COMPLETE SPECIFICATION
Field of the Invention
The Present invention relates to the novel and synergistic pharmaceutical composition comprising [7(s)-(1a,2ß,4ß,5α,7ß)]-9-butyl-7-(3-hydroxy- 1-oxo-2-phenylpropoxy)-9-methyl-3-oxa-9-azonitricyclo[3.3.1.0(2,4)]nonane or the pharmaceutically accepted salts and 2-(2,3-dimethylphenyl) aminobenzoic acid. The above combination is used to relief from the discomfort and pain of stronger abdominal cramps and menstrual pain. Further, the invention relates to a formulation having higher absorption of 2-(2, 3-dimethylphenyl) amino benzoic acid.
Prior Art Related to the invention
Application number GB1425969 pharmaceutical compositions for treating psychomotor disorders, neuroses, vegetative dystonias &c comprise (a) a benzodiazepine tranquilizer e.g. chlordiazepoxide, Diazepam or Oxazepam; (b) ergotamine and/or dihydroergocristine and/or a salt thereof, and (c) a Belladona alkaloid or a synthetic or semisynthetic analogue thereof e.g. atropine, hyoscyamine or scopolamine, or N-ethylnortropine benzhydryl ether. The compositions may be administered orally in the form of tablets, dragees, capsules, elixirs and syrups.
RU 2220713 relates to analgetic, spasmolytic, anti-inflammatory medicinal agent. Proposed medicinal agent represents pharmaceutical composition comprising spasmolytic component and/or at least one non-narcotic analgetic agent taken among the group: paracetamol, ketorolac, propifenone, purine alkaloid; sedative component-barbiturate taken among the group: phenobarbital, pentobarbital, cyclobarbital; and at least one compound taken among nonsteroid anti-inflammatory agents:

naproxen, sulindac, mefenamic acid, niflumic acid, diflunisal, sodium salicylate, salicylamide, butadion, lornoxicam or its mixture with agonist of opioid receptors. Invention provides arresting pain being any etiology practically: 1) pain in the presence of inflammatory component; 2) spasm-associated pain; 3) pain associated with neurological process. Proposed preparation shows attenuated adverse effects, such as dyspeptic symptoms, vertigo, epigastric pains.
Objectives of the Invention
The objective of the formulation is to provide the novel synergistic combination to treat pain.
Yet another object of the formulation is to provide a combination having fewer side effects.
Yet another object of the formulation is to provide the immediate relief from menstrual pain and muscular spasm.
Yet another object of the invention is to reduce the side effects of 2-(2, 3-dimethylphenyl) amino benzoic acid by increasing the absorption.
Yet another objection of the invention is to provide a complete combination for treating the pain and cramps associated with gastric disorders and acidity.
Detailed Description of the Invention
[7(s)-(1α,2ß,4ß,5α,7ß)]-9-butyl-7-(3-hydroxy- 1-oxo-2-phenyl propoxy)-9-methyl-3-oxa-9-azonitricyclo[3.3.1.0(2,4)] nonane is a peripherally acting antimuscarinic, anticholinergic agent used as an abdominal-specific antispasmodic. It is a quaternary ammonium compound and a semisynthetic derivative of scopolamine. It is used to treat pain and discomfort caused by

abdominal cramps, menstrual cramps, or other spasmodic activity in the digestive system.
2-(2, 3-dimethylphenyl) amino benzoic acid is a non-steroidal anti-inflammatory drug used to treat pain, including menstrual pain. It is typically prescribed for oral administration.
2-(2, 3-dimethylphenyl) amino benzoic acid decreases inflammation (swelling) and uterine contractions by a still unknown mechanism. However it is thought to be related to the inhibition of prostaglandin synthesis. There is also evidence that supports the use of 2-(2,3-dimethylphenyl) amino benzoic acid for perimenstrual migraine headache prophylaxis, with treatment starting 2 days prior to the onset of flow or 1 day prior to the expected onset of the headache and continuing for the duration of menstruation.
2-(2, 3-dimethylphenyl) amino benzoic acid is known to cause an upset stomach, therefore it is recommended to take prescribed doses together with food or milk. Instances of drowsiness may also occur. Other known mild side effects of 2-(2,3-dimethylphenyl) amino benzoic acid include headaches, nervousness and vomiting. Serious side effects may include diarrhea, hematemesis (vomiting blood), haematuria (blood in urine), blurred vision, skin rash, itching and swelling, sore throat and fever.
It was surprisingly found out that the side effects of 2-(2,3-dimethylphenyl) amino benzoic acid can be reduced by increasing its absorption and by reducing the residing time of the drug in the stomach.
Thus various attempts are made to find the way so as to increase the absorption of 2-(2, 3-dimethylphenyl) amino benzoic acid.

It was found that if - (2, 3-dimethylphenyl) amino benzoic acid is administered with magnesium hydroxide the rate and extent of absorption increases.
Thus the present invention relates to a synergistic composition comprising [7(s)-(1α,2ß,4ß,5α,7ß)]-9-butyl-7-(3-hydroxy- 1-oxo-2-phenylpropoxy)-9-methyl-3-oxa-9-
azonitricyclo[3.3.1.0(2,4)]nonane or the pharmaceutically accepted salts and 2-(2,3-dimethylphenyl) amino benzoic acid with increased bioavailability, so as to lower the side effects of the combination.
The 2-(2,3-dimethylphenyl) amino benzoic acid used in the formulation is in the range of 100mg to 600mg, preferably 150mg to 500mg, more preferably 200 mg to 300 mg.
The [7(s)-(1α,2ß,4ß,5α,7ß)]-9-butyl-7-(3-hydroxy- 1-oxo-2-phenylpropoxy)-9-methyl-3-oxa-9-
azonitricyclo[3.3.1.0(2,4)]nonane used in the present formulation is in the range of 5 mg to 20 mg, preferably 7mg to 15mg,.
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 both the active ingredients from the pharmaceutical formulations of the present invention can be immediate or modified, controlled, delayed, sustained, and extended. The release rate for both active drugs can be the same or different.
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 both the active ingredients.
The said invention can be formulated, but not limited to, in the following manner- (Table Removed)

CLAIMS
1) A pharmaceutical formulation comprises of:-
a) 2-(2,3-dimethylphenyl) amino benzoic acid or its
pharmaceutically acceptable salts,
b) [7(s)-(1α, 2ß, 4ß, 5α, 7ß)]-9-butyl-7-(3-hydroxy- 1-oxo-2-phenylpropoxy)-9-methyl-3-oxa-9-azonitricyclo [3.3.1.0(2, 4)] nonane or its pharmaceutically acceptable salts,
c) Absorption enhancer for 2-(2, 3-dimethylphenyl) amino benzoic acid,
d) Pharmaceutically acceptable excipients.

2) Pharmaceutical formulation as claimed in claim 1 may be in the form of tablet, capsule or syrup.
3) The 2-(2,3-dimethylphenyl) amino benzoic acid as claimed in claim 1 is in the range of 100mg to 600mg, preferably 150mg to 500mg, more preferably 200 mg to 300 mg, whereas [7(s)-(1α,2ß,4ß,5α,7ß)]-9-butyl-7-(3-hydroxy-l-oxo-2-phenylpropoxy)-9-methyl-3-oxa-9-azonitricyclo[3.3.1.0(2,4)] nonane as claimed in claim 1 is in the range of 5 mg to 20 mg, preferably 7mg to 15mg,.
4) Absorption enhancer as claimed in claim 1 may be magnesium hydroxide.
5) The pharmaceutically acceptable excipients as claimed in claim 1 are selected from diluents, binding agents, disintegrants, and lubricants.
6) The diluents as claimed in claim 5 can be selected from lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate.
7) The binding agents as claimed in claim 5 can be selected from polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), xylitol, sorbitol and maltitol which are mixed with the appropriate solvent.
8) The solvent as claimed in claim 7 can be selected from purified water or isopropyl alcohol or the mixture of both.

9) The disintegrants as claimed in claim 5 can be selected from
polyvinylpyrrolidone (crospovidone), crosslinked sodium
carboxymethyl cellulose (croscarmellose sodium), starch, micro
crystalline cellulose and sodium starch glycolate.
10) The lubricants as claimed in claim 5 can be selected from talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid.