CN104352460A - Gabapentin tablet and preparation method thereof - Google Patents
Gabapentin tablet and preparation method thereof Download PDFInfo
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- CN104352460A CN104352460A CN201410562976.8A CN201410562976A CN104352460A CN 104352460 A CN104352460 A CN 104352460A CN 201410562976 A CN201410562976 A CN 201410562976A CN 104352460 A CN104352460 A CN 104352460A
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Abstract
The invention belongs to the technical field of medicines, and particularly discloses a gabapentin tablet and a preparation method thereof. According to the invention, micro powder treatment is performed on active components of gabapentin and lactose, and polyvidone K30 is added into a recipe to be used as an adhesive for preparing a finished tablet. The gabapentin tablet is prepared according to the method disclosed by the invention, so that the content uniformity of the prepared preparation conforms to the specification, a new selection can be provided for epileptics with different disease characteristics, and the requirements for treating epilepsy and neurologic diseases can be furthest satisfied.
Description
Invention field
The present invention relates to a kind of pharmaceutical preparation for the treatment of epilepsy and preparation method thereof, belong to neurosurgery or department of general surgery's class disease medication, be specifically related to a kind of gabapentin tablets and preparation method thereof.
Background of invention
Gabapentin tablet quality standard is recorded in American Pharmacopeia 32 editions (USP32), goes on the market and widely use in American-European countries, and domestic also have gabapentin sheet to go on the market.This product was epilepsy therapy medicine originally, single drug: be applicable to suffer from simple or the adult of complexity partial seizures and child's (comprise and newly diagnose patient) of more than 12 years old treatment, can with or without secondary generalized seizures; Drug combination: suffer from partial seizures with or without the child of more than 3 years old and 3 years old of secondary generalized seizures and adult.Found that gabapentin had definite curative effect to various neuralgia afterwards, this product existing has become the neuralgic standard pharmaceutical for the treatment of.
First gabapentin sheet is gone on the market by Pfizer, prescription is except active ingredient, adjuvant is made up of corn starch, hyprolose, poloxamer, copolyvidone, magnesium stearate, wherein gabapentin content about 75%, copolyvidone is dry adhesives, and hyprolose is dissolved in as wet granulation binding agent in こ alcohol, for increasing mouldability and the physics Strong degree of slice, thin piece, therefore add more bonding drug, but dissolution rate is reduced.Domestic commercialized product gabapentin sheet, product gabapentin content is about 62%, and In vitro dissolution rate is also slower.US Patent No. 6, 294, the prescription of the gabapentin sheet of 198B1 Gong Kai ー kind high-load and preparation method, its slice, thin piece is containing gabapentin more than 76%, this patent thinks that gabapentin material is the main cause of high content tablets insufficient formability with crystal form existence, therefore adopt spraying semar technique to prepare granule, main purpose improves the physical strength of slice, thin piece, to can yet be regarded as a kind of ideal preparation method, but use spray granulation equipment, equipment requirements is high, the more important thing is: according to United States pharmacopoeia specifications, the stripping in 45 minutes of gabapentin sheet is greater than 80%, and patent is because will increase slice, thin piece intensity, employ relatively large cellulose and make drug particle be embedded in macromolecular material, therefore to product stripping, requirements at the higher level cannot be proposed, in addition, the change of raw material granularity to product physical property is also studied in that patent.Chinese patent discloses (publication number: CN1720025A)-kind of wet granulation method, be primarily characterized in that some adhesive first adds in medicated powder in solid form, again by remaining binding agent granulation liquid, carry out pelletizing press sheet, though solve wet granulation subproblem, but its adjuvant used is more, in finished product, gabapentin content is also lower, vitro Drug stripping is not very good yet, its method in essence with repeatedly wet granulation zero difference (just first some adhesive dry method being added); The preparation method of Chinese patent discloses (publication number: CN1321083A) a kind of gabapentin coated granule and application thereof, relate to the gabapentin sheet with the disclosure patented method pelletizing press sheet, although there is extraordinary dissolution in vitro, but maximum not enough tablet Chinese traditional medicine content is very few, and application accessory too much (being greater than 45%), it is very inconvenient to use, and does not meet the requirement of modern medicinal agents " three is little ", " three convenience ", and the stability of medicine also may be caused to change.
Because gabapentin safety is good, drug use dosage large (maximum consumption per day can reach 2.4g), as adjuvant in product is too many, patient tolerability certainly will be caused to be deteriorated; Again according to reported in literature, comparatively enteral stripping absorption is more desirable in the outer stripping of intestinal for gabapentin.Therefore Ti Gong ー kind gabapentin content is high, physical strength good, In Vitro Dissolution fast (0.06N hydrochloric acid), to prepare easy gabapentin sheet be necessary.
But existing document is all unexposed comprises gabapentin 10 ~ 30%, filler 50% ~ 98%, binding agent 2% ~ 6%, and the gabapentin sheet pharmaceutical preparation of lubricant 0.5% ~ 2%, do not provide any prompting about its pharmaceutical preparation component ratio yet.
The present invention is by studying for a long period of time, find to adopt gabapentin and lactose with after certain proportion micropowder, can significantly improve the dissolution of insoluble drug gabapentin, and in prescription, the ratio of newborn sugar and starch, the dissolution of concentration on gabapentin sheet of PVP K30 aqueous solution there is appreciable impact.The gabapentin sheet uniformity of dosage units adopting method disclosed by the invention to prepare conforms with the regulations, and prescription composition, disintegration, disintegration phenomenon and dissolved corrosion all with former triturate-cause.
Drafting due to many pH value stripping curve has become the important means dissecting and express solid preparation interior quality, therefore to the scientific evaluation ever more important that stripping curve compares.So far, report has multiple comparative approach.But after " the similar factors relative method " adopting one of model non-dependent method is assert by the official mission of the states such as the U.S. and Japan, now substantially adopted by unified.This method feature carries out the overall evaluation to stripping curve, by calculating similar factors (f
2) compare the similarity of dissolved corrosion.
Computing formula:
R
tand T
trepresent the average accumulated dissolution rate of two preparations when the n-th sample point respectively.
Time point interval selected during calculating is without the need to equal, but two time points that preparation is got must be consistent; And computation time, point should be no less than 3; Because this result of calculation has the characteristic depending on and compare time point number, therefore the time point more than dissolution rate 85% (adjusting release formulation more than 80%) answers no more than one.
Suggestion researcher can according to the concrete condition of reference preparation dissolution rate, and 4 ~ 5 (as adjusting release formulation to can be 4 ~ 6, not advising more than 7 points) time points choosing dissolution rate interval close calculate.
Usually, f is worked as
2between 50-100, numerical value thinks that two stripping curves are similar.
Summary of the invention
The invention provides a kind of pharmaceutical formulation and preparation method of gabapentin sheet, concrete technical scheme is as follows:
On the one hand, the invention provides a kind of gabapentin tablets, wherein, described preparation comprises the component of following weight percentage ratio: gabapentin 10 ~ 30%, filler 50% ~ 98%, binding agent 2% ~ 6%, and lubricant 0.5% ~ 2%.
Some embodiments wherein, gabapentin tablets of the present invention, wherein, described filler is lactose, starch or its combination, and described binding agent is PVP K30 (PVP K30), and described lubricant is magnesium stearate.
Some embodiments wherein, gabapentin tablets of the present invention, wherein, the ratio of described filler breast sugar and starch is 8:1 ~ 2.5:1, described binding agent PVP K30 to be concentration be 12% ~ 20% aqueous solution.
Some embodiments wherein, gabapentin tablets of the present invention, is characterized in that described gabapentin and lactose are for subsequent use after ratio micropowder with 1:20.
Some embodiments wherein, gabapentin tablets of the present invention, it comprises following component:
Some embodiments wherein, gabapentin tablets of the present invention, it comprises following component:
On the other hand, the invention provides a kind of preparation method of gabapentin tablet preparation, wherein, gabapentin and a certain proportion of lactose micropowder, for subsequent use; Prepare certain density PVP K30 aqueous solution, for subsequent use; Take the gabapentin of recipe quantity, lactose, starch mix homogeneously, add PVP K30 aqueous solution and granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.
Gabapentin sheet prepared by the present invention has following advantage: 1, its uniformity of dosage units meets the requirements; 2, its complete disintegrate in 5min.
Carrier of the present invention comprises, but be not limited to, ion-exchanger, aluminum, aluminium stearate, lecithin, serum albumin, as human albumin, buffer substance is as phosphate, glycine, sorbic acid, potassium sorbate, the partial glyceride mixtures of saturated vegetable fatty acid, water, salt or electrolyte, as protamine sulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, colloidal silicon, magnesium trisilicate, polyvinylpyrrolidone, polyacrylate, wax, polyethylene-polyoxypropylene-blocking-up polymer, lanoline, sugar, as lactose, dextrose plus saccharose, starch is as corn starch and potato starch, cellulose and its derivant as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate, natural gum powder, Fructus Hordei Germinatus, gelatin, Pulvis Talci, adjuvant is as cocoa butter and suppository wax, oily as Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, safflower oil, Oleum Sesami, olive oil, Semen Maydis oil and Oleum Glycines, glycol compound, as propylene glycol and Polyethylene Glycol, esters is as ethyl oleate and Ethyl Lauroyl acid esters, agar, buffer agent is as magnesium hydroxide and aluminium hydroxide, alginic acid, pyrogen-free water, isotonic salt, Lin Ge (family name) solution, ethanol, phosphate buffer solution, and other nontoxic proper lubrication agent are as sodium laurylsulfate and magnesium stearate, coloring agent, releasing agent, coating agents, sweeting agent, flavoring agent and spice, antiseptic and antioxidant.
Detailed description of the invention
The detailed description of the invention of form by the following examples, is described in further detail foregoing of the present invention.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following examples.
Embodiment 1
Gabapentin sheet is prepared by following Pharmaceutical ingredients:
Preparation method
Gabapentin and lactose are with the ratio micropowder of 1:20, for subsequent use; Compound concentration is the PVP K30 aqueous solution of 15%, for subsequent use; Take the gabapentin of recipe quantity, lactose, starch mix homogeneously, add PVP K30 aqueous solution and granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.
The gabapentin sheet of preparation has following characteristics:
Content uniformity test: qualified.Disintegration checks: disintegrate completely in 5min, disintegration phenomenon is identical together with former development.
Embodiment 2
Gabapentin sheet is prepared by following Pharmaceutical ingredients:
Preparation method
Gabapentin and lactose are with the ratio micropowder of 1:20, for subsequent use; Compound concentration is the PVP K30 aqueous solution of 15%, for subsequent use; Take the gabapentin of recipe quantity, lactose, starch mix homogeneously, add PVP K30 aqueous solution and granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.
The gabapentin sheet of preparation has following characteristics: Content uniformity test: qualified.Disintegration checks: disintegrate completely in 5min.
Embodiment 3
Gabapentin sheet is prepared by following Pharmaceutical ingredients:
Preparation method
Gabapentin and lactose are with the ratio micropowder of 1:20, for subsequent use; Compound concentration is the PVP K30 aqueous solution of 15%, for subsequent use; Take the gabapentin of recipe quantity, lactose, starch mix homogeneously, add PVP K30 aqueous solution and granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.
The gabapentin sheet of preparation has following characteristics: Content uniformity test: qualified.Disintegration checks: disintegrate completely in 5min.
Various embodiments of the present invention and reference preparation (commercially available ordinary tablet, Hainan Sai Like Pharmaceutical, specification: 300mg) the concrete numerical value of stripping curve see attached list 1.
Table 1 embodiment of the present invention sample stripping curve value
As seen from the above table, gabapentin tablets provided by the present invention, dissolution is obviously better than commercially available ordinary tablet, and stripping curve is comparatively steady, has the effect for the treatment of epilepsy preferably.
The quality stability of gabapentin sheet compares
Gabapentin sheet accelerated test: place six months under the gabapentin sheet (embodiment 1) of blister package being put the condition of temperature 40 DEG C ± 2 DEG C, relative humidity 75% ± 5%, outcome quality is stablized, and indices is as shown in table 2.
Table 2 gabapentin dispersible tablet six months accelerated test testing results
| Inspection batch | Outward appearance | Disintegration (second) | Dispersing uniformity | Dissolution % | Content % |
| Batch 1 | White is smooth | 38 | Conform with the regulations | 98.7 | 99.98 |
| Batches 2 | White is smooth | 40 | Conform with the regulations | 97.9 | 99.96 |
| Batches 3 | White is smooth | 39 | Conform with the regulations | 98.4 | 99.98 |
Claims (7)
1. a gabapentin tablets, wherein, described preparation comprises the component of following weight percentage ratio: gabapentin 10 ~ 30%, filler 50% ~ 98%, binding agent 2% ~ 6%, and lubricant 0.5% ~ 2%.
2. gabapentin tablets according to claim 1, wherein, described filler is lactose, starch or its combination, and described binding agent is PVP K30 (PVP K30), and described lubricant is magnesium stearate.
3. gabapentin tablets according to claim 2, wherein, the ratio of described filler breast sugar and starch is 8:1 ~ 2.5:1, described binding agent PVP K30 to be concentration be 12% ~ 20% aqueous solution.
4. gabapentin tablets according to claim 2, is characterized in that described gabapentin and lactose are for subsequent use after ratio micropowder with 1:20.
5. gabapentin tablets according to claim 2, it comprises following component:
6. gabapentin tablets according to claim 2, it comprises following component:
7. a preparation method for the gabapentin tablets according to any one of claim 1-6, wherein, gabapentin and a certain proportion of lactose micropowder, for subsequent use; Prepare certain density PVP K30 aqueous solution, for subsequent use; Take the gabapentin of recipe quantity, lactose, starch mix homogeneously, add PVP K30 aqueous solution and granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410562976.8A CN104352460A (en) | 2014-10-21 | 2014-10-21 | Gabapentin tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410562976.8A CN104352460A (en) | 2014-10-21 | 2014-10-21 | Gabapentin tablet and preparation method thereof |
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| CN104352460A true CN104352460A (en) | 2015-02-18 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4183771A4 (en) * | 2020-07-20 | 2024-04-24 | Sichuan Haisco Pharmaceutical Co Ltd | Sustained-release pharmaceutical formulation of fused tricyclic gamma-amino acid derivative and preparation method therefor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1449750A (en) * | 2003-05-12 | 2003-10-22 | 徐州恩华药业集团有限责任公司 | Gabapentin slow -released composition |
| WO2004032905A1 (en) * | 2002-10-08 | 2004-04-22 | Ranbaxy Laboratories Limited | Gabapentin tablets and methods for their preparation |
| CN1921839A (en) * | 2004-01-19 | 2007-02-28 | 兰贝克赛实验室有限公司 | Stable sustained-release oral dosage forms of gabapentin and process for preparation thereof |
| CN101120929A (en) * | 2006-08-07 | 2008-02-13 | 珠海天翼医药技术开发有限公司 | Gabapentin stomach retention sustained-release composition |
-
2014
- 2014-10-21 CN CN201410562976.8A patent/CN104352460A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004032905A1 (en) * | 2002-10-08 | 2004-04-22 | Ranbaxy Laboratories Limited | Gabapentin tablets and methods for their preparation |
| CN1449750A (en) * | 2003-05-12 | 2003-10-22 | 徐州恩华药业集团有限责任公司 | Gabapentin slow -released composition |
| CN1921839A (en) * | 2004-01-19 | 2007-02-28 | 兰贝克赛实验室有限公司 | Stable sustained-release oral dosage forms of gabapentin and process for preparation thereof |
| CN101120929A (en) * | 2006-08-07 | 2008-02-13 | 珠海天翼医药技术开发有限公司 | Gabapentin stomach retention sustained-release composition |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4183771A4 (en) * | 2020-07-20 | 2024-04-24 | Sichuan Haisco Pharmaceutical Co Ltd | Sustained-release pharmaceutical formulation of fused tricyclic gamma-amino acid derivative and preparation method therefor |
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Application publication date: 20150218 |
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