CN1709268A - Adefovir dipivoxil orally disintegrating tablet and its preparing method - Google Patents
Adefovir dipivoxil orally disintegrating tablet and its preparing method Download PDFInfo
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- CN1709268A CN1709268A CN 200510075288 CN200510075288A CN1709268A CN 1709268 A CN1709268 A CN 1709268A CN 200510075288 CN200510075288 CN 200510075288 CN 200510075288 A CN200510075288 A CN 200510075288A CN 1709268 A CN1709268 A CN 1709268A
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- adefovir ester
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Abstract
The present invention relates to an Adfuweizhi oral disintegrant tablet and its preparation method. Its basic prescription composition is as follows: according to actual requirement said prescription composition can be regulated and deleted, its composition includes (by wt%) 2-20% of Adfuweizhi, 10-60% of filling agent, 5-30% of disintegrant agent, 2-20% of effervescent agent, 1-15% of corrective agent, 3-20% of metarchon agent, 1-5% of adhesive agent and 0.5-5% of lubricating agent.
Description
Technical field
The present invention relates to medicine of a kind of taking convenience and preparation method thereof, particularly be preparation method and the application thereof that is used for the treatment of the adefovir dipivoxil orally disintegrating tablet of various hepatitis.
Background technology
Present global hepatitis B patient has reached 3.7 hundred million people, and main patient is distributed in states such as the south east asia in Asia, Oceania and Africa.Almost there are every year 1000000 people to die from this disease relevant disease.The chronic HBV carrier has 1.2 hundred million in the population of China, and chronic hepatitis patient has 3,400 ten thousand, and dying from the hepatitis B relevant disease every year has 270,000, and wherein hepatocarcinoma has 150,000 more than.The medicine of hepatitis B mainly is interferon and nucleic acid analog lamivudine.The interferon shortcoming is that response rate is low, can produce temporary hepatopathy and increase the weight of, be unsuitable for seriously carrying out hepatopathy and reach with other internal diseases (infection, immunosuppressant) patient, and, its medical expense height.Lamivudine is the new nucleotide class antiviral agents of Glaxo exploitation, it can suppress duplicating of hepatitis B virus DNA rapidly, improve liver histological, convenient oral, light side-reaction has been comprised that 5 state approvals of China use, but this product major defect is easily recurrence after the drug withdrawal, and can cause the hepatitis B virus variation, produce drug resistance.
Adefovir ester is the prodrug of adenine phosphate compound adefovirdipivoxil, and its molecular formula is C20H32N5O8P, and molecular weight is 501.48.After oral, be converted into adefovirdipivoxil performance antivirus action in vivo.Adefovirdipivoxil is the nucleotide analog of single adenosine phosphate, be phosphorylated to the diphosphonic acid adefovirdipivoxil with active function by the cell kinase effect in vivo, the diphosphonic acid adefovirdipivoxil suppresses HBV DNA polymerase or the reverse transcriptase mechanism of action comprises: (1) competition deoxyadenosine triphosphate substrate; (2) stop viral dna chain elongation.External clinical research data shows that adefovirdipivoxil can suppress duplicating of hbv dna effectively, and hbv dna titre is reduced rapidly, and adefovirdipivoxil can suppress variant with remaining valid in the patient of lamivudine resistance occurring.
Oral cavity disintegration tablet is a kind of new pharmaceutical dosage forms, English " Orally disintegratingtables " by name.U.S. FDA has been ratified this dosage form listing, and reason is: make things convenient for part crowd medication, as the patient's medication under old man, child, dysphagia or the special environment.
Oral cavity disintegration tablet definition: be that a kind of water that do not need in the oral cavity can disintegrate or dissolved tablet.Specification requirement: 1. should be in the oral cavity rapidly disintegrate, no grittiness, good mouthfeel, swallow easily, to the oral mucosa nonirritant.Should stipulate under the character item in the quality standard: disintegrate rapidly, no grittiness, good mouthfeel in the oral cavity; 2. set up suitable disintegration time mensuration method and limit, and be incorporated into standard; 3. to insoluble medicine, should set up suitable dissolution determination method and limit; 4. other should meet general rule requirement under the tablet item.
The characteristics of oral cavity disintegration tablet: 1. absorption is fast, bioavailability is high; 2. instructions of taking does not need water 3. intestinal is residual few, few side effects; 4. avoid the first pass effect of liver sausage.
This medicine has had dosage forms such as soft capsule, drop pill, dispersible tablet, enteric coated preparation to apply for a patent, but the relevant report and the documents and materials of not seeing oral cavity disintegration tablet at present.
Summary of the invention
The poorly water-soluble of adefovir ester, the taste hardship, the bioavailability of common peroral dosage form is lower, disintegration of tablet is slow, the purpose of this invention is to provide a kind of disintegrate fast, absorb rapidly, can effectively improve bioavailability of medicament and blood drug level, improve adefovir ester peroral dosage form-adefovir dipivoxil orally disintegrating tablet of bitterness, taking convenience, few side effects and preparation method thereof simultaneously.
Adefovir dipivoxil orally disintegrating tablet of the present invention also contains adjuvant except principal agent, by weight percentage, be the 2-20% adefovir ester, the adjuvant of 80-98%.Adjuvant is any available adjuvant that is fit to make oral cavity disintegration tablet, and they can comprise filler, disintegrating agent, effervescent, correctives or odor mask, binding agent, lubricant etc.
Because oral cavity disintegration tablet requires disintegrate rapidly in the oral cavity, good mouthfeel, to the oral mucosa nonirritant.Therefore the selection to supplementary product kind and performance thereof is the key of preparation oral cavity disintegration tablet.
The present invention is through selecting, found the pharmaceutic adjuvant of suitable adefovir dipivoxil orally disintegrating tablet, wherein filler selects to be used for increasing the weight and volume of oral cavity disintegration tablet, so that the molding of preparation and divided dose, filler preferably is selected from one or more the mixture in lactose, mannitol, pregelatinized Starch, sorbitol, the xylitol etc. among the present invention.
The kind of disintegrating agent and the selection of consumption are for can this preparation disintegrate be most important fully at the appointed time.Disintegrating agent of the present invention one of is selected to comprise in low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, corn starch, carboxymethylcellulose calcium, the carboxymethyl starch sodium or wherein several mixture.
In oral cavity disintegration tablet, can add some effervescents in right amount, help the disintegrate of tablet, and an amount of acid can also be regulated taste.Acid source is selected from one or more the mixture in citric acid, tartaric acid, four caproic acids, lysine, the arginine in the effervescent that the present invention selects, or alkali source is selected from one or more mixture wherein such as sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate.
When the percentage by weight of principal agent in preparation is higher, owing to bitterness may occur, therefore can select to add an amount of odor mask so that the patient accepts and takes, odor mask of the present invention comprises one or more the mixture in acrylic resin copolymer, Magnesiumaluminumsilicate, gelatin, melon glue, arabic gum, xanthan gum, paraffin, the Brazil wax.
The correctives that the present invention uses one of is selected from Rhizoma et radix valerianae, Fructus Pruni pseudocerasi, Fructus Vitis viniferae, Fructus Citri tangerinae, Fructus Citri Limoniae, Herba Menthae, Fructus Fragariae Ananssae, Fructus Musae, Fructus Ananadis comosi, honey peach essence, maltose alcohol, saccharin sodium, protein sugar, sucrose, Mentholum, aspartame, the stevioside or wherein several mixture.
The adding of binding agent and lubricant is for the ease of the preparation of preparation and molding.Binding agent is selected from one or more the mixture in syrup, starch slurry, carboxymethylcellulose sodium solution, the povidone solution.Lubricant is selected from one or more the mixture in micropowder silica gel, magnesium stearate, the Pulvis Talci.
Oral cavity disintegration tablet of the present invention can be by freeze-drying or direct powder compression or granulating tabletting process preparation.
Adopt freeze-drying to prepare oral cavity disintegration tablet, adjuvant can be chosen filler, disintegrating agent, correctives and odor mask (if necessary), adefovir ester can be mixed with various adjuvants, add the suitable quantity of water dilution, behind the mix homogeneously, place suitable sheet shape mould, lyophilization, being shaped to the material lyophilizing gets final product.
Adopt direct powder compression to prepare oral cavity disintegration tablet, adjuvant can be chosen filler, disintegrating agent, effervescent, lubricant, correctives and odor mask (if necessary), and behind adefovir ester and various adjuvant mix homogeneously, direct powder compression gets final product.
Adopt granulating tabletting process to prepare oral cavity disintegration tablet, adjuvant can be chosen filler, disintegrating agent, binding agent, lubricant, correctives and odor mask (if necessary) with adefovir ester and partial supplementary material mix homogeneously, add binding agent system soft material, granulate, dry, granulate, add the disintegrating agent and the lubricant of surplus, behind the mix homogeneously, tabletting gets final product.
Adopt granulating tabletting process to prepare oral cavity disintegration tablet, adjuvant can be chosen filler, disintegrating agent, effervescent, binding agent, lubricant, correctives and odor mask (if necessary), the main method step is: acid source in the effervescent and alkali source can be separated granulation, or acid source mixed with alkali source, employing contains the dehydrated alcohol binding agent granulates, dry, granulate, the disintegrating agent and the lubricant of adding surplus, behind the mix homogeneously, tabletting gets final product.
Oral cavity disintegration tablet of the present invention, it writes out a prescription composed as follows substantially, can regulate according to actual needs and delete.
| Form | Percentage by weight |
| Aldoforwe ester filler disintegrant effervescent agent flavouring odor mask adhesive lubricant | ????2-20％ ????10-60％ ????5-30％ ????2-20％ ????1-15％ ????3-20％ ????1-5％ ????0.5-5％ |
Wherein filler is selected from one or more the mixture in lactose, mannitol, pregelatinized Starch, sorbitol, the xylitol etc.
Disintegrating agent one of is selected from low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, corn starch, carboxymethylcellulose calcium, the carboxymethyl starch sodium or wherein several mixture.
Acid source is selected from one or more the mixture in citric acid, tartaric acid, four caproic acids, lysine, the arginine in the effervescent, and alkali source is selected from one or more mixture wherein such as sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate.
Odor mask is selected from one or more the mixture in acrylic resin copolymer, Magnesiumaluminumsilicate, gelatin, melon glue, arabic gum, xanthan gum, paraffin, the Brazil wax.
Binding agent is selected from one or more the mixture in syrup, starch slurry, carboxymethylcellulose sodium solution, the povidone solution.
Lubricant is selected from one or more the mixture in micropowder silica gel, magnesium stearate, the Pulvis Talci.
Correctives one of is selected from Rhizoma et radix valerianae, Fructus Pruni pseudocerasi, Fructus Vitis viniferae, Fructus Citri tangerinae, Fructus Citri Limoniae, Herba Menthae, Fructus Fragariae Ananssae, Fructus Musae, Fructus Ananadis comosi, honey peach essence, maltose alcohol, saccharin sodium, protein sugar, sucrose, aspartame, the stevioside or wherein several mixture.
The most preferred prescription composition of the present invention is seen embodiment.
Adopt the technology of the present invention that adefovir ester is prepared into oral cavity disintegration tablet, not only expanded the dosage form range of application of adefovir ester, particularly through selection to the present invention's prescription, it is good to have obtained the sense of taste, disintegrate rapidly, absorb fast, taking convenience, can improve bioavailability of medicament and blood drug level, improve the novel formulation of anti-HBV effect.
The specific embodiment
Come adefovir dipivoxil orally disintegrating tablet of the present invention done further specifying by following example, but be not limited in following example.
Embodiment 1
Prescription:
Adefovir ester 2%
Polyvinylpolypyrrolidone 55%
Microcrystalline Cellulose 30%
Lactose 25%
Sucrose 30%
Saccharin sodium 1%
Eudrgit?L30D????????6.5％
Flavoring orange essence 0.5%
Preparation method:
Adefovir ester is added in the Eudrgit L30D suspension, add suitable quantity of water, after stirring, add polyvinylpolypyrrolidone, microcrystalline Cellulose, lactose, sucrose, saccharin sodium, flavoring orange essence, the limit edged stirs, behind the one-tenth suspension, in perfusion and the suitable moral mould, lyophilization, press seal, packing.
Embodiment 2
Prescription:
Adefovir ester 15%
Mannitol 10%
Pregelatinized Starch 10%
Guar gum 5%
Arabic gum 10%
Xylitol 30%
Microcrystalline Cellulose 19.5%
Fructus Citri Limoniae essence 0.5%
Preparation method:
Adefovir ester is added in guar gum and the arabic gum mixed liquor, after stirring, add mannitol, pregelatinized Starch, xylitol, microcrystalline Cellulose, Fructus Citri Limoniae essence, the limit edged stirs, behind the one-tenth suspension, in perfusion and the suitable moral mould, lyophilization, press seal, packing.
Embodiment 3
Prescription:
Adefovir ester 10%
Gelatin 20%
Xylitol 20%
Microcrystalline Cellulose 40%
Aspartame 4.5%
Crosslinked carboxymethyl fecula sodium 5%
Honey peach essence 0.5%
Preparation method:
Adefovir ester is added in the gelatin solution, after stirring, add xylitol, microcrystalline Cellulose, aspartame, crosslinked carboxymethyl fecula sodium, honey peach essence, the limit edged stirs, behind the one-tenth suspension, in perfusion and the suitable moral mould, lyophilization, press seal, packing.
Embodiment 4
Prescription:
Adefovir ester 8%
Cross-linking sodium carboxymethyl cellulose 5%
Starch 25%
Sorbitol 35%
Stevioside 0.5%
Sucrose 25%
Strawberry essence 0.5%
Micropowder silica gel 1%
Preparation method:
After supplementary materials such as adefovir ester, starch, sorbitol, sucrose, cross-linking sodium carboxymethyl cellulose, strawberry essence, micropowder silica gel are crossed 80 mesh sieves, mix homogeneously, direct powder compression gets final product.
Embodiment 5
Prescription:
Adefovir ester 5%
Magnesiumaluminumsilicate 10%
L-HPC?????????30％
Lactose 11.5%
Mannitol 40%
Protein sugar 1%
Flavoring pineapple essence 1%
Magnesium stearate 1.5%
Preparation method:
To all cross adefovir ester, L-HPC, mannitol, the Magnesiumaluminumsilicate mix homogeneously of 80 mesh sieves, other gets protein sugar, flavoring pineapple essence adopts the equivalent method of progressively increasing to mix with above mixture, adds the magnesium stearate mix homogeneously, and direct powder compression gets final product.
Embodiment 6
Prescription:
Adefovir ester 10%
Mannitol 35%
Microcrystalline Cellulose 30%
Lactose 11.5%
Crospolyvinylpyrrolidone 3%
Sodium bicarbonate 4%
Citric acid 5%
Pulvis Talci 1%
Aspartame 1.5%
Preparation method:
Adefovir ester, microcrystalline Cellulose, mannitol, lactose, sodium bicarbonate, the citric acid mix homogeneously of 80 mesh sieves will all be crossed, other gets crospolyvinylpyrrolidone, aspartame adopts the equivalent method of progressively increasing to mix with above mixture, add the Pulvis Talci mix homogeneously, direct powder compression gets final product.
Embodiment 7
Prescription:
Adefovir ester 8%
CMC-Ca????????????6％
Mannitol 44%
Microcrystalline Cellulose 32%
Aspartame 2.5%
Fructus Citri Limoniae essence 1.0%
Pulvis Talci 1.5%
Starch slurry an amount of (about 5%)
Preparation method:
With all crossing adefovir ester, mannitol, aspartame, Fructus Citri Limoniae essence, the part microcrystalline Cellulose of 80 mesh sieves, with starch slurry system soft material, granulate, dry, granulate, microcrystalline Cellulose, CMC-Ca, the Pulvis Talci of adding surplus, mix homogeneously, tabletting gets final product.
Embodiment 8
Prescription:
Adefovir ester 10%
Microcrystalline Cellulose 15%
Xylitol 30%
Sucrose 15%
Starch 20.5%
Stevioside 1.5%
Cross-linking sodium carboxymethyl cellulose 3.5%
Flavoring orange essence 1.0%
Polyvinylpolypyrrolidone (50 alcoholic solution) 2%
Magnesium stearate 1.5%
Preparation method:
Adefovir ester, xylitol, sucrose, starch, aspartame, flavoring orange essence, the part microcrystalline Cellulose mix homogeneously of 80 mesh sieves will all be crossed, with polyvinylpolypyrrolidone alcohol liquid system soft material, granulate, dry, granulate, the microcrystalline Cellulose, CMC-Na, the magnesium stearate that add surplus, mix homogeneously, tabletting gets final product.
Embodiment 9
Prescription:
Adefovir ester 10%
Xylitol 40%
Microcrystalline Cellulose 20%
Sucrose 14%
Citric acid 3%
Sodium bicarbonate 4%
Herba Menthae essence 1.5%
PVP-K30 (dehydrated alcohol) 5%
CMS-Na?????????????????????1.5％
Pulvis Talci 1%
Preparation method:
With all crossing adefovir ester, sucrose, microcrystalline Cellulose, citric acid, the sodium bicarbonate mix homogeneously of 80 mesh sieves, with PVP-K30 anhydrous alcohol solution system soft material, to granulate, dry, granulate add CMS-Na, Pulvis Talci, mix homogeneously, tabletting gets final product.
Embodiment 10
Prescription:
Adefovir ester 10%
Mannitol 32.5%
Microcrystalline Cellulose 40%
Low-replacement hydroxypropyl cellulose 3%
Sodium carbonate 4%
Sodium bicarbonate 0.5%
Tartaric acid 5.5%
Aspartame 2%
Magnesium stearate 1.5%
Micropowder silica gel 1.0%
Preparation method:
To all cross adefovir ester, microcrystalline Cellulose, sodium bicarbonate, the sodium carbonate mix homogeneously of 80 mesh sieves,, granulate dry, granulate with L-HPC50% ethanol liquid system soft material; Other gets mannitol, adds tartaric acid, and mix homogeneously with L-HPC50% ethanol liquid system soft material, is granulated, and dry, granulate behind two kinds of granule mix homogeneously, add aspartame, magnesium stearate, micropowder silica gel outward, and tabletting behind the mix homogeneously gets final product.
Claims (10)
1, a kind of adefovir dipivoxil orally disintegrating tablet contains adefovir ester active component and the excipient substance that is fit to make oral cavity disintegration tablet, and wherein the percentage by weight of adefovir ester is 2-20%, and the percentage by weight of adjuvant is 80-98%.
2, the described oral cavity disintegration tablet of claim 1 is characterized in that, the described excipient substance that is fit to make oral cavity disintegration tablet is selected from filler, disintegrating agent, effervescent, correctives, odor mask, binding agent or lubricant.
3, the described oral cavity disintegration tablet of claim 2 is characterized in that, it is composed as follows to fill a prescription:
Adefovir ester 2-20%
Filler 10-60%
Disintegrating agent 5-30%
Effervescent 2-20%
Correctives 1-15%
Odor mask 3-20%
Binding agent 1-5%
Lubricant 0.5-5%.
4, the described oral cavity disintegration tablet of claim 3 is characterized in that described filler is selected from one or more the mixture in lactose, mannitol, pregelatinized Starch, sorbitol, the xylitol; Described disintegrating agent is selected from a kind of or wherein several mixture in low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, corn starch, carboxymethylcellulose calcium, the carboxymethyl starch sodium; Acid source is selected from one or more the mixture in citric acid, tartaric acid, four caproic acids, lysine, the arginine in the described effervescent, and alkali source is selected from one or more mixture wherein such as sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate; Described odor mask is selected from one or more the mixture in acrylic resin copolymer, Magnesiumaluminumsilicate, gelatin, melon glue, arabic gum, xanthan gum, paraffin, the Brazil wax; Described binding agent is selected from one or more the mixture in syrup, starch slurry, carboxymethylcellulose sodium solution, the povidone solution; Described lubricant is selected from one or more the mixture in micropowder silica gel, magnesium stearate, the Pulvis Talci; Described correctives one of is selected from Rhizoma et radix valerianae, Fructus Pruni pseudocerasi, Fructus Vitis viniferae, Fructus Citri tangerinae, Fructus Citri Limoniae, Herba Menthae, Fructus Fragariae Ananssae, Fructus Musae, Fructus Ananadis comosi, honey peach essence, maltose alcohol, saccharin sodium, protein sugar, sucrose, aspartame, the stevioside or wherein several mixture.
5, the described oral cavity disintegration tablet of claim 3 is characterized in that, it is composed as follows to fill a prescription:
Adefovir ester 2%
Polyvinylpolypyrrolidone 55%
Microcrystalline Cellulose 30%
Lactose 25%
Sucrose 30%
Saccharin sodium 1%
Eudrgit?L30D??????????????6.5％
Flavoring orange essence 0.5%
Aspartame 1.5%.
6, the described oral cavity disintegration tablet of claim 3 is characterized in that, it is composed as follows to fill a prescription:
Adefovir ester 5%
Magnesiumaluminumsilicate 10%
L-HPC?????????????????????30％
Lactose 11.5%
Mannitol 40%
Protein sugar 1%
Flavoring pineapple essence 1%
Magnesium stearate 1.5%.
7, the described oral cavity disintegration tablet of claim 3 is characterized in that, it is composed as follows to fill a prescription:
Adefovir ester 10%
Microcrystalline Cellulose 15%
Xylitol 30%
Sucrose 15%
Starch 20.5%
Stevioside 1.5%
Cross-linking sodium carboxymethyl cellulose 3.5%
Flavoring orange essence 1.0%
Polyvinylpolypyrrolidone (50 alcoholic solution) 2%
Magnesium stearate 1.5%.
8, the described oral cavity disintegration tablet of claim 3 is characterized in that, it is composed as follows to fill a prescription:
Adefovir ester 10%
Mannitol 35%
Microcrystalline Cellulose 30%
Lactose 11.5%
Crospolyvinylpyrrolidone 3%
Sodium bicarbonate 4%
Citric acid 5%
Pulvis Talci 1%.
9, the preparation method of the oral cavity disintegration tablet of claim 1, it is characterized in that, adopt the preparation of freeze-drying or direct powder compression or granulating tabletting process, wherein the preparation process of freeze-drying is: adefovir ester and filler, disintegrating agent, correctives and odor mask are added the suitable quantity of water dilution, behind the mix homogeneously, place suitable sheet shape mould, lyophilization is shaped to the material lyophilizing; Wherein the direct powder compression preparation process is: behind adefovir ester and filler, disintegrating agent, effervescent, lubricant, correctives and odor mask mix homogeneously, and direct powder compression; Wherein the granulating tabletting process preparation process is: with adefovir ester and partially filled dose, disintegrating agent, correctives and odor mask, add binding agent system soft material, granulate, and dry, granulate, the disintegrating agent and the lubricant of adding surplus, behind the mix homogeneously, tabletting.
10, the described preparation method of claim 9, it is characterized in that, the step that wherein adds effervescent is, acid source in the effervescent and alkali source are separated granulation, or acid source is mixed with alkali source, adopt to contain the granulation of dehydrated alcohol binding agent, dry, granulate, the disintegrating agent and the lubricant that add surplus, behind the mix homogeneously, tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510075288 CN1709268A (en) | 2005-06-10 | 2005-06-10 | Adefovir dipivoxil orally disintegrating tablet and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510075288 CN1709268A (en) | 2005-06-10 | 2005-06-10 | Adefovir dipivoxil orally disintegrating tablet and its preparing method |
Publications (1)
| Publication Number | Publication Date |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152190B (en) * | 2006-09-29 | 2010-06-23 | 北京德众万全药物技术开发有限公司 | Orally disintegrating tablets of adefovir dipivoxil and method for preparing the same |
| CN101138554B (en) * | 2006-09-05 | 2010-09-29 | 云南白药集团股份有限公司 | Effervescence dispersible tablet |
-
2005
- 2005-06-10 CN CN 200510075288 patent/CN1709268A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101138554B (en) * | 2006-09-05 | 2010-09-29 | 云南白药集团股份有限公司 | Effervescence dispersible tablet |
| CN101152190B (en) * | 2006-09-29 | 2010-06-23 | 北京德众万全药物技术开发有限公司 | Orally disintegrating tablets of adefovir dipivoxil and method for preparing the same |
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Open date: 20051221 |