The present invention relates to sustained release oral dosage forms of gabapentin and a process for the preparation thereof
Gabapentin (l-(aminomethyl)cyclohexaneacetic acid) is an y-amino acid analogue effective in the treatment of epilepsy. Gabapentin is indicated as an adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults with epilepsy. Gabapentin has also been approved for neuropathic pain in some of the countries.
Some epileptic patients need to take medication throughout their lives while others may only require it for a limited period. The importance of taking dmgs at regular intervals cannot be overemphasized. However, it is not easy for everyone to remember to take the correct dose at the same time each day. Multiple dosing is not only inconvenient but also lowers patient compliance.
Gabapentin has a relatively short half-life (5-7hours), which leads to substantial fluctuations in the plasma concentration of the drug. Frequent dosing is necessary to maintain reasonably stable plasma concentrations. The effective dose of gabapentin is 900 to 1800 mg/day, which is given, in divided doses. Gabapentin conventional dosage forms like tablets or capsules are administered three times a day. This mode of therapy leads to sudden high drug concentration in the blood after dosing, and then a rapid decrease in drug concentrations as a result of drug distribution, metabolism and elimination. The high difference in minimum and maximum plasma concentration is a major disadvantage associated with conventional dosage forms. A sustained release dosage form of gabapentin would solve these shortcomings of conventional dosage forms. Gabapentin in such a form can be designed to give in one or two daily doses, thus requiring less frequent dosing and improving patient compliance. Effective plasma levels can be maintained within the therapeutic range with minimum of fluctuations in blood levels of gabapentin in comparison to conventional dosage forms. The steady plasma levels will reduce side effects and increase the therapeutic efficacy.
It has been found that gabapentin is typically absorbed from the upper intestine i.e. it has a narrow absorption window and is absorbed by active transport through a large neutral amino acid (LNAA) transporter. This transporter is located in upper small intestine and has limited transport capacity and becomes saturated at high drug concentrations. Consequently, the plasma levels of gabapentin are not dose proportional and therefore, higher doses do not give proportionately
higher plasma levels. Since the LNAA transporter responsible for gabapentin absorption is
present specifically in the upper region of the intestine, the dosage form should be designed to release gabapentin in the stomach at a rate such that maximum drag is available in the intestinal segment. Conventional dosage forms release most of gabapentin in the stomach within a short time and consequently there are chances of drag being incompletely absorbed from the upper region of the intestine.
The sustained release dosage forms are designed to release drags over an extended period of time and usually throughout the GI tract. Under these circumstances, drags having a narrow absorption window tend to show poor absorption since a sustained release dosage form comprising such a drag is most likely to pass beyond the specific absorption site containing a substantial portion of the drag. This may lead to sub-therapeutic blood levels of the drag and quick termination of drag action and hence ineffective treatment.
US Patent No. 5,955,103 discloses an osmotic dosage form for sustained release of antiepileptic drags. The dosage form comprises an outer wall and an inner membrane in contact with the outer wall. Inside the dosage form, there are two layers, the drag layer in contact with an expandable polymeric layer. There is an exit orifice in the wall and membrane from which the drag release takes place. The outer wall maintains the integrity of the dosage form and protects the inner membrane and the enclosed layers from the variable pH environment of the gastrointestinal tract (GI). Once inside the stomach, water penetrates the dosage form and the expandable polymeric layer absorbs water and swells thereby pushing the drag out through the orifice to the outside of the dosage form.
The process to formulate such osmotic dosage forms requires many steps of manufacturing and is expensive. There exists a lag time before drag release takes place from these dosage forms. Also, there are chances of dose dumping in case the dosage form raptures in contact with food in the gastro-intestinal tract. Sustained release dosage form of gabapentin, which is simple to prepare and is able to maintain effective plasma concentration over an extended period of time would be desirable.
Considering the fact that gabapentin has narrow absorption window, a sustained release dosage form is desirable which can give increased exposure of gabapentin to LNAA transporter over an extended time period for efficient absorption. In order to achieve such an objective, the dosage
form with a sustained release mode can be designed to have relatively extended gastric residence
time in the stomach where the slow release of gabapentin can take place. The controlled amount of gabapentin will pass from the stomach to the upper intestine and become available for absorption. This will ensure that LNAA transporter does not become saturated thereby achieving maximal absorption of the drug.
We have now discovered that sustained release tablets of the invention could provide therapeutic levels of gabapentin with reduced number of administered doses. The rate and extent of absorption form sustained release tablets according to the invention given twice a day is same in comparison to a conventional tablet given three times a day for similar cumulative daily dose. These sustained release tablets maintain gabapentin plasma levels in a therapeutic range over an extended time period. A process for preparing the same is also provided which is less time-consuming, can be easily carried out and is economical.
Therefore, in one general aspect it relates to a sustained release tablet comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate-controlling polymer wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a sustained release tablet comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one water-swellable cellulosic polymer wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a sustained release tablet comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and hydroxypropyl methylcellulose wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a sustained release tablet comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and hydroxypropylcellulose wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a sustained release tablet comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof, hydroxypropyl methylcellulose and hydroxypropylcellulose wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a sustained release tablet comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate-controlling polymer; so that said tablet exhibits the following in-vitro dissolution profile, when measured in a USP type II dissolution apparatus, at 50 rpm, at a temperature of 37±0.5°C in 900ml of 0.06N hydrochloric acid;
at most about 50% of the drug is released in 1 hour;
at most about 65% of the drug is released in 2 hours and
at most about 85% of the drug is released in 4 hours.
In another general aspect it relates to a sustained release tablet comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate-controlling polymer wherein the tablet given twice a day is comparable in bioavailability to the conventional Neurontin® commercially available gabapentin tablet/capsule of Pfizer given thrice-a-day under fasting conditions for same cumulative daily dose.
In one general aspect it relates to a sustained release tablet comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate-controlling polymer wherein the tablet has relatively extended gastric residence time and the tablet provides for the sustained release of gabapentin in the stomach environment over a prolonged period of time.
In another general aspect it relates to a process for the preparation of a sustained release tablet comprising granulating a mixture comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate-controlling polymer and optionally other excipients; compressing the granules into a tablet wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a process for the preparation of a sustained release tablet comprising granulating a mixture comprising gabapentin or a pharmaceutically acceptable salt or
hydrates thereof and at least one water-swellable cellulosic polymer; compressing the granules into a tablet wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a process for the preparation of a sustained release tablet comprising granulating a mixture comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and hydroxypropyl methylcellulose; compressing the granules into a tablet wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a process for the preparation of a sustained release tablet comprising granulating a mixture comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and hydroxypropylcellulose; compressing the granules into a tablet wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a process for the preparation of a sustained release tablet comprising granulating a mixture comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof, hydroxypropyl methylcellulose and hydroxypropylcellulose; compressing the granules into a tablet wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours.
In another general aspect it relates to a process for the preparation of a sustained release tablet comprising granulating a mixture comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate-controlling polymer; compressing the granules into a tablet so that said tablet exhibits the following in-vitro dissolution profile, when measured in a USP type II dissolution apparatus, at 50 rpm, at a temperature of 37±0.5°C in 900ml of 0.06N hydrochloric acid;
- at most about 50% of the drug is released in 1 hour;
at most about 65% of the drug is released in 2 hours and
at most about 85%) of the drug is released in 4 hours.
In another general aspect it relates to a process for the preparation of a sustained release tablet
comprising granulating a mixture comprising gabapentin or a pharmaceutically acceptable salt or

hydrates thereof and at least one rate-controlling polymer wherein the tablet given twice a day is comparable in bioavailability to a conventional Neurontin® commercially available gabapentin tablet/capsule of Pfizer given thrice-a-day under fasting conditions for similar cumulative daily dose.
In another general aspect it relates to a process for the preparation of a sustained release tablet comprising granulating a mixture comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate-controlling polymer; compressing the granules into a tablet wherein the tablet has relatively extended gastric residence time and the tablet provides for the sustained release of gabapentin in the stomach environment over a prolonged period of time.
Gabapentin is a highly water-soluble drug having a solubility of about 1 part in 20 parts of water. The sustained release of gabapentin, which has such a high solubility, is provided by formulating a tablet comprising dispersing gabapentin in a swellable polymeric matrix. In the presence of gastric fluids, the matrix swells by imbibing water and slowly releases the incorporated gabapentin by a combination of both diffusion and erosion. There is diffusion of the drug from the swollen matrix to the surrounding fluids owing to a concentration gradient of the drug between the swollen matrix and gastric fluid. Also, in the swollen state, the polymeric matrix slowly dissolves from the surface and releases the drug. The tablet in swollen state may retain its shape for sufficiently long time.
The sustained release dosage form described herein may be prepared by blending gabapentin with at least one rate-controlling polymer and other excipients; wet granulating the blend with water or a binder solution; drying and sizing the wet granules; and compressing the granules into tablets.
Gabapentin may be present as a free base, hydrated form such as monohydrate or any other pharmaceutically acceptable salt thereof with the anion of the mineral acid (calculated as chloride content) being less than 100 ppm and lactam content being less than 0.05% weight by weight of gabapentin. Gabapentin may comprise from about l00mg to about 1200 mg by weight of the tablet.
The rate-controlling polymer may be a either hydrophilic or hydrophobic polymer; particularly suitable are polymers that swell in aqueous media. The amount of polymer in the tablet relative to
gabapentin depends upon the rate of drug release required and also upon the type and molecular
weight of the polymer and other excipients present in the formulation. Examples of suitable rate-controlling polymers include polyvinylpyrrolidone; cellulosic polymers such as hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, methylcellulose; vinyl acetate copolymers; polysaccharides (such as alginate, xanthan gum, guar gum etc.), starch and starch based polymers, polyethylene oxide, methacrylic acid copolymers, maleic anhydride/methyl vinyl ether copolymers and derivatives and mixtures thereof Particularly suitable are hydroxypropyl methylcellulose and hydroxypropylcellulose. Hydroxypropyl methylcellulose can be of different viscosity grades having viscosity from about 100 cps to about 100,000 cps. Suitable types are sold under the trade name Methocel by Dow Chemical Co. such as Methocel K4MCR, Methocel K15MCR and Methocel KIOOMCR. Hydroxypropylcellulose can also be of different viscosity grades such as sold by Aqualon under the brand name of Klucel and also by Nippon Soda Co. Ltd, Japan. Suitable grades are those having viscosity of from about 7 to about 30,000 cps. Especially suitable among these hydroxypropylcelluloses are those having viscosity of 4000 to about 30,000 cps. Besides the above, cellulose derivatives such as ethyl cellulose or cellulose acetate, methacrylates, acrylic acid polymers and copolymers, high molecular weight polyvinyl alcohols and waxes such as fatty acids and glycerides are also included. The amount of the polymer in the dosage form may vary from about 5% to about 80% by weight of the composition, in particular from about 5 to about 70%, more particularly from about 5 to 60% by weight of the composition.
The sustained release gabapentin tablets as described herein may further comprise other additives or excipients such as diluents, lubricants, binders, stabilizers etc. Suitable diluents include powdered sugar, calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, mannitol, kaolin, dry starch, sorbitol, etc. Lubricants can be talc, stearic acid, vegetable oil, calcium stearate, zinc stearate and magnesium stearate and glidants include talc, silicon dioxide and cornstarch. The binders include polyvinylpyrrolidone, polyvinylpyrrolidone/vinyl acetate copolymer; xanthan gum, guar gum; cellulose ethers such as carboxymethylcellulose, methylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose; gelatin, starch and its derivatives. The stabilizer may be poloxamer.
Gabapentin sustained release tablets may be prepared using the following steps:
1. Gabapentin is blended with rate-controlling polymer(s) and optionally with other excipients in a suitable mixer.
2. The blend of step 1 is granulated with water or a binder solution.
3. Granules are dried and sized.
4. Sized granules are mixed with other excipients such as stabilizer, lubricant, glidant and compressed into a tablet.
Alternatively, non-aqueous granulation, direct compression or dry granulation techniques may also be used to prepare tablets. In direct compression the blend of gabapentin, rate-controlling polymer(s), diluent, binder, stabilizer, lubricant is prepared and compressed into a tablet. The dry granulation process can be carried out by compaction or by preparing slugs of a mixture of gabapentin, rate-controlling polymer(s) and optionally other excipients; sizing of the material/slugs so obtained and mixing with a lubricant and compressing into a tablet.
Tablets can additionally be coated with non-rate-controlling polymer(s) compositions like Opadry® sold by Colorcon to impart aesthetic appeal. Such a coating may comprise about 2% by weight of the tablet.
Gabapentin sustained release tablet and process for the preparation thereof described herein is further illustrated by the following examples but these should not be construed as limiting the scope of the invention.

(TABLE REMOVED)

Method:
Example 1
Gabapentin was mixed with a portion of hydroxypropyl methylcellulose, microcrystalline cellulose in a rapid mixer granulator and granulated with the aqueous solution of the remaining portion of hydroxypropyl methylcellulose. The wet mass was dried and suitably sized, lubricated with magnesium stearate, colloidal silicon dioxide and compressed with appropriate tooling. The tablets were subsequently coated with OPADRY to a weight build up of about 2% w/w.
Examples 2 and 3
Gabapentin was mixed with mannitol and a portion of hydroxypropyl methylcellulose in a rapid mixer granulator and granulated with an aqueous solution/dispersion of polyvinylpyrrolidone/vinyl acetate copolymer and remaining portion of hydroxypropyl methylcellulose. The wet mass was dried and suitably sized, mixed with poloxamer, magnesium stearate, and talc and compressed with appropriate tooling. The tablets were subsequently coated with OPADRY to a weight build up of about 2% w/w.
Examples 4 and 5
Gabapentin was mixed with a portion of hydroxypropylcellulose and mannitol in a rapid mixer granulator, and granulated with an aqueous solution/dispersion of a portion of hydroxypropylcellulose. The wet mass was dried and suitably sized, mixed with remaining excipients and compressed with appropriate tooling. The tablets were subsequently coated with OPADRY to a weight buildup of about 2% w/w.
Examples 6 and 7
Gabapentin was mixed with a portion of hydroxypropyl methylcellulose and mannitol in a rapid mixer granulator and granulated with the aqueous solution/dispersion of a portion of hydroxypropyl methylcellulose. The wet mass was dried, suitably sized, blended with remaining excipients and compressed with appropriate tooling. The tablets were subsequently coated with OPADRY to a weight build up of about 2% w/w.
Tablets of Examples 1-7 were subjected to dissolution studies in a USP II apparatus in 0.06N HCl (900ml). The temperature and agitation were set at 37 °C ± 0.5 °C and 50rpm, respectively. Aliquot of sample was withdrawn at predetermined time intervals and replaced with an equal amount of fresh media. Samples were processed and analyzed suitably. Dissolution profiles of these tablets are given in Table 1.

Dissolution proflle of tablets prepared as per the compositions of examples 1-
(TABLE REMOVED)

The tablets of examples 1, 3, 4, 6 and 7 released almost the entire drug within 8 hours, while tablets of examples 2 and 5 released about 90% of drug in 12 hours.
Bioavailability study:
The sustained release tablets of Example l(test) were subjected to a bioavailability study in comparison with an immediate release formulation (NEURONTIN® 600mg as reference) in an open label, randomized, 2-way cross over study in 12 healthy male volunteers under fasting conditions. NEURONTIN® 600mg was given thrice a day every 8 hours and tablets prepared as per example 1 were given twice a day at 12 hours interval. Plasma C^ax of Reference and Test products in individual human subjects are given in Table 2. The mean Cmax and mean AUCo-24 of test and reference in the 12 human subjects is given in Table 3. The mean AUCo-24 and Cmax of test was comparable to that of reference at the end of 24 hours.
Table 2: Plasma Cmax of Reference product given thrice a day and Test product given
twice a day in human subjects.

(TABLE REMOVED)

Table 3:

Mean Cmax and AUCo-24 of Test and Reference products in human subjects

(TABLE REMOVED)

WE CLAIM:
1. A sustained release tablet comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof and at least one rate- controlling polymer and optionally other excipients; wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of unto about 12 hours.
2. The sustained release tablet according to claim 1 wherein the tablet exhibits the following in-vitro dissolution profile, when measured in a USP type II dissolution apparatus, at 50 rpm, at a temperature of 37±0.5°C in 900ml of 0.06N hydrochloric acid;
at most about 50% of the drug is released in 1 hour; at most about 65% of the drug is released in 2 hours and at most about 85%) of the drug is released in 4 hours.
3. The sustained release tablet according to claim 1 wherein the tablet given twice a day is comparable in bioavailability to conventional Neurontin® tablet/capsule given thrice a day under fasting conditions for similar cumulative daily dose.
4. The sustained release tablet according to claim 1 wherein gabapentin comprises from about l00mg to about 1200mg by weight of the tablet.
5. The sustained release tablet according to claim 1 wherein the rate-controlling polymer is from about 5% to about 80% by weight of the tablet.
6. The sustained release tablet according to claim 5 wherein the rate-controlling polymer comprises from about 5% to about 70% by weight of the tablet.
7. The sustained release tablet according to claim 6 wherein the rate-controlling polymer comprises from about 5% to about 60% by weight of the tablet.
8. The sustained release tablet according to claim 1 wherein the rate-controlling polymer comprises polyvinylpyrrolidone; cellulosic polymer; vinyl acetate copolymers; alginate, xanthan gum, guar gum; starch and starch based polymers, polyethylene oxide,
methacrylic acid copolymers, maleic anhydride/methyl vinyl ether copolymers and derivatives, ethyl cellulose, cellulose acetate, methacrylates, acrylic acid polymers and copolymers, high molecular weight polyvinyl alcohols, waxes and combinations thereof.
9. The sustained release tablet according to claim 8 wherein the rate-controlling polymer is a cellulosic polymer.
10. The sustained release tablet according to claim 9 wherein the cellulosic polymer is selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, methylcellulose and combination thereof
11. The sustained release tablet according to claim 10 wherein the cellulosic polymer is hydroxypropyl methylcellulose.
12. The sustained release tablet according to claim 11 wherein hydroxypropyl methylcellulose has viscosity of about 100 cps to about 100,000 cps.
13. The sustained release tablet according to claim 12 wherein hydroxypropyl methylcellulose has viscosity of about 15,000 cps.
14. The sustained release tablet according to claim 12 wherein hydroxypropyl methylcellulose has viscosity of about 4000 cps.
15. The sustained release tablet according to claim 10 wherein the cellulosic polymer is hydroxypropylcellulose.
16. The sustained release tablet according to claim 15 wherein the hydroxypropylcellulose has viscosity of about 7 cps to about 30,000 cps.
17. The sustained release tablet according to claim 16 wherein the hydroxypropylcellulose has viscosity of about 4000 cps.
18. The sustained release tablet according to claim 16 wherein the hydroxypropylcellulose has viscosity of about 15000 cps.
19. The sustained release tablet according to claim 10 wherein the cellulosic polymer is hydroxyethylcellulose.
20. The sustained release tablet according to claim 1 wherein the other excipients are selected from diluents, lubricants, glidants, binders, stabilizers and like.
21. The sustained release tablet according to claim 20 wherein diluent is selected from powdered sugar, calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, mannitol, kaolin, dry starch, sorbitol, and combinations thereof.
22. The sustained release tablet according to claim 20 wherein lubricant is selected from talc, stearic acid, vegetable oil, calcium stearate, zinc stearate, magnesium stearate, and combinations thereof
23. The sustained release tablet according to claim 20 wherein the glidant is selected from talc, silicon dioxide, cornstarch and combinations thereof
24. The sustained release tablet according to claim 20 wherein the binder is selected from polyvinylpyrrolidone, polyvinylpyrrolidone/vinyl acetate copolymer, xanthan gum, guar gum, cellulose gums such as carboxymethylcellulose, methylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, gelatin, starch, pregelatinized starch and combinations thereof
25. The sustained release tablet according to claim 20 wherein the stabilizer is poloxamer.
26. A process for the preparation of a sustained release tablet comprising granulating a mixture comprising gabapentin or a pharmaceutically acceptable salt or hydrates thereof; at least one rate-controlling polymer and optionally other excipients with water or binder solution; compressing the granules into a tablet wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of unto about 12 hours.
27. The process according to claim 26 wherein the tablet exhibits the following in-vitro
dissolution profile, when measured in a USP type II dissolution apparatus, at 50 rpm, at a
temperature of 37±0.5°C in 900ml of 0.06N hydrochloric acid;
at most about 50% of the drug is released in 1 hour;
- at most about 65% of the drug is released in 2 hours and
- at most about 85% of the drug is released in 4 hours.

28. The process according to claim 26 wherein the tablet given twice a day is comparable in bioavailability to conventional Neurontin® tablet/capsule given thrice a day under fasting conditions for similar cumulative daily dose.
29. The process according to claim 26 wherein the rate-controlling polymer comprises from about 5% to about 80% by weight of the tablet.
30. The process according to claim 29 wherein the rate-controlling polymer comprises from about 5% to about 70% by weight of the tablet.
31. The process according to claim 30 wherein the rate-controlling polymer comprises from about 5% to about 60% by weight of the tablet.
32. The process according to claim 26 wherein the rate-controlling polymer comprises polyvinylpyrrolidone; cellulosic polymer; vinyl acetate copolymers; alginate, xanthan gum, guar gum; starch and starch based polymers, polyethylene oxide, methacrylic acid copolymers, maleic anhydride/methyl vinyl ether copolymers and derivatives, ethyl cellulose, cellulose acetate, methacrylates, acrylic acid polymers and copolymers, high molecular weight polyvinyl alcohols, waxes and combinations thereof
33. The process according to claim 32 wherein the rate-controlling polymer is a cellulosic polymer.
34. The process according to claim 33 wherein the cellulosic polymer is selected from hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, methylcellulose and combination thereof
35. The process according to claim 34 wherein the cellulosic polymer is hydroxypropyl methylcellulose.
36. The process according to claim 35 wherein hydroxypropyl methylcellulose has viscosity of about 100 cps to about 100,000 cps.
37. The process according to claim 36 wherein hydroxypropyl methylcellulose has viscosity of about 15,000 cps.
38. The process according to claim 36 wherein hydroxypropyl methylcellulose has viscosity ofabout 4000 cps.
39. The process according to claim 34 wherein the cellulosic polymer is hydroxypropylcellulose.
40. The process according to claim 39 wherein the hydroxypropylcellulose has viscosity of about 7 cps to about 30,000 cps.
41. The process according to claim 40 wherein the hydroxypropylcellulose has viscosity of about 4000 cps.
42. The process according to claim 40 wherein the hydroxypropylcellulose has viscosity of about 15000 cps.
43. The process according to claim 34 wherein the cellulosic polymer is hydroxyethylcellulo se.
44. The process according to claim 26 wherein the other excipients comprise diluents, lubricants, glidant, binders, stabilizers and like.
45. The process according to claim 44 wherein diluent is selected from powdered sugar, calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, mannitol, kaolin, dry starch, sorbitol, and combinations thereof
46. The process according to claim 44 wherein lubricant is selected from talc, stearic acid, vegetable oil, calcium stearate, zinc stearate, magnesium stearate, and combinations thereof
47. The process according to claim 44 wherein the glidant is selected from talc, silicon dioxide, cornstarch and combinations thereof
48. The process according to claim 44 wherein the binder is selected from polyvinylpyrrolidone, polyvinylpyrrolidone/vinyl acetate copolymer, xanthan gum, guar gum, cellulose gums such as carboxymethylcellulose, methylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, gelatin, starch, pregelatinized starch and combinations thereof
49. The process according to claim 44 wlierein the stabilizer is poloxamer.
50. A process for the preparation of sustained release tablet of gabapentin comprising granulating a mixture of a therapeutically effective amount of gabapentin or a pharmaceutically acceptable salt or hydrate thereof; about 5%) to about 80% of hydroxypropyl methylcellulose having viscosity of from about 100 to about 100,000 cps and other pharmaceutical excipients; compressing the granules into a tablet; wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of unto about 12 hours.
51. A process for the preparation of sustained release tablet of gabapentin comprising granulating a mixture of a therapeutically effective amount of gabapentin or a pharmaceutically acceptable salt or hydrate thereof; about SVo to about 80%) of hydroxypropylcellulose having viscosity of from about 7 to about 30,000 cps and other
excipients with water or a binder solution; compressing the granules into a tablet; wherein the tablet provides therapeutically effective plasma levels of gabapentin for a period of up to about 12 hours. 52. A sustained release dosage form of gabapentin and process for the preparation thereof substantially as described and illustrated by the examples herein.