FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)


1. TITLE OF THE INVENTION:
Stabilized pharmaceutical composition comprising Gabapentin with minimum levels of pharmaceutically acceptable inert excipients.
2. APPLICANT (S)
(a) NAME: Micro Labs Limited.
(b) NATIONALITY: Indian
(c) ADDRESS: CTS No. 73, Saki Estate, Off Chandivali Road, Chandivali,
Kurla (W), Mumbai - 400 072.
3. PREAMBLE TO THE DESCRIPTION
There is provided a stabilized pharmaceutical composition comprising Gabapentin with minimum levels of pharmaceutically acceptable inert excipients.
4. DESCRIPTION (Description shall start from the next page.)
The following specification particularly describes the invention and the manner in which it is to be performed.


Description
There is provided a stabilized pharmaceutical composition comprising Gabapentin with minimum levels of pharmaceutical acceptable inert excipients.
Gabapentin is an anticonvulsant that is used for preventing seizures and for treating post therapeutic neuralgia. It is described as 1-(amino methyl) cyclohexaneacetic acid with a molecular formula of C9H17NO2 and a molecular weight of 171.24. The structural formula of Gabapentin is:

Gabapentin is commercially available in different dosage forms like tablets, capsules and solution form.
PCT publication WO 01/13894 discloses a pharmaceutical tablet comprising more than about 76 % by weight of Gabapentin.
PCT publication WO 05/055993 discloses a Gabapentin granulate obtained by granulating Gabapentin with polyethylene glycol having a melting point comprised between 50 and 80°C and pharmaceutical compositions containing it.
PCT publication WO 05/072736 discloses a pharmaceutical composition of Gabapentin wherein lactum level remains below 0.5% w/w after at least 2 years of storage at 25°C and 60% relative humidity.
PCT publication WO 04/014356 discloses a solid pharmaceutical composition comprising Gabapentin, a basic compound that is a hydroxide or a salt of weak acid, and at least one other excipient that is not a hydroxide or a salt of a weak acid.


PCT publication WO 04/032905 discloses a solid pharmaceutical composition comprising Gabapentin using wet granulation method.
US patent 6,531,509 discloses pharmaceutical compositions containing substantially pure and stable Gabapentin wherein Gabapentin contains an anion of a mineral acid, such as chloride, in amounts greater than 20 ppm.
US 6,054,482 discloses a method of preparing Gabapentin which is free of Gabapentin lactam.
The recommended dose of Gabapentin for post therapeutic neuralgia is 1800 mg daily in 3 divided doses. The initial dose of 300 mg daily is increased over several days to the recommended daily dose. Seizures are treated with 900-1800 mg/daily in 3 divided doses. It is difficult to formulate Gabapentin composition because of its high dose. Further, it is not convenient for patient to consume formulation of a relatively larger size.
Gabapentin being the molecule with two functional group in the close vicinity has a tendency to make intramolecular lactam in presence of either much acidic or basic media. It is difficult to formulate Gabapentin because of formation of intramolecular lactam. This lactam is toxic. So it is undesirable to have this impurity in the pharmaceutical composition.
It was noticed by the inventors while working on the Gabapentin compositions that these problems can be avoided and thus, there is provided a stabilized pharmaceutical composition comprising Gabapentin with minimum levels of pharmaceutically acceptable inert excipients. Also, this composition is patient compliant.


In one aspect of the invention, there is provided a stabilized pharmaceutical composition comprising Gabapentin with minimum levels of pharmaceutically acceptable inert excipients.
The pharmaceutical composition may be a solid dosage form. The solid dosage form may be one or more of tablet, capsule, powder, disc, caplet, granules, pellets, granules in capsule, minitablets, minitablets in capsule, pellets in capsule, sachet and the like. The solid dosage form also includes multilayer tablets. The core as disclosed herein includes uncoated solid dosage form.
The minimum level of excipients as disclosed herein includes 0.1 to 10 % of the total weight of the core, more specifically 0.1 to 6% of the total weight of the core. The core may be one or more of tablet, powder, disc, caplet, granules, pellets and the like. Gabapentin being the molecule with two functional group in the close vicinity has a tendency to make intra molecular lactam in presence of either much acidic or basic media, thus absence of /or less excipient resulted in low impurity.
The pharmaceutical composition contains Gabapentin as active ingredient. The active ingredient may be present in the form of powder, granules, pellets, beads, microtablets, minitablets and crystals.
The term 'stabilized' as used herein means that the composition has content of lactam impurity below 0.2 % when subjected to the stability conditions of 40°C and 75% relative humidity for six months.
The pharmaceutical composition comprises one or more pharmaceutically acceptable inert excipients. The pharmaceutically acceptable inert excipients may be one or more of binders, disintegrants, lubricants, glidants, solvents and the like.


Suitable binder may be one or more of, povidone, starch, stearic acid, gums, hydroxypropylmethyl cellulose and the like.
Suitable disintegrant may be one or more of starch, croscarmellose sodium, crospovidone, sodium starch glycolate and the like.
Suttable solvent may be one or more of isopropy alcohol, methylene chloride water and the like.
Suitable lubricant may be one or more of magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate, hydrogenated vegetable oil, glyceryl behenate and the like.
Suitable glidant may be one or more of colloidal silicon dioxide, talc or cornstarch and the like.
The solid dosage form may optionally be film coated. The film coating may comprise one or more of film formers, solvents, plasticizers and the like.
Suitable film formers may be one or more of hydroxypropyl methyl cellulose, methyl hydroxyethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, povidone, sodium carboxymethyl cellulose, polyethylene glycol, acrylates and the like.
Suitable solvents may be one or more of water, ethanol, methanol, isopropanol, chloroform, acetone, methylethyl ketone, methylene chloride and the like.
Suitable plasticizers may be one or more of propylene glycol, castor oil, glycerin, polyethylene glycol, polysorbates, and the like.
In another aspect, there is provided a process for preparing a stabilized pharmaceutical composition comprising Gabapentin with minimum levels of


pharmaceutical^ acceptable inert excipients, the said process comprising coating or mixing Gabapentin with one or more pharmaceutical^ acceptable inert excipients.
The pharmaceutical composition may be prepared by processes those known to ordinary skill in the art and include but not limited to dry granulation, wet granulation and direct compression.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Example -I
Table-1: Pharmaceutical composition of the invention

Sr. No. Ingredients Quantity/unit in mg.
01 Gabapentin 800.0 600.0
02 Hydroxypropyl cellulose 25.0 18.75
03 Isopropyl alcohol / Methylene chloride q.s. q.s.
04 Low-Substituted Hydroxypropyl Cellulose 12.0 9.0
05 Magnesium Stearate 8.0 6.0
Average weight of core tablet 845.0 633.75
Coating
06 Opadry 25.00 18.75
07 Isopropyl alcohol / Methylene chloride q.s. q.s.
Average weight of film-coated tablet 870.0 652.5
Procedure:
1. Gabapentin was sifted.
2. Hydroxypropyl cellulose was dissolved in isopropyl alcohol or methylene chloride to form a solution.


3. Gabapentin in step 1 was granulated with solution in step 2 to form granules.
4. The granules in step 3 were dried.
5. The dried granules in step 4 were sifted and blended with Low-Substituted Hydroxypropyl Cellulose to from a blend.
6. The blend formed in step 5 was lubricated with Magnesium stearate.
7. The lubricated blend was compressed to form tablets.
8. The compressed tablets were film coated with opadry.
Stability data:
The packaged tablets of the above example were subjected to the stability studies of 40°C and 75% relative humidity for 6 months. Quantitative determination of lactam impurity in the composition was used as the stability indicating test. The results are as given in Table 2.
Table-2: Stability data of the pharmaceutical composition in example 1.

% of lactam impurity
Conditions 600 mg strength 800 mg strength

Initial 6 months Initial 6 months
Bulk pack Stability accelerated 0.018 0.070 0.02 0.092

Long term stability 0.018 0.031 0.02 0.037
Aluminium blister pack Stability accelerated 0.018 0.070 0.02 0.092

Long term stability 0.018 0.030 0.02 0.037


We claim:
1. A stabilized pharmaceutical composition comprising Gabapentin with minimum levels of pharmaceutical^ acceptable inert excipients.
2. The pharmaceutical composition according to claim 1, wherein the composition is in the form of solid dosage form.
3. The pharmaceutical composition according to claim 2, wherein the level of excipients is from 0.1 to 10 % of the core.
4. The pharmaceutical composition according to claim 2, wherein the level of excipients is from 0.1 to 6 % of the core.
5. The pharmaceutical composition according to claim 1, wherein the excipients are may be one or more of binders, disintegrants, lubricants, glidants, and solvents.
6. The pharmaceutical composition according to claim 1, wherein the composition is film coated.
7. The pharmaceutical composition according to claim 6, wherein the excipients may comprise one or more of film formers, solvents, plasticizers.
8. A process for preparing a stabilized pharmaceutical composition comprising Gabapentin with minimum levels of pharmaceutically acceptable inert excipients, the process comprising coating or mixing Gabapentin with one or more pharmaceutically acceptable inert excipients.


9. The process according to claim 6, wherein the process is dry granulation, wet granulation or direct compression.
10.A pharmaceutical composition as herein above described in the specification.