically acceptable salt in the range of 50 mg to 200 mg, more preferably 100 mg, Paracetamol in the range 300 mg to 700 mg, more preferably 500 mg and enteric coated Rabeprazole or its pharmaceutically acceptable salt in the range 10 mg to 30 mg, more preferably 20 mg with pharmaceutically acceptable excipients; wherein the said formulation is formulated with tablet-in-tablet technology.
2. The formulation, as claimed in claim 1, comprises a enteric coated tablet of rabeprazole incorporated in the tablet of Aceclofenac and Paracetamol, providing more stability to the formulation.
3. The pharmaceutically acceptable excipients claimed in 1 are selected from diluents, binding agents, disintegrants, and lubricants.
4. The diluents as claimed in claim 3 can be selected from lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate.
5. The binding agents as claimed in claim 3 can be selected from polyvinylpyrrolidone (PVP), Hydroxy propyl cellulose, polyethylene glycol (PEG), xylitol, sorbitol and maltitol which are mixed with the appropriate solvent.
6. The solvent as claimed in claim 5 can be selected from purified water or isopropyl alcohol or the mixture of both.
7. The disintegrants as claimed in claim 3 can be selected from polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose (croscarmellose sodium) and sodium starch glycolate.
8. The lubricants as claimed in claim 3 can be selected from talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid.
9. The formulation as claimed in claim 1 can be coated with Hydroxypropyl
Methyl Cellulose, along with suitable plasticizer, opacifier, coloring agent and the solvent.