CN101152190B - Orally disintegrating tablets of adefovir dipivoxil and method for preparing the same - Google Patents
Orally disintegrating tablets of adefovir dipivoxil and method for preparing the same Download PDFInfo
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- CN101152190B CN101152190B CN 200610113482 CN200610113482A CN101152190B CN 101152190 B CN101152190 B CN 101152190B CN 200610113482 CN200610113482 CN 200610113482 CN 200610113482 A CN200610113482 A CN 200610113482A CN 101152190 B CN101152190 B CN 101152190B
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- orally disintegrating
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Abstract
The invention discloses an adefovir dipivoxil orally disintegrating tablet and the preparation method. The orally disintegrating tablet contains active component adefovir dipivoxil, sweetenersucralose and other pharmaceutically acceptable excipients, and is prepared in freeze-drying method, powder pressing method, granulating and tabletting method. The orally disintegrating tablet has the advantages of good taste, easy administration and is used to treat chronic hepatitis B.
Description
Technical field
The present invention relates to a kind of taking convenience the treatment chronic hepatitis B the prescription of adefovir dipivoxil orally disintegrating tablet improve and preparation method thereof.
Background technology
Present global hepatitis B patient has reached 3.7 hundred million people, and having every year almost, 1,000,000 patients die from this disease relevant disease.Chronic viral hepatitis B virus carrier has 1.2 hundred million in the population of China, and chronic hepatitis patient has 3,400 ten thousand, and the patient who dies from this disease relevant disease every year has 270,000.
Adefovir ester is the prodrug of adenine phosphate compound adefovirdipivoxil, oral after, be converted into adefovirdipivoxil performance antivirus action in vivo.According to present basis and clinical research data about adefovirdipivoxil, adefovirdipivoxil can suppress HBV DNA effectively, and the variant of lamivudine resistance also there is the obvious suppression effect, adefovirdipivoxil drug resistance correlated virus variation incidence rate is lower, therefore it is an effective hepatitis B virus resisting medicine, has broad application prospects.
Disclose a kind of adefovir dipivoxil orally disintegrating tablet and preparation method thereof among the CN 1709268A, disclose the application in adefovir dipivoxil orally disintegrating tablet of saccharin sodium, sucrose, protein sugar (aspartame) and stevioside as sweeting agent.
Have been found that, adopt the disclosed saccharin sodium of CN 1709268A to have 25% people and metallic taste is arranged taking aftersensation, protein sugar is an aspartame, sugariness is 180～200 times of sucrose, it and magnesium stearate have incompatibility, and reported once that the side effect that overdose causes was more, comprising: headache, epilepsy grand mal, the loss of memory, gastrointestinal reaction and skin symptom.The sugariness of sucrose is low, and is unfavorable for that diabetes patient and other take the bad disease patient of carbohydrate metabolism.The sugariness of stevioside is 200 times of sucrose, and countries in the world are disputable always to the use of stevioside, and U.S. FDA 3 refusal approvals think that with the application of stevioside as food additive its safety does not also obtain to confirm fully.
Therefore, be necessary to provide a kind of new Orally disintegrating pharmaceutical composition that contains adefovirdipivoxil, overcome the defective that technical scheme that CN1709268A provides exists.
Summary of the invention
The purpose of this invention is to provide a kind of adefovir dipivoxil orally disintegrating tablet, not only disintegrate is rapid for it, is beneficial to absorption, and onset is faster, and mouthfeel is better, takes safer.
The oral cavity disintegration tablet that contains adefovir ester, sucralose provided by the invention can adopt freeze-drying, powder pressing method, granulating tabletting process preparation.
The oral cavity disintegration tablet that contains adefovir ester, sucralose provided by the invention contains adefovir ester and accounts for 5%～20% weight portion, and sucralose accounts for 0.08%～0.2% weight portion.
Adefovir dipivoxil orally disintegrating tablet provided by the invention also contains a kind of and/or several mixture in filler, excipient, binding agent, disintegrating agent, the lubricant as being fit to adjuvant of the present invention.
Adefovir dipivoxil orally disintegrating tablet provided by the invention can be selected from a kind of and/or several mixture in mannitol, sorbitol, xylitol, starch, the microcrystalline Cellulose as being fit to filler of the present invention.
Adefovir dipivoxil orally disintegrating tablet provided by the invention can be selected from a kind of and/or several mixture in mannitol, sorbitol, the xylitol as being fit to excipient of the present invention.
Adefovir dipivoxil orally disintegrating tablet provided by the invention is as the optional a kind of and/or several mixture in polyvidone, sodium carboxymethyl cellulose, starch slurry, pregelatinized Starch slurry, gelatin, xanthan gum, different concentration ethanol, water of suitable binding agent of the present invention.
Adefovir dipivoxil orally disintegrating tablet provided by the invention can be selected from a kind of and/or several mixture in polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, the low-substituted hydroxypropyl cellulose as being fit to disintegrating agent of the present invention.
Adefovir dipivoxil orally disintegrating tablet provided by the invention can be selected from a kind of and/or several mixture in magnesium stearate, micropowder silica gel, the Pulvis Talci as being fit to lubricant of the present invention.
The preparation method of adefovir dipivoxil orally disintegrating tablet can be that freeze-drying, powder pressing method, granulating tabletting process are prepared, and concrete method for making is as follows:
Freeze-drying: component comprises adefovir ester active component and adjuvant, adjuvant comprises excipient and sucralose, the percentage by weight of adefovir ester is 5%～20%, and the percentage by weight of sucralose is 0.08%～0.2%, and the percentage by weight of excipient is 78.8%～94.92%.The main method step is: after adefovir ester and excipient and sucralose were added suitable quantity of water dilution, mix homogeneously placed suitable sheet shape mould, puts into the freezer dryer lyophilization, was shaped to the material bone dry.
Powder pressing method: component comprises adefovir ester active component and adjuvant, adjuvant comprises sucralose and a kind of and/or several mixture that contains in filler, disintegrating agent, the lubricant, the percentage by weight of adefovir ester is 5%～20%, the percentage by weight of sucralose is 0.08%～0.2%, and the percentage by weight summation of other adjuvant is 78.8%～94.92%.The main method step is: with adefovir ester and sucralose and other adjuvant mix homogeneously, be shaped with suitable punch die tabletting.
Granulating tabletting process comprises compressing dry granulation and wet granule compression tablet method, the step of compressing dry granulation is: component comprises adefovir ester active component and adjuvant, adjuvant comprises sucralose and a kind of and/or several mixture that contains in filler, disintegrating agent, the lubricant, the percentage by weight of adefovir ester is 5%～20%, the percentage by weight of sucralose is 0.08%～0.2%, and the percentage by weight summation of other adjuvant is 78.8%～94.92%.The main method step is: with adefovir ester and sucralose and filler, disintegrating agent mix homogeneously, behind dry granulation mechanism grain, add mix lubricant and evenly be shaped with suitable punch die tabletting the back.
The step of wet granule compression tablet method is: component comprises adefovir ester active component and adjuvant, adjuvant comprises sucralose and a kind of and/or several mixture that contains in filler, binding agent, disintegrating agent, the lubricant, the percentage by weight of adefovir ester is 5%～20%, the percentage by weight of sucralose is 0.08%～0.2%, and the percentage by weight summation of other adjuvant is 78.8%～94.92%.The main method step is: with adefovir ester and sucralose and filler, disintegrating agent mix homogeneously, add suitable amount of adhesive system soft material, granulate, drying, add behind the granulate residue disintegrating agent and mix lubricant evenly the back with suitable punch die tabletting shaping.
Use the adefovir dipivoxil orally disintegrating tablet of freeze-drying preparation, place lingual surface to dissolve rapidly, the time was less than ten seconds; Use the adefovir dipivoxil orally disintegrating tablet of powder pressing method and granulating tabletting process preparation, based on disintegrate, disintegration time is all less than 40 seconds in the oral cavity, the equal good mouthfeel of all components, and sugariness is suitable, does not have bitter, puckery and grittiness.
The specific embodiment
Below in conjunction with embodiment the present invention is described in further detail, but not only is confined to following embodiment.
Embodiment 1:
Adefovir ester 10%
Mannitol 45%
Lactose 34%
Low-substituted hydroxypropyl cellulose 8%
Fructus Citri Limoniae essence 0.7%
Mentholum 1.2%
Sucralose 0.1%
Magnesium stearate 1%
100％
Preparation method:
With adefovir ester and sucralose and mannitol, lactose, low-substituted hydroxypropyl cellulose, Fructus Citri Limoniae essence mix homogeneously, behind dry granulation mechanism grain, be shaped with 6mm punch die tabletting after adding Mentholum and magnesium stearate mix homogeneously.The heavy 100mg of sheet, disintegration time is 20～30 seconds.
Embodiment 2:
Adefovir ester 10%
Mannitol 89.9%
Sucralose 0.1%
100％
Preparation method:
After adefovir ester and mannitol and sucralose added suitable quantity of water dilution, mix homogeneously placed 8mm sheet shape mould, puts into the freezer dryer lyophilization, to the postforming of material bone dry.The heavy 100mg of sheet, disintegration time is 3～5 seconds.
Embodiment 3:
Adefovir ester 10%
Mannitol 49%
Microcrystalline Cellulose 30%
Low-substituted hydroxypropyl cellulose 8%
Mentholum 1.85%
Sucralose 0.15%
Magnesium stearate 1%
100％
Preparation method:
With adefovir ester and sucralose and mannitol, lactose, low-substituted hydroxypropyl cellulose, Fructus Citri Limoniae essence mix homogeneously; granulate through wet granulator; behind drying, the granulate, be shaped with 6mm punch die tabletting behind adding microcrystalline Cellulose, Mentholum and the magnesium stearate mix homogeneously.The heavy 100mg of sheet, disintegration time is 30～35 seconds.
Comparative example 1 (CN 1709268A embodiment 4):
Adefovir ester 8%
Cross-linking sodium carboxymethyl cellulose 5%
Starch 25%
Sorbitol 35%
Steviosin 0.5%
Sucrose 25%
Strawberry essence 0.5%
Micropowder silica gel 1%
100％
Preparation method:
80 mesh sieves are crossed in adefovir ester, starch, sorbitol, sucrose, cross-linking sodium carboxymethyl cellulose, strawberry essence, micropowder silica gel, and mix homogeneously is shaped with 7mm punch die tabletting.Sheet heavily is 125mg, and disintegration time is 50 seconds.
Comparative example 2 (CN 1709268A embodiment 5):
Adefovir ester 10%
Magnesiumaluminumsilicate 35%
Microcrystalline Cellulose 30%
Lactose 11.5%
Crospolyvinylpyrrolidone 3%
Sodium bicarbonate 4%
Citric acid 5%
Pulvis Talci 1%
Aspartame 1.5%
100％
Preparation method:
Adefovir ester, microcrystalline Cellulose, lactose, sodium bicarbonate, the citric acid mix homogeneously of 80 mesh sieves will be crossed, other gets crospolyvinylpyrrolidone, aspartame and above mixture and adopts the equivalent method mix homogeneously that progressively increases, add the Pulvis Talci mix homogeneously, be shaped with 6mm punch die tabletting.Sheet heavily is 100mg, and disintegration time is 25～35 seconds.
Embodiment 4
Table 1,24 health volunteers take the disintegration time that is subjected to Orally disintegrating behind the test preparation
| Name | Embodiment 1 disintegration time (s) | Embodiment 1 mouthfeel | Comparative example's 1 disintegration time (s) | Comparative example's 1 mouthfeel | Comparative example's 2 disintegration times (s) | Comparative example's 2 mouthfeels |
| WJC | 20 | Well, no grittiness | 50 | Sticking puckery, no grittiness | 26 | Well, grittiness is arranged |
| ZHL | 20 | Well, no grittiness | 52 | Sticking puckery, no grittiness | 42 | Sour and astringent, grittiness is arranged |
| PJY | 25 | Well, no grittiness | 46 | Well, no grittiness | 33 | Sour and astringent, grittiness is arranged |
| LAK | 20 | Well, no grittiness | 44 | Sticking puckery, no grittiness | 30 | Well, grittiness is arranged |
| GBT | 20 | Well, no grittiness | 49 | Sticking puckery, no grittiness | 28 | Well, grittiness is arranged |
| WJL | 30 | Well, no grittiness | 52 | Sticking puckery, no grittiness | 40 | Well, grittiness is arranged |
| Name | Embodiment 1 disintegration time (s) | Embodiment 1 mouthfeel | Comparative example's 1 disintegration time (s) | Comparative example's 1 mouthfeel | Comparative example's 2 disintegration times (s) | Comparative example's 2 mouthfeels |
| ZCJ | 22 | Well, no grittiness | 55 | Well, no grittiness | 41 | Well, grittiness is arranged |
| MYK | 20 | Well, no grittiness | 52 | Sticking puckery, no grittiness | 24 | Well, grittiness is arranged |
| SFJ | 20 | Well, no grittiness | 50 | Sticking puckery, no grittiness | 37 | Sour and astringent, grittiness is arranged |
| JYJ | 20 | Well, no grittiness | 48 | Well, no grittiness | 47 | Well, grittiness is arranged |
| TAW | 15 | Well, no grittiness | 43 | Well, no grittiness | 28 | Sour and astringent, grittiness is arranged |
| JFL | 20 | Well, no grittiness | 38 | Well, no grittiness | 31 | Well, grittiness is arranged |
| TOF | 18 | Well, no grittiness | 58 | Sticking puckery, no grittiness | 31 | Sour and astringent, grittiness is arranged |
| DLY | 15 | Well, no grittiness | 45 | Well, no grittiness | 31 | Well, grittiness is arranged |
| YOT | 25 | Well, no grittiness | 39 | Well, no grittiness | 33 | Well, grittiness is arranged |
| LZQ | 20 | Well, no grittiness | 44 | Well, no grittiness | 41 | Sour and astringent, grittiness is arranged |
| BAW | 25 | Well, no grittiness | 54 | Sticking puckery, no grittiness | 45 | Sour and astringent, grittiness is arranged |
| WHC | 20 | Well, no grittiness | 45 | Well, no grittiness | 20 | Well, grittiness is arranged |
| QYX | 28 | Well, no grittiness | 45 | Well, no grittiness | 46 | Sour and astringent, grittiness is arranged |
| GHL | 25 | Well, no grittiness | 60 | Sticking puckery, no grittiness | 25 | Well, grittiness is arranged |
| DZY | 25 | Well, no grittiness | 58 | Sticking puckery, no grittiness | 22 | Well, grittiness is arranged |
| SYZ | 25 | Well, no grittiness | 49 | Well, no grittiness | 26 | Well, grittiness is arranged |
| LSX | 18 | Well, no grittiness | 48 | Sticking puckery, no grittiness | 18 | Well, grittiness is arranged |
| ZHS | 30 | Well, no grittiness | 33 | Well, no grittiness | 22 | Well, grittiness is arranged |
| Mean ±SD | 22±4 | Well, no grittiness | 48±7 | Slightly sticking puckery, no grittiness | 32±9 | Slightly sour and astringent, grittiness is arranged |
Therefore, from the result shown in the table 1 as can be seen, use the mouthfeel aspect of the system of used prescription of the present invention and prepared to be better than disclosed adefovir dipivoxil orally disintegrating tablet among the CN 1709268A.
Claims (1)
1. oral cavity disintegration tablet that contains adefovir ester; it is characterized in that adefovir ester by (percentage by weight) 10%; 45% mannitol; 34% lactose; 8% low-substituted hydroxypropyl cellulose; 0.7% Fructus Citri Limoniae essence; 1.2% Mentholum; 0.1% sucralose and 1% magnesium stearate are formed; and preparation by the following method: with adefovir ester and sucralose and mannitol; lactose; low-substituted hydroxypropyl cellulose; the Fructus Citri Limoniae essence mix homogeneously; behind dry granulation mechanism grain, be shaped with the punch die tabletting behind adding Mentholum and the magnesium stearate mix homogeneously.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610113482 CN101152190B (en) | 2006-09-29 | 2006-09-29 | Orally disintegrating tablets of adefovir dipivoxil and method for preparing the same |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610113482 CN101152190B (en) | 2006-09-29 | 2006-09-29 | Orally disintegrating tablets of adefovir dipivoxil and method for preparing the same |
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| Publication Number | Publication Date |
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| CN101152190A CN101152190A (en) | 2008-04-02 |
| CN101152190B true CN101152190B (en) | 2010-06-23 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1528273A (en) * | 2003-10-21 | 2004-09-15 | 宇 周 | Analgesic tramadol hydrochloride oral disintegrating tablet and preparing method thereof |
| CN1546046A (en) * | 2003-12-08 | 2004-11-17 | 杨喜鸿 | Adefovir dipivoxil dispersing tablet and its preparation |
| CN1709268A (en) * | 2005-06-10 | 2005-12-21 | 北京阜康仁生物制药科技有限公司 | Adefovir dipivoxil orally disintegrating tablet and its preparing method |
| CN1795857A (en) * | 2004-12-30 | 2006-07-05 | 北京德众万全医药科技有限公司 | Composition for covering flavor and preparation of containing the composition |
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- 2006-09-29 CN CN 200610113482 patent/CN101152190B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1528273A (en) * | 2003-10-21 | 2004-09-15 | 宇 周 | Analgesic tramadol hydrochloride oral disintegrating tablet and preparing method thereof |
| CN1546046A (en) * | 2003-12-08 | 2004-11-17 | 杨喜鸿 | Adefovir dipivoxil dispersing tablet and its preparation |
| CN1795857A (en) * | 2004-12-30 | 2006-07-05 | 北京德众万全医药科技有限公司 | Composition for covering flavor and preparation of containing the composition |
| CN1709268A (en) * | 2005-06-10 | 2005-12-21 | 北京阜康仁生物制药科技有限公司 | Adefovir dipivoxil orally disintegrating tablet and its preparing method |
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| CN101152190A (en) | 2008-04-02 |
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