CN1832736A - Stable sustained release oral dosage form of gabapentin - Google Patents
Stable sustained release oral dosage form of gabapentin Download PDFInfo
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- CN1832736A CN1832736A CNA2004800224971A CN200480022497A CN1832736A CN 1832736 A CN1832736 A CN 1832736A CN A2004800224971 A CNA2004800224971 A CN A2004800224971A CN 200480022497 A CN200480022497 A CN 200480022497A CN 1832736 A CN1832736 A CN 1832736A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
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Abstract
The present invention relates to stable slow released orally taken gabapentin preparations and their preparation process. The stable slow released tablet is prepared with granule. The granule contains gabapentin; one or several kinds of hydrophilic rate controlling polymer selected from hydroxypropyl cellulose, polyvinyl pyrrolidone and its derivative, and polysaccharide gum; and one or several kinds of optional excipient.
Description
Technical field
The present invention relates to the stable sustained-release oral dosage forms of gabapentin and prepare the method for these dosage forms.
Background technology
When a kind of human pharmaceutical dosage form of design, need medicine to give play to its maximum curative effect and minimum side effect.By design the dosage form adjustment dosage regimen of medicament slow release or change bioavailability parameter only can be minimized, rather than eliminate the inherent side effect of some medicines.If but medicine is easy to degraded, and is formed with toxic byproduct in time, use it just may be harmful to patient health.Various pharmacopeia require dosage forms must not contain these deleterious catabolites or if present, should be in the safety allowed band.
Gabapentin (1-(amino methyl) cyclohexane extraction acetic acid) is the a#-amino acid analogue of effectively treating epilepsy.Gabapentin be used for auxiliary treatment epilepsy adult patient with without the extensive partial seizure of Secondary cases.Gabapentin also has been approved for the treatment neuralgia in some countries.
It is reported that between preparation and storage life, gabapentin can change into deleterious lactam compound.In containing the preparation of gabapentin, also found the formation of this lactams.Between the storage life, the formation of lactams obviously is the result of the catalytic effect of used excipient in the preparation.The toxicity that lactams had surpasses gabapentin itself.It is reported that gabapentin is to the fatal dose (LD of mice
50) be 8,000 mg/kg, and the fatal dose of corresponding lactams is 300 mg/kg.As a result, for safety, must be reduced to these impurity and this catabolite that during the storage pharmaceutical compositions, may form minimum.
Consider that unstability and the half-life thereof of gabapentin in dosage form is short, should design a kind of slow release formulation of gabapentin, it between the storage life be stable, lactams content is low and the gabapentin for the treatment of effective plasma level concentration was provided in time expand.The stable slow release formulation of these of gabapentin not only provides the gabapentin treatment of safe mode, other advantage also is provided, has for example kept the stable of gabapentin blood plasma level and reduce total daily dose and administration frequency is reduced to the probability of every day 1 or 2 times.
U.S. Patent number 6,054,482 provide a series of adjuvants, it is said that their obviously do not influence the stability of gabapentin.This series comprises hydroxypropyl emthylcellulose etc.In addition, Application No. 2003/0100611 discloses the gastric retentive dosage forms of the gabapentin that contains hydrophilic polymer.Disclosed illustrative polymers is drawn together high viscosity or high-molecular weight hydroxypropyl emthylcellulose.As if equally, technology is before told us, hydroxypropyl emthylcellulose and gabapentin are compatible.
Open
Summary of the invention
One aspect of the present invention provides a kind of stable sustained-release tablet by preparation of granules.Comprise gabapentin in the granule; One or more are selected from the hydrophilic rate control polymer of hydroxypropyl cellulose, kollidon and derivant thereof and polysaccharide glue; And one or more optional drug excipients.
The embodiment of slow releasing tablet can comprise one or more of following feature.For example, when storing three months in 40 ℃ and 75% relative humidity, the lactams content of tablet can not surpass 0.6% of gabapentin weight.This tablet can reach the gabapentin that treatment effective plasma level concentration is provided in about 24 hours.Be distributed as with 50rpm, 37 ℃ ± 0.5 ℃ temperature record slow releasing tablet in 900 milliliters of 0.06N hydrochloric acid dissolution with USPII type dissolution equipment, at least 90% gabapentin discharged in 4-12 hour.Say that more specifically at least 90% gabapentin can discharge in 8-12 hour.
Gabapentin can account for about 100-1200 milligram of tablet weight.
The viscosity of hydroxypropyl cellulose can be between about 7 centipoises and about 30,000 centipoises.Specifically, the viscosity of hydroxypropyl cellulose can be between about 4,000 centipoises and about 15,000 centipoises.
The optional physical mixture of polyvinylpyrrolidone derivant from crospovidone, copolyvidone (copolyvidone) and polyvinylpyrrolidone and polyvinyl acetate.Polysaccharide glue can be selected from guar gum, arabic gum, xanthan gum, locust bean gum, karaya and gum tragacanth or its combination.
Drug excipient can be selected from diluent, binding agent, lubricant and fluidizer.Can prepare the slow releasing tablet that does not contain hydroxymethyl-propyl cellulose in the granule.Also can comprise in the slow releasing tablet and blended one or more drug excipients of granule.
In another general aspect, provide the method for preparing the stable sustained-release tablet, this method comprises:
Make the mixture granulation of gabapentin and one or more hydrophilic rate control polymers with granulation liquid or binder solution, described polymer is selected from hydroxypropyl cellulose; Polyvinylpyrrolidone and derivant thereof and polysaccharide glue or its combination.
Dry these granules;
Dried granules is mixed with one or more drug excipients, form mixture; With
With the mixture compacting in flakes.
The embodiment of this method can comprise one or more in the following feature.For example, when storing three months under 40 ℃ and 75% relative humidity, the lactams content of tablet can not surpass 0.6% of gabapentin weight.This tablet can reach the gabapentin that treatment effective plasma level level is provided in about 24 hours.Be distributed as with 50rpm, 37 ℃ ± 0.5 ℃ temperature record slow releasing tablet in 900 milliliters of 0.06N hydrochloric acid dissolution with USP II type dissolution equipment, at least 90% gabapentin discharged in 4-12 hour.Say that more specifically at least 90% gabapentin can discharge in 8-12 hour.
Contain the 100-1200 milligram gabapentin of having an appointment in the described tablet.The viscosity of hydroxypropyl cellulose can be between about 7 centipoises and about 30,000 centipoises.Specifically, the viscosity of hydroxypropyl cellulose can be between about 4,000 centipoises and about 15,000 centipoises.
The polyvinylpyrrolidone derivant is selected from the physical mixture of crospovidone, copolyvidone and polyvinylpyrrolidone and polyvinyl acetate.Polysaccharide glue is selected from guar gum, arabic gum, xanthan gum, locust bean gum, karaya and gum tragacanth or its combination.The other medicines excipient is selected from diluent, lubricant and fluidizer.
This method also can comprise one or more drug excipients of mixture granulation with gabapentin and one or more hydrophilic rate control polymers.
In another general aspect, provide a kind of method for the treatment of medical symptom.This method comprises to be provided by containing gabapentin, be selected from one or more hydrophilic rate control polymers of hydroxypropyl cellulose, polyvinylpyrrolidone and derivant thereof and polysaccharide glue, and the slow-releasing tablets of oral medicine of the preparation of granules of one or more optional drug excipients.
The embodiment of Therapeutic Method can comprise one or more of following or above-mentioned feature.From description and claims, will obviously find out other features, objects and advantages of the present invention.
Detailed Description Of The Invention
According to the knowledge of above-mentioned prior art, we prepare gabapentin tablets with high viscosity and high molecular weight hydroxypropyl methyl cellulose.Yet unlike the prior art be, these tablets lactams content in storage raise (referring to the embodiment 5 of this paper and 6 and table 4).In fact improved lactams content because find high molecular or high viscosity hydroxypropyl emthylcellulose, so it is we have to carry out arduous research, in fact compatible with gabapentin with cellulosic material or the hydrophilic polymer of determining which kind of alkyl replacement.
The result of these work is astonishing, and we find that the available hydrophilic polymer that is selected from hydroxypropyl cellulose, polyvinylpyrrolidone and derivant thereof and polysaccharide glue and one or more pharmaceutically acceptable excipient prepares stable slow release gabapentin tablets.When these slow releasing tablets were placed three months in 40 ℃ and 75% relative humidity, lactams content was no more than 0.6% of gabapentin weight.Believe that these gabapentin slow releasing tablets can maintain in the therapeutic domain in the plasma concentration that reaches in about 24 hours time expand gabapentin.This can pass through, and for example changes in the granule, also may be that the outer polymer concentration of granule is finished.
Stability condition defined herein comprises in the temperature ± 2 ℃ tolerance and relative humidity in ± 5% tolerance.
Gabapentin can free alkali, water and form such as monohydrate or its any other pharmaceutically acceptable salt exist.By the weight of tablet, gabapentin accounts for 100 milligrams to 1200 milligrams.
The viscosity grade of hydroxypropyl cellulose used herein can be different, as the hydroxypropyl cellulose that Aqualon sells with trade mark Klucel and Japanese Nippon Soda Co.Ltd sells.Suitable rank is that viscosity is about 7-30,000 centipoise.Especially suitable in these hydroxypropyl celluloses is the about 4000-30 of viscosity, the hydroxypropyl cellulose of 000 centipoise.In particle weight, the amount of hydroxypropyl cellulose can be about 3%-40% usually, specifically is about 5%-30%, more specifically is about 5%-25%.
Polyvinylpyrrolidone or PVP refer to contain the polymer of N-vinylpyrrolidone as monomeric unit, it has a lot of titles in pharmaceuticals industry, comprising polyvinyl pyrrolidone (povidone), polyvidone, polyvidonum, solubility polyvidonum and poly-(l-vinyl-2-pyrrolidone).Also comprise the Kollidon CL and the Kollidon CL-M that can buy, they are crospolyvinylpyrrolidone, are also referred to as crospovidone.The polyvinylpyrrolidone derivant comprises the copolymer of N-vinyl-2-Pyrrolidone and vinyl acetate, is called copolyvidone (copolyvidon/copolyvidone/copolyvidonum).The physical mixture that also comprises polyvinylpyrrolidone and polyvinyl acetate.For example, the ratio of these mixture can be 20: 80 (PVP: polyvinyl acetate), as Kollidon SR, but be not limited thereto.Obviously also can adopt other derivant of polyvinylpyrrolidone well known by persons skilled in the art.The molecular weight ranges of polyvinylpyrrolidone is very wide.Especially suitable is molecular weight is about 8,000-1, and the polyvinylpyrrolidone rank between 300,000 is as Plasdone K-90, Plasdone K-90D.By particle weight, the amount of polyvinylpyrrolidone and derivant thereof generally is about 3-40%, especially is about 3-30%.
Polysaccharide glue can be selected from guar gum, arabic gum, xanthan gum, locust bean gum, karaya and gum tragacanth.Especially suitable is guar gum.By particle weight, the amount of polysaccharide glue generally be about 3-80%, especially be about 3-70%, more specifically be about 3-60%.
The other medicines excipient is selected from diluent, lubricant and fluidizer.Suitable diluent comprises powdered sugar, calcium phosphate, calcium sulfate, microcrystalline Cellulose, lactose, mannitol, Kaolin, dried starch, sorbitol etc.Suitable bonding comprises polyvinylpyrrolidone and derivant thereof; Xanthan gum, guar gum; Cellulose ether such as carboxymethyl cellulose, methylcellulose, hydroxypropyl emthylcellulose (only outside the granule, non-particulate interior), hydroxypropyl cellulose, ethyl cellulose; Gelatin, starch and derivant thereof.Granulation liquid can be water, ethanol, isopropyl alcohol, acetone, dichloromethane etc., but is not limited thereto.Perhaps, binding agent can be dissolved in the granulation liquid, use with solution.Lubricant can be Pulvis Talci, stearic acid, vegetable oil, calcium stearate, zinc stearate and magnesium stearate, and fluidizer comprises Pulvis Talci, silicon dioxide and corn starch.
In one embodiment, can prepare stable gabapentin slow releasing tablet by following steps:
1. in a mixer, gabapentin and hydrophilic rate control polymer such as hydroxypropyl cellulose, polyvinylpyrrolidone and derivant thereof or polysaccharide glue and other medicines excipient (but not being HPMC) are mixed.
2. with the mixture of granulation liquid or binder solution granulation step (1).
3. dried particles also screens granule by size.
4. size is also suppressed in flakes through the granule and the other medicines mixed with excipients of screening.
In another embodiment, can prepare stable gabapentin slow releasing tablet by following steps:
1. in a mixer, gabapentin is mixed with a part of hydroxypropyl cellulose.
2. use the mixture of the granulation liquid solution granulation step (1) of residue hydroxypropyl cellulose.
3. dried particles also screens granule by size.
4. size is also suppressed in flakes through the granule and the other medicines mixed with excipients of screening.
In addition, available non-rate control polymer compositions is as the Opadry coated tablet of Colorcon sale, to play effect attractive in appearance.This coating can account for 2% of tablet weight.
Further specify stable gabapentin slow releasing tablet as herein described and preparation method thereof by following examples, but should not think that these embodiment have limited the scope of the invention.
Research before dosage form is determined
In the excipient Study on Compatibility, measured the compatibility of other medicines excipient such as gabapentin and hydroxypropyl cellulose, polyvinylpyrrolidone, copolyvidone, guar gum and hydroxypropyl emthylcellulose.With gabapentin and these polymer mixed, with these mixture of pure water granulation, dried particles, screening and its compacting is in blocks by size.Then this tablet is placed the HDPE bottle of sealing, in 40 ℃ and 75% relative humidity, placed three months.Stability data sees the following form 1.
The stability data of research before table 1 dosage form is determined
| Excipient/(particulate weight %) | Lactams content (weight %) | |
| Initial | 3 months/40 ℃/75%RH | |
| Gabapentin (100%) | 0.080 | 0.077 |
| Gabapentin+hydroxypropyl cellulose (12.4%) | 0.024 | 0.268 |
| Gabapentin+polyvinylpyrrolidone (5.2%) | 0.049 | 0.202 |
| Gabapentin+guar gum (12%) | 0.014 | 0.302 |
| Gabapentin+hydroxypropyl emthylcellulose (10.9%) | 0.083 | 0.816 |
| Gabapentin+copolyvidone (2%) | 0.034 * | 0.053 * |
*40 ℃/75%RH 2 months
Embodiment 1-4
| Composition | Weight (milligram) | |||
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | |
| Gabapentin | 900 | 900 | 900 | 900 |
| Hydroxypropyl cellulose | 120 | 100 | 100 | 265 |
| Mannitol | 60.5 | 81 | 93 | 15.5 |
| Poloxamer | 15 | 12 | 12 | 15 |
| Copolyvidone | 12 | 12 | -- | 12 |
| Magnesium stearate | 20 | 15 | 15 | 20 |
| Pulvis Talci | 22.5 | 15 | 15 | 22.5 |
| Amount to | 1150 | 1135 | 1135 | 1250 |
Conventional steps:
A part of hydroxypropyl cellulose is mixed with gabapentin, with the purification of aqueous solutions granulation of hydroxypropyl cellulose remainder.Dried particles and screening by size mix with mannitol, copolyvidone (embodiment 1,2 and 4), poloxamer, magnesium stearate and Pulvis Talci, and compacting in flakes.Then this tablet is placed the HDPE bottle of sealing, in 40 ℃ and 75% relative humidity, placed three months.Stability data sees Table 2, and this dosage form of data show is stable.
When table 2 stores three months in 40 ℃ and 75% relative humidity (RH)
The stability data of the tablet of embodiment 1-4
| Lactams content (weight %) | ||||
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | |
| Initial | 0.034 | 0.035 | 0.032 | 0.039 |
| 3 months/40 ℃/75%RH | 0.337 | 0.249 | 0.236 | 0.514 |
With USP II type dissolution equipment with 50rpm, 37 ℃ ± 0.5 ℃ temperature, the dissolution of the tablet of the embodiment 1-4 that measures in 900 milliliters of 0.06N hydrochloric acid distributes and sees the following form 3.These demonstrations that distribute, medicine discharged in 4-12 hour fully.
With 50rpm, 37 ℃ ± 0.5 ℃ temperature is at 900 milliliters of 0.06N with USP II type dissolution equipment for table 3
The dissolution of the tablet of the embodiment 1-4 that measures in the hydrochloric acid
| Time (hour) | The % drug release | |||
| Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | |
| 0.5 | 18 | 21 | 22 | -- |
| 1 | 29 | 44 | 24 | 24 |
| 2 | 47 | 73 | 74 | 36 |
| 3 | -- | 92 | 93 | -- |
| 4 | 75 | 98 | 99 | 52 |
| 6 | 95 | 65 | ||
| 8 | 104 | 77 | ||
| 10 | 87 | |||
| 12 | 93 | |||
Embodiment 5 and 6
| Composition | Weight (milligram) | |
| Embodiment 5 | Embodiment 6 | |
| Gabapentin | 900 | 900 |
| Hydroxypropyl emthylcellulose | 100 | 250 |
| Mannitol | 81 | 76 |
| Poloxamer | 12 | 12 |
| Copolyvidone | 12 | 12 |
| Magnesium stearate | 15 | 10 |
| Pulvis Talci | 15 | 10 |
| Amount to | 1135 | 1270 |
Step
A part of hydroxypropyl cellulose and mannitol are mixed with gabapentin, with the purification of aqueous solutions granulation of hydroxypropyl cellulose remainder.Dried particles and screening by size mix with copolyvidone, poloxamer, magnesium stearate and Pulvis Talci, and compacting in flakes.Then these tablets are placed the HDPE bottle of sealing, in 40 ℃ and 75% relative humidity, placed three months.Stability data sees Table 4.
When table 4 stores three months in 40 ℃ and 75% relative humidity (RH)
The stability data of the tablet of embodiment 5
| Lactams content (weight %) | ||
| Embodiment 5 | Embodiment 6 | |
| Initial | 0.021 | 0.141 |
| 3 months/40 ℃ and 75%RH | 1.038 | 2.184 |
Data in the table 1 and 4 point out that clearly gabapentin is incompatible with HPMC.
Though described several concrete form of the present invention, the present invention who obviously can be under the situation that does not deviate from spirit and scope of the invention describes in detail in to literary composition carries out various modifications and combination.Therefore, except the restriction of claims, the present invention is not restrictive.
Claims (26)
1. stable slow releasing tablet by preparation of granules, described granule comprises:
Gabapentin;
Be selected from one or more hydrophilic rate control polymers of hydroxypropyl cellulose, polyvinylpyrrolidone and derivant thereof and polysaccharide glue; With
One or more optional drug excipients.
2. slow releasing tablet as claimed in claim 1 is characterized in that, when storing three months under the condition of described slow releasing tablet at 40 ℃ and relative humidity 75%, the lactams content of described tablet is no more than 0.6% of gabapentin weight.
3. slow releasing tablet as claimed in claim 1 is characterized in that, described tablet provide gabapentin treatment effective plasma level level for up to about 24 hours.
4. slow releasing tablet as claimed in claim 1 is characterized in that, contains the 100-1200 milligram gabapentin of having an appointment in the described tablet.
5. slow releasing tablet as claimed in claim 1 is characterized in that the viscosity of described hydroxypropyl cellulose is about 7-30,000 centipoise.
6. slow releasing tablet as claimed in claim 5 is characterized in that, the viscosity of described hydroxypropyl cellulose is about 4,000-15,000 centipoise.
7. slow releasing tablet as claimed in claim 1 is characterized in that described polyvinylpyrrolidone derivant is selected from the physical mixture of crospovidone, copolyvidone and polyvinylpyrrolidone and polyvinyl acetate.
8. slow releasing tablet as claimed in claim 1 is characterized in that, described polysaccharide glue is selected from guar gum, arabic gum, xanthan gum, locust bean gum, karaya, gum tragacanth or their combination.
9. slow releasing tablet as claimed in claim 1 is characterized in that described drug excipient is selected from diluent, binding agent, lubricant and fluidizer.
10. slow releasing tablet as claimed in claim 1 is characterized in that described granule does not contain hydroxypropyl emthylcellulose.
11. slow releasing tablet as claimed in claim 1 is characterized in that, described tablet also comprises and blended one or more drug excipients of granule.
12. slow releasing tablet as claimed in claim 1, it is characterized in that, be distributed as with 50rpm, 37 ℃ ± 0.5 ℃ temperature record slow releasing tablet in 900 milliliters of 0.06N hydrochloric acid dissolution with USP II type dissolution equipment, at least 90% gabapentin discharged in 4-12 hour.
13. slow releasing tablet as claimed in claim 12 is characterized in that, at least 90% gabapentin discharged in 8-12 hour.
14. a method of making the stable sustained-release tablet, described method comprises:
Make the mixture granulation of gabapentin and one or more hydrophilic rate control polymers with granulation liquid or binder solution, described polymer is selected from hydroxypropyl cellulose; Polyvinylpyrrolidone and derivant thereof and polysaccharide glue or its combination.
Dry these granules;
Dried granules is mixed with one or more drug excipients, form mixture; With
With the mixture compacting in flakes.
15. method as claimed in claim 14 is characterized in that, when storing three months under the condition of described slow releasing tablet at 40 ℃ and relative humidity 75%, the lactams content of described tablet is no more than 0.6% of gabapentin weight.
16. method as claimed in claim 14 is characterized in that, described tablet provide gabapentin treatment effective plasma level level for up to about 24 hours.
17. method as claimed in claim 14 is characterized in that, gabapentin contains about 100-1200 milligram in the described tablet weight.
18. method as claimed in claim 14 is characterized in that, the viscosity of described hydroxypropyl cellulose is about 7-30,000 centipoise.
19. method as claimed in claim 17 is characterized in that, the viscosity of described hydroxypropyl cellulose is about 4,000-15,000 centipoise.
20. method as claimed in claim 14 is characterized in that, described polyvinylpyrrolidone derivant is selected from the physical mixture of crospovidone, copolyvidone and polyvinylpyrrolidone and polyvinyl acetate.
21. method as claimed in claim 14 is characterized in that, described polysaccharide glue is selected from guar gum, arabic gum, xanthan gum, locust bean gum, karaya, gum tragacanth or their combination.
22. method as claimed in claim 14 is characterized in that, described other medicines excipient is selected from diluent, binding agent, lubricant and fluidizer.
23. method as claimed in claim 14 also comprises one or more drug excipients of mixture granulation with gabapentin and one or more hydrophilic rate control polymers.
Provide a kind of slow-releasing tablets of oral medicine 24. a method for the treatment of medical symptom, described method comprise, described slow-releasing tablets of oral medicine is by the preparation of granules that comprises following material: gabapentin; Be selected from one or more hydrophilic rate control polymers of hydroxypropyl cellulose, polyvinylpyrrolidone and derivant thereof and polysaccharide glue; And one or more optional drug excipients.
25. Therapeutic Method as claimed in claim 24 is characterized in that, described medical symptom comprises one or both in epilepsy and the neuropathic pain.
26. Therapeutic Method as claimed in claim 24 is characterized in that, described medical symptom is an epilepsy.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN968/DEL/2003 | 2003-08-05 | ||
| IN968DE2003 | 2003-08-05 |
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| CN1832736A true CN1832736A (en) | 2006-09-13 |
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| CNA2004800224971A Pending CN1832736A (en) | 2003-08-05 | 2004-08-05 | Stable sustained release oral dosage form of gabapentin |
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| WO (1) | WO2005011666A1 (en) |
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| CN110583654A (en) * | 2019-09-18 | 2019-12-20 | 北京农学院 | Plant source nematicide |
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| WO2006077492A1 (en) * | 2005-01-24 | 2006-07-27 | Ranbaxy Laboratories Limited | Sustained release oral dosage forms of gabapentin |
| JP2008536928A (en) * | 2005-04-19 | 2008-09-11 | アルザ・コーポレーシヨン | A combination of tramadol and a substance comprising gabapentin |
| KR100715354B1 (en) | 2005-08-30 | 2007-05-08 | 주식회사 대웅제약 | Stable gabapentin formulations with suppressed generation of lead substances and preparation methods thereof |
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| FR2897267A1 (en) * | 2006-02-16 | 2007-08-17 | Flamel Technologies Sa | MULTIMICROPARTICULAR PHARMACEUTICAL FORMS FOR PER OS ADMINISTRATION |
| CN102908339A (en) * | 2007-11-23 | 2013-02-06 | 格吕伦塔尔有限公司 | Tapentadol compositions |
| WO2011042793A1 (en) * | 2009-10-06 | 2011-04-14 | Micro Labs Limited | Stabilized pharmaceutical composition comprising gabapentin with minimum levels of pharmaceutically acceptable inert excipients |
| WO2013152852A1 (en) * | 2012-04-10 | 2013-10-17 | Alpinia Laudanum Institute Of Phytopharmaceutical Sciences Ag | Wet granulation process and granulate material comprising arabic gum |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6294198B1 (en) * | 1999-08-24 | 2001-09-25 | Purepac Pharmaceutical Co. | Pharmaceutical tablet formulation containing gabapentin with improved physical and chemical characteristics and method of making the same |
| US7056951B2 (en) * | 2000-09-26 | 2006-06-06 | Mutual Pharmaceutical Co., Inc. | Stable solid dosage forms of amino acids and processes for producing same |
| WO2003103634A1 (en) * | 2002-06-07 | 2003-12-18 | Ranbaxy Laboratories Limited | Sustained release oral dosage forms of gabapentin |
-
2004
- 2004-08-05 WO PCT/IB2004/051408 patent/WO2005011666A1/en active Application Filing
- 2004-08-05 CN CNA2004800224971A patent/CN1832736A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102688216A (en) * | 2012-04-16 | 2012-09-26 | 杭州天诚药业有限公司 | Gabapentin tablet and preparation method thereof |
| CN110583654A (en) * | 2019-09-18 | 2019-12-20 | 北京农学院 | Plant source nematicide |
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| Publication number | Publication date |
|---|---|
| WO2005011666A1 (en) | 2005-02-10 |
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