WO2005020978A1

WO2005020978A1 - Sustained release oral tablets of gabapentin and process for their preparation

Info

Publication number: WO2005020978A1
Application number: PCT/IB2004/002872
Authority: WO
Inventors: Manish Chawla; Rajeev Singh Raghuvanshi; Ashok Rampal
Original assignee: Ranbaxy Laboratories Limited
Priority date: 2003-09-03
Filing date: 2004-09-03
Publication date: 2005-03-10
Also published as: CN1867326A

Abstract

The present invention relates to stable sustained release oral dosage forms of gabapentin and processes for their preparation. The sustained release tablet includes an intragranular portion and an extragranular portion. The intragranular portion includes gabapentin and the extragranular portion includes one or more rate-controlling polymers.

Description

SUSTAINED RELEASE ORAL TABLETS OF GABAPENTIN AND PROCESSES FOR THEIR PREPARATION

Technical Field of the Invention The present invention relates to stable sustained release oral dosage forms of 5 gabapentin and processes for their preparation. Background of the Invention When a drug dosage form is designed for human consumption, one objective is that the drug show its maximum therapeutic efficacy with minimum side effects. Some of the side effects are inherent in the drug and can only be minimized, if not eliminated, by 10 adjusting the dosing regimen or modifying the bioavailability parameters through designing of dosage forms with sustained release of the drug. However, if the drug is susceptible to degradation and forms toxic byproducts over time as such, or due to incompatibility with the excipients present in the dosage form, its consumption can be detrimental to the health of the patient. Various pharmacopeias require that dosage forms 15 be free of these toxic degradation products or, if they are present, they should be within safe permissible limits. Gabapentin (l-(aminomethyl)cyclohexaneacetic acid) is a γ-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 20 epilepsy. Gabapentin has also been approved for neuropathic pain in some countries. Gabapentin has been reported to convert to a lactam compound (Impurity A) during preparation and storage. This lactam formation is also seen in formulations containing gabapentin. The cause of lactam formation in gabapentin formulations during storage also may be the result of catalytic effects of the excipients used in the formulation. 25 The lactam has a toxicity that exceeds that of gabapentin itself. The lethal dose (LD₅₀) of gabapentin in mice has been reported to be 8000 mg/kg while that of the corresponding lactam is 300 mg/kg. Consequently, these impurities and the potential formation of such decomposition products during storage of pharmaceutical compositions must be reduced to a minimum for reasons of safety.

30 Considering the instability of gabapentin in the dosage form and its short half life, it would be advantageous to design a sustained release dosage form of gabapentin which is stable on storage, has low lactam content and provides therapeutically effective plasma levels of gabapentin over prolonged period. Such a stable sustained release dosage form of gabapentin would not only provide a safe mode of gabapentin therapy but also other benefits, such as maintaining steady plasma levels of gabapentin and the possibility of reducing the total daily dose and frequency of dosing to once or twice a day. U.S. Patent No. 6,054,482 lists pharmaceutical excipients which are incompatible with gabapentin and also the excipients which do not have any noticeable influence on the stability of gabapentin. The list of compatible excipients includes, among others, hydroxypropyl methylcellulose. Summary of the Invention In one general aspect there is provided a process for the preparation of a sustained release tablet. The process includes forming granules that include gabapentin and one or more pharmaceutical excipients; mixing the granules with one or more rate controlling polymers; and compressing the mixture to form tablets. Embodiments of the process may include one or more of the following features.

For example, the lactam content may not exceed 0.5% by weight of gabapentin when the tablet is stored for 14 days at 60°C and 75% relative humidity. A first portion of the rate-controlling polymer may be present intragranularly and a second portion of the rate-controlling polymer may be present extragranularly. The intragranular portion may be free of any rate controlling polymer. The granules may be prepared by wet granulation or dry granulation. The rate- controlling polymer may be from about 5% to about 80% by weight of the tablet, h particular, the rate-controlling polymer may be from about 5% to about 60% by weight of the tablet. The intragranular rate-controlling polymer may be from about 0% to about 50% by weight of the granules. The rate controlling polymer may be one or more of polyvinylpyrrolidone and its derivatives; 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. In particular, the rate-controlling polymer may be one or more cellulosic polymers. The cellulosic polymer may be one or more of hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, methylcellulose and combinations thereof. For example, the cellulosic polymer may be hydroxypropyl methylcellulose and have a viscosity of about 100 cps to about 100,000 cps. The cellulosic polymer may be hydroxypropylcellulose and have a viscosity of about 7 cps to about 30,000 cps. The tablet may further include one or more additional pharmaceutical excipients. The pharmaceutical excipients may be one or more of diluents, lubricants, glidants, and binders. In another general aspect there is provided a sustained release tablet that includes an intragranular portion and an extragranular portion. The intragranular portion includes gabapentin and the extragranular portion includes one or more rate-controlling polymers. Embodiments of the tablet may include one or more of the following features. For example, the lactam content may not exceed 0.5% by weight of the gabapentin tablet when stored for 14 days at 60°C and 75% relative humidity. A first portion of the rate controlling polymer may be present intragranularly and a second portion of the rate-controlling polymer may be present extragranularly. The intragranular portion may be free of any rate-controlling polymer. The rate-controlling polymer may make up from about 5% to about 80% by weight of the tablet and, in particular, from about 5% to about 60% by weight of the tablet. The intragranular rate- controlling polymer may make up from about 0% to about 50% by weight of the granules. The rate controlling polymer may be one or more of polyvinylpyrrolidone and its derivatives; 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. hi particular, the rate-controlling polymer may be a cellulosic polymer and the cellulosic polymer may be one or more of hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, methylcellulose and combinations thereof. The tablet may further include one or more pharmaceutical excipients. The pharmaceutical excipients may be one or more of diluents, lubricants, glidants, and binders. In another general aspect there is provided a method of treating a medical condition responsive to gabapentin therapy. The method includes administering to a patient a sustained release tablet that includes an intragranular portion and an extragranular portion. The intragranular portion includes gabapentin and the extragranular portion includes one or more rate-controlling polymers. Embodiments of the method may include one or more of the following features or those described above. For example, the medical condition may be either or both of epilepsy and neuropathic pain. The details of one or more embodiments of the inventions are set forth in the description below. Other features, objects and advantages of the inventions will be apparent from the description and claims. Detailed Description of the Invention The incompatibility of gabapentin with some of the commonly used and easily available pharmaceutical excipients, in particular the rate-controlling polymers, restricts the choice to only few excipients. This limited range of acceptable excipients makes difficult the task of developing a stable sustained release dosage form with desired release characteristics of gabapentin. A process which can widen the scope of available excipients for use in the preparation of stable sustained release dosage forms of gabapentin is needed. In the present invention we have discovered that the excipients, in particular the rate-controlling polymers that are incompatible with gabapentin, can be used in gabapentin compositions without compromising the stability of gabapentin. This result can be achieved by a) extragranular addition of the rate controlling polymers, or b) intragranular addition of a part of the rate controlling polymer and extragranular addition of the remaining part of the rate controlling polymer. This process results in an improved stability of the gabapentin compositions as compared to the formulations prepared with the whole of the rate controlling polymer added intragranularly. The present process resulted in gabapentin compositions with further reduced lactam content. To determine the stability of the gabapentin formulations described herein, the inventors have performed experiments to evaluate the use of accelerated aging studies on lactam formation and stability. These studies and their results are described below followed by a description of the formulations and process used to make the formulations. The fundamental aims of accelerated stability testing are to ensure that the product will be safe and efficacious when administered to the patient after being subjected to the anticipated stresses of storage, transport and administration. The product should remain free from toxic substances and the content of active ingredients should comply with the label claim at least until the expiry date. The real time stability testing of a dosage form under normal conditions of storage may stretch for years. The storage of a dosage form under accelerated conditions of temperature and relative humidity provide an approximate idea about the stability of the dosage form in the actual usage. For evaluating the stability of a formulation in a short period of time, we have developed a correlation between the lactam produced in a formulation when stored for 14 days at 60°C and 75% relative humidity (RH) and the same produced at 40°C and 75% RH when stored for 3 months in sealed HDPE bottles. The compositions of various formulations that have been tested under these conditions of storage are listed in Table 1. The lactam content of these formulations under these two conditions of storage is listed in Table 2, and Figure 1 depicts graphically the given correlation. This correlation is described by the equation of a straight line (R² = 0.9706): y = 0.6797x + 0.0515 Where, y = Lactam content produced at 40°C/75 % RH at 3 month, and x = Lactam content produced at 60°C/75 % RH at 14 days. By the above-mentioned correlation, it is implied that a 0.5% w/w of lactam in a formulation stored for 14 days at 60°C and 75% RH corresponds to 0.4%w/w of lactam in that formulation stored for 3 months at 40°C and 75% RH. Table 1 Compositions of formulations stored for 14 days at 60°C/75% RH and for three months at 40°C/75%RH

Table 2 Stability data of formulations stored for 14 days at 60°C/75% RH and for three months at 40°C/75%RH

Figure 1 Correlation between Lactam content at 60°C/75% RH for 14 days and 40°C/75% RH for three months

0 0.₅ 1 1.5 2 Lactam content (w/w%) at 60C 7S% RH

Accelerated stability studies performed at higher temperatures such as 50°C or greater may result in reactions which usually do not occur at room temperature. Therefore, a possibility exist that a formulation which shows more than 0.5% w/w of lactam when stored for 14 days at 60°C/75% RH may show lactam content of 0.4% w/w or less when stored for three months at 40°C/75% RH. With this understanding of accelerated aging and stability, the inventors have developed processes for making the stable sustained release tablets containing gabapentin. Thus, in one general aspect, a process for the preparation of a stable sustained release tablet of gabapentin has the rate-controlling polymer present extragranularly. When the tablet is kept for 14 days at 60°C and 75% relative humidity, the lactam content does not exceed 0.5% by weight of gabapentin. In another general aspect, a process for the preparation of a stable sustained release tablet of gabapentin has a part of the rate-controlling polymer present intragranularly and the remaining part present extragranularly. Again, when the tablet is kept for 14 days at 60°C and 75% relative humidity, the lactam content does not exceed 0.5% by weight of gabapentin. In another general aspect, a wet granulation process for the preparation of a stable sustained release tablet of gabapentin includes the following steps: 1. granulating a mixture that includes gabapentin, pharmaceutical excipients and, optionally, rate-controlling polymer with a granulating liquid; and 2. drying and mixing the granules with rate controlling polymer and compressing the blend into a tablet; and In this process, when the tablet is kept for 14 days at 60°C and 75% relative humidity, the lactam content does not exceed 0.5%) by weight of gabapentin. In another general aspect, a dry granulation process for the preparation of a stable sustained release tablet of gabapentin includes the following steps: 1. blending gabapentin, pharmaceutical excipients and, optionally, rate- controlling polymer; 2. compacting or slugging the blend of step (1 ); 3. sizing the compacts or slugs into granules; and 4. mixing the granules with rate controlling polymer and compressing the blend into a tablet; and In this process, when the tablet is kept for 14 days at 60°C and 75% relative humidity, the lactam content does not exceed 0.5% by weight of gabapentin. Thus, the stable sustained release tablets of gabapentin can include: (1) gabapentin mtragranularly and rate-controlling polymer extragranularly; and (2) gabapentin and a part of rate controlling polymer mtragranularly and the remaining part of the rate-controlling polymer extragranularly. These tablets may be used, for example, to treat a medical condition responsive to gabapentin therapy. The method of treating includes administering a stable sustained release tablet of gabapentin, the tablet including rate controlling polymer present extragranularly and the tablet, when kept for 14 days at 60 °C ^• and 15% relative humidity, has a lactam content that does not exceed 0.5%) by weight of gabapentin. It has been observed that for a given rate-controlling polymer, the stability of gabapentin tablet is influenced by the amount of the polymer that is present mtragranularly or extragranularly. The stability is improved when the amount of rate-controlling polymer is decreased in the intragranular phase. With this consideration, the processes described herein provide flexibility and broaden the range of pharmaceutical excipients, particularly rate-controlling polymers, that can be used for preparing stable sustained release dosage forms of gabapentin. The rate controlling polymers which show incompatibility with gabapentin can still be used to prepare stable compositions when largely used as extragranular polymers. The process is economical and can be easily carried out to prepare stable sustained release tablets of gabapentin. The process provides stable gabapentin sustained release tablets which provide therapeutically effective plasma levels of gabapentin for a period of up to about 24 hours. As indicated above, the process involves granulation and the granules can be prepared by a wet granulation or a dry granulation process. Therefore in one embodiment, granules can be prepared by blending gabapentin, other pharmaceutical excipients and, optionally, apart of the rate-controlling polymer; granulating with a granulating liquid; drying; sizing; mixing with rate-controlling polymer and other extragranular excipients; and compressing to make tablets. In another embodiment, granules can be prepared by blending gabapentin, other pharmaceutical excipients and, optionally, a part of rate controlling polymer; compacting or slugging the above blend; sizing; mixing with rate-controlling polymer and other extragranular excipients; and compressing to make tablets. The stability conditions as defined herein include tolerance of ± 2°C in temperature and a tolerance of ± 5% in relative humidity. Gabapentin may be present as a free base, hydrated form such as monohydrate or any other pharmaceutically acceptable salt thereof. Gabapentin may make up from about 100 mg to about 1200 mg by weight of the tablet. The rate-controlling polymer may be either a hydrophilic or a 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. The rate-controlling polymer may be present as a combination of intragranular polymer and extragranular polymer or may be present completely as an extragranular polymer. The intragranular or extragranular rate-controlling polymers may be same or different. The amount of intragranular rate-controlling polymer may depend on the type being used and also on the extent of incompatibility with gabapentin. hi general, the amount of the rate-controlling polymer in the dosage form may vary from about 5% to about 80%) by weight of the tablet, in particular from about 5 to about 70%, more particularly from about 5 to 60% by weight of the tablet. The intragranular rate- controlling polymer may make up from about 0% to about 50% by weight of the granules while the extragranular polymer may comprise from 5% to about 80% by weight of the tablet. Examples of suitable rate-controlling polymers include polyvinylpyrrolidone (PVP) and its derivatives such as copolyvidone, mixtures of PVP and polyvinylacetates, such as Kollidon SR; 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 rate-controlling polymers are hydroxypropyl methylcellulose and hydroxypropylcellulose. The hydroxypropyl methylcellulose can be of different viscosity grades having viscosity ranging from about 100 cps to about 100,000 cps, in particular about 4000 cps to about 15,000 cps. Suitable types of hydroxypropyl methylcellulose are sold under the trade name Methocel by Dow Chemical Co. (e.g., Methocel K4MCR, Methocel K15MCR and Methocel Kl 00MCR). Hydroxypropylcellulose can also be of different viscosity grades such as those sold by Aqualon under the brand name of Klucel and by Nippon Soda Co. Ltd, Japan. Suitable grades are those having a viscosity of from about 7 cps to about 30,000 cps. Especially suitable among these hydroxypropylcelluloses are those having viscosity of 4000 cps 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 sustained release gabapentin tablets as described herein may further include additional and other additives or pharmaceutical excipients such as diluents, lubricants, binders, etc. Suitable diluents include one or more of powdered sugar, calcium phosphate, calcium sulfate, microcrystalline cellulose, lactose, mamiitol, kaolin, dry starch, sorbitol, etc. Suitable lubricants include one or more of talc, stearic acid, vegetable oil, calcium stearate, zinc stearate and magnesium stearate and glidants include talc, silicon dioxide and cornstarch. Suitable binders include one or more of 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 granulating liquid can be, but is not limited to, one or more of water, ethanol, isopropyl alcohol, acetone, dichloromethane and the like. Alternatively, the binder can be dissolved in the granulating liquid and used as a solution/dispersion. Accordingly, one process for the preparation of stable gabapentin sustained release tablets includes the following steps: 1. granulating a mixture that includes gabapentin and, optionally, a rate controlling polymer, with a solution/dispersion of a binder; 2. drying and mixing the granules of step 1 with a rate controlling polymer and other pharmaceutical excipients such as diluents, lubricants, glidants and binders and compressing the blend into a tablet using appropriate tooling. Another process for the preparation of stable gabapentin sustained release tablets includes the following steps: 1. granulating a mixture comprising gabapentin and hydroxypropylcellulose with a solution/dispersion of hydroxypropylcellulose; 2. drying and mixing the granules with hydroxypropyl methylcellulose or hydroxypropylcellulose and other pharmaceutical excipients such as diluents, lubricants, glidants and binders and compressing the blend into a tablet using appropriate tooling. The tablets made using the processes described herein can additionally be coated with one or more non-rate-controlling polymer compositions such as Opadry® sold by Colorcon to impart aesthetic appeal. Such a coating may include about 2% by weight of the tablet. The process for the preparation of stable gabapentin tablets described herein is further illustrated by the following examples but these should not be construed as limiting the scope of the invention.

Procedure:

Examples 1 and 2 Gabapentin was mixed with a portion of hydroxypropylcellulose and granulated with a second portion of hydroxypropylcellulose dissolved in purified water. The granules were dried, sized, mixed with extragranular hydroxypropyl methylcellulose, hydroxypropylcellulose (Example 2), mannitol, copolyvidone, poloxamer, magnesium stearate and talc, and compressed to form a tablet.

Examples 3 and 4 Gabapentin was mixed with a first portion of hydroxypropylcellulose and granulated with a second portion of hydroxypropylcellulose dissolved in isopropyl alcohol/dichloromethane mixture. The granules were dried, sized, mixed with the extragranular portion of hydroxypropylcellulose, mannitol, copolyvidone, poloxamer, magnesium stearate and talc, and compressed to form a tablet.

Example 5 Gabapentin was mixed with a first portion of hydroxypropylcellulose and granulated with the remaining portion of hydroxypropylcellulose dissolved in purified water. The granules were dried, sized, mixed with mannitol, copolyvidone, poloxamer, magnesium stearate and talc, and compressed to form a tablet.

Example 6 Gabapentin was mixed with a first portion of hydroxypropyl methylcellulose and granulated with the remaining portion of hydroxypropyl methylcellulose dissolved in purified water. The granules were dried, sized, mixed with mannitol, copolyvidone, poloxamer, magnesium stearate and talc, and compressed to form a tablet.

Example 7 The same procedure was followed as in Example 6 except that half the amount of hydroxypropyl methylcellulose was added extragranularly.

Example 8 Gabapentin was mixed with a first portion of hydroxypropylcellulose and granulated with the remaining portion of hydroxypropylcellulose dissolved in isopropyl alcohol. The granules were dried, mixed with hydroxypropyl methylcellulose, mannitol, copolyvidone, poloxamer, magnesium stearate and talc, and compressed to form a tablet. Tablets formed according to Examples 1-8 were kept for 14 days at 60°C and 75% relative humidity in sealed HDPE bottles and then the stability of the tablets was evaluated. The resulting stability data is provided in Table 3. The dissolution profile of the tablets of Examples 1-4 and 8 measured in a USP type II dissolution apparatus, at 50 rpm, at a temperature of 37±0.5°C in 900 ml of 0.06 N HC1 is provided in Table 4.

Table 3 Stability data of tablets of Examples 1-8 when stored for 14 days at 60°C and 75% relative humidity (RH)

The stability data provided in Table 3 clearly shows that the stability of a gabapentin formulation is substantially increased in direct proportion to the amount of extragranularly added rate controlling polymer. The tablets of Examples 1, 2 and 8 containing extragranular hydroxypropyl methylcellulose are more stable in comparison to the tablets of Examples 6 and 7 which contain intragranular hydroxypropyl methylcellulose. Further, the tablets of Examples 3 and 4 containing intragranular as well as extragranular hydroxypropylcellulose showed improved stability in comparison to the tablets of Example 5, which contained only intragranular hydroxypropylcellulose. A comparison of Examples 3 and 4 clearly indicates a further improvement in stability when the amount of the intragranular polymer is substantially reduced. A more stable formulation was obtained in the case of Example 7 when the amount of hydroxypropyl methylcellulose was increased from the intragranular phase to the extragranular phase relative to the tablets of Example 6, which contains hydroxypropyl methylcellulose in the intragranular phase only. It should be noted that U.S. Patent No. 6,054,482, described above, lists hydroxypropyl methylcellulose as a compatible excipient with gabapentin. However, an increase in the lactam content was observed when gabapentin was formulated with hydroxypropyl methylcellulose and the formulation was found to be highly unstable upon storage (see Examples 6 and 7 and Table 3 herein).

Table 4 Dissolution profiles of tablets of Examples 1- 4 and 8 as measured in a USP type II dissolution apparatus, at 50 rpm, at a temperature of 37±0.5°C in 900 ml of 0.06 N HC1

As indicated if Table 4, the tablets of these examples have a dissolution profile which results in the entirety of the gabapentin being delivered over the course of about twelve hours. 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.

Claims

WE CLAIM:

1. A process for the preparation of a sustained release tablet, the process comprising: forming granules comprising gabapentin and one or more pharmaceutical excipients; mixing the granules with one or more rate controlling polymers; and compressing the mixture to form tablets.

2. The process of claim 1, wherein the lactam content does not exceed 0.5% by weight of gabapentm when the tablet is stored for 14 days at 60°C and 75%) relative humidity.

3. The process of claim 1 , wherein a first portion of the rate-controlling polymer is present mtragranularly and a second portion of the rate-controlling polymer is present extragranularly.

4. The process according to claim 1, wherein the granules are prepared by wet granulation.

5. The process according to claim 1, wherein the granules are prepared by dry granulation.

6. The process according to claim 1, wherein the rate-controlling polymer comprises from about 5% to about 80% by weight of the tablet.

7. The process according to claim 6, wherein the rate-controlling polymer comprises from about 5% to about 60% by weight of the tablet.

8. The process according to claim 3, wherein the intragranular rate-controlling polymer comprises from about 0% to about 50% by weight of the granules.

9. The process according to claim 3, wherein the rate controlling polymer comprises one or more of polyvmylpyrrolidone and its derivatives; cellulosic polymer; vinyl acetate copolymers; alginate, xanthan gum, guar gum; starch and starch based polymers, polyethylene oxide, methacryhc 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.

10. The process according to claim 9 wherein the rate-controlling polymer comprises one or more cellulosic polymers.

11. The process according to claim 10, wherein the cellulosic polymer comprises one or more of hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, methylcellulose and combinations thereof.

12. The process according to claim 11 , wherein the cellulosic polymer comprises hydroxypropyl methylcellulose.

13. The process according to claim 12, wherein the hydroxypropyl methylcellulose has a viscosity of about 100 cps to about 100,000 cps.

14. The process according to claim 11, wherein the cellulosic polymer comprises hydroxypropylcellulose.

15. The process according to claim 14, wherein the hydroxypropylcellulose has a viscosity of about 7 cps to about 30,000 cps.

16. The process according to claim 1, wherein the tablet further comprises one or more additional pharmaceutical excipients.

17. The process according to claim 16, wherein the pharmaceutical excipients comprises one or more of diluents, lubricants, glidants, and binders.

18. The process according to claim 1, wherein the intragranular portion is free of any rate controlling polymer.

19. A sustained release tablet comprising an intragranular portion and an extragranular portion, the intragranular portion comprising gabapentin and the extragranular portion comprising one or more rate-controlling polymers.

20. The tablet according to claim 19, wherein the lactam content does not exceed 0.5% by weight of the gabapentin tablet when stored for 14 days at 60°C and 75% relative humidity.

21. The tablet according to claim 19, wherein a first portion of the rate controlling polymer is present mtragranularly and a second portion of the rate-controlling polymer is present extragranularly.

22. The tablet according to claim 19, wherein the rate-controlling polymer comprises from about 5% to about 80% by weight of the tablet.

23. The tablet according to claim 19, wherein the rate-controlling polymer comprises from about 5% to about 60% by weight of the tablet.

24. The tablet according to claim 21, wherein the intragranular rate-controlling polymer comprises from about 0% to about 50% by weight of the granules.

25. The tablet according to claim 21, wherein the rate controlling polymer comprises one or more of polyvinylpyrrolidone and its derivatives; cellulosic polymer; vinyl acetate copolymers; alginate, xanthan gum, guar gum; starch and starch based polymers, polyethylene oxide, methacryhc 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.

26. The tablet according to claim 25, wherein the rate-controlling polymer comprises a cellulosic polymer.

27. The tablet according to claim 32, wherein the cellulosic polymer comprises one or more of hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, methylcellulose and combinations thereof.

28. The tablet according to claim 19, wherein the tablet further comprises one or more pharmaceutical excipients.

29. The tablet according to claim 28, wherein the pharmaceutical excipients comprises one or more of diluents, lubricants, glidants, and binders.

30. The tablet according to claim 19, wherein the intragranular portion is free of any rate-controlling polymer.

31. A method of treating a medical condition responsive to gabapentin therapy, the method comprising administering a sustained release tablet comprising an intragranular portion and an extragranular portion, the intragranular portion comprising gabapentin and the extragranular portion comprising one or more rate-controlling polymers.

32. The method according to claim 32, wherein the medical condition comprising either or both of epilepsy and neuropathic pain.