CN1903208A - Adefovir dipivoxil oral disintegration tablets medicine prepn., and prepn. method therefor - Google Patents
Adefovir dipivoxil oral disintegration tablets medicine prepn., and prepn. method therefor Download PDFInfo
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- CN1903208A CN1903208A CN 200510021349 CN200510021349A CN1903208A CN 1903208 A CN1903208 A CN 1903208A CN 200510021349 CN200510021349 CN 200510021349 CN 200510021349 A CN200510021349 A CN 200510021349A CN 1903208 A CN1903208 A CN 1903208A
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- oral disintegration
- adefovir dipivoxil
- disintegration tablets
- medicine preparation
- adefovir
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Abstract
An oral disintegrating tablet of adefovirdipivoxil ester contains adefovirdipivoxil ester, dispersing solid carrier, filler, disintegrant, flavouring, lubricant and flow aid through wet granulating and tabletting,or direct tabletting. Its preparing process is also disclosed.
Description
Technical field
What the present invention relates to is oral disintegration tablets medicine preparation of a kind of adefovir ester and preparation method thereof.
Background technology
Adefovir ester (adefovir dipivoxil) is the purine analog derivative, be the novel open chain nucleotide of a class, adefovir ester can suppress the activity of the DNA polymerase of HBV, and can penetrate among the DNA of hepatitis B virus, suppress duplicating of virus, lamivudine and the drug-fast HBV Strain of famciclovir all there are very strong inhibitory action, the existing now report of this medicine and using, but what only relate to is the medicine of its conventional tablet dosage form.Because the conventional tablet medicine generally all need be swallowed with help by drinking-water when taking, and can reduce the gastral damage to the people.Therefore, at present this medicine for some as old people, child with there is patient's compliance of dysphagia poor, as go out or the use that lacks under the specific condition such as drinking water also can be subjected to very big restriction.
Summary of the invention
At above-mentioned situation, the present invention will provide a kind of preparation method simple, taking convenience for addressing the above problem, rapid-action to indication, reach the peak early, the tangible adefovir dipivoxil oral disintegration tablets medicine preparation of curative effect, and the preparation method of this pharmaceutical preparation.
Adefovir dipivoxil oral disintegration tablets medicine preparation of the present invention is to be the active drug composition with the adefovir ester, forms jointly with the acceptable auxiliary element of pharmacy.Wherein said auxiliary element is mainly solid dispersion carrier, filler, disintegrating agent, correctives, lubricant and fluidizer.The weight portion proportion of composing of above-mentioned said each component is:
Adefovir ester 10
Solid dispersion carrier 4-12
Filler 80-140
Disintegrating agent 5-15
Correctives is an amount of
Lubricant 0.5-3.5
Fluidizer 0-5 wherein, the solid dispersion carrier selects polyvinylpyrrolidone (PVP), at least a in the Polyethylene Glycol (as PEG6000, PEG4000 etc.); Filler is selected from least a in microcrystalline Cellulose (MCC) or the lactose; It is that mol ratio that hydroxypropyl replaces is at least a in low-substituted hydroxypropyl cellulose (L-HPC), crospolyvinylpyrrolidone (PPVP) or cross-linking sodium carboxymethyl cellulose of 4%-10% and composition thereof that disintegrating agent is selected from carboxymethyl starch sodium (CMC-Na), cellulose hydroxyl; Lubricant is selected from least a in magnesium stearate, sodium lauryl sulphate or the Pulvis Talci; Fluidizer is selected from least a in micropowder silica gel or the hydrated sodium aluminosilicate.
In above-mentioned pharmaceutical preparation, the preferred use amount of said solid dispersion carrier is the 8-10 weight portion, outside using divided by the single form composition, can also adopt by polyvinylpyrrolidone/Polyethylene Glycol form of mixtures that (as the compound mode of the desirable equal proportion amount of most convenient) formed by weight 5～7/7～5.The preferred use amount of said filler is the 100-120 weight portion in the above-mentioned composition; The preferred use amount of disintegrating agent is the 8-12 weight portion.These components except that can single mode using, compound mode that can as required equally also can be suitable is used, rule of thumb, when adopting compound mode to use, the general composition that uses simultaneously is advisable to be no more than 2～3 kinds.Test shows, advantage when adopt mixing the solid dispersion of composition form and/or disintegrating agent helps to reduce total consumption of this constituents, can also improve the particulate compressibility of tabletting, become making in the hardness raising of tablet, can also not influence the time limit of disintegrate.
Said correctives can commonly usedly in present medicine have in the natural or artificial sweetening agent or fruit essence of flavored action in the above-mentioned oral disintegration tablets medicine preparation, as selecting wherein one or more in the correctives compositions commonly used such as aspartame, mannitol, stevioside, sorbitol, Mentholum.The effect of correctives is the disagreeable taste of masking agents, be beneficial to swallow, so its use amount ratio can operate in the usual way, for example, generally all can in 5-25 weight portion scope.
In above-mentioned composition form, especially recommend to make it can also have the effect that promotes the principal agent stripping simultaneously the use that cooperatively interacts of sodium lauryl sulphate and solid dispersion carrier.
The above-mentioned adefovir dipivoxil oral disintegration tablets medicine preparation of the present invention can pass through the wet granule compression tablet method, or mode such as direct compression process prepares.
The process of wet granule compression tablet method is: active drug composition adefovir ester and pharmacy can be accepted filler and the abundant mix homogeneously of correctives in the auxiliary element and pulverized 100 mesh sieves (particle diameter≤0.14 millimeter), with made weight ratio by the solid dispersion carrier in the auxiliary element is after the aqueous solution of 10-25% is made wet granular, (disintegrating agent can add simultaneously and mix before system in 40 ℃ of-60 ℃ of vacuum dryings, or can be coated on particle surface jointly with lubricant in the dry back of granulating), dried granule and cross 40 mesh sieves (particle diameter≤0.38 millimeter) granulate after tabletting.Wherein the adding mode of said disintegrating agent preferably is adopted as and is coated on the mode of making particle surface after predrying (for example in the drying under 105 ℃ of conditions) and handles.
The process of direct compression method is: with active drug composition adefovir ester with the suitable common solvent of dissolubility, as methanol, ethanol, acetone, chloroform equal solvent, after wherein dissolve with ethanol is used in special recommendation, above-mentioned pharmacy adds after can accept correctives in the auxiliary element and filler and absorb, eliminate solvent, add the abundant mix homogeneously direct compression of remaining auxiliary element again.The solvent load of said meltage wherein, the by weight/volume that generally can be adefovir ester/solvent is the scope of 1/1-4.
Result of the test shows that said medicine of the present invention can have suitable hardness, and promptly having in preparation and transportation not can disruptive enough hardness; The disintegrative result of the test of carrying out then shows simultaneously: according to the pharmacopeia prescriptive procedure, being shattered into interior disintegrate fully in 1 minute in 2ml water can be by the particulate (the pharmacopeia required standard was 30 mesh sieves) of 40 mesh sieves.Therefore as the said medicine of the present invention of gastrointestinal administration approach, its disintegration rate and effect and all very good to sheltering of adverse drug taste, can solve old people, child satisfactorily and the patient of dysphagia is arranged, and going out or lacking medication patient's in particular cases such as drinking water condition the problem of taking medicine, when taking medicine is contained in need not auxiliary drinking-water in the mouth can fully disintegrate in the oral cavity in 60 seconds.
Said medicine preparation of the present invention can directly use conventional tablet pharmaceutical equipment to produce and use the pressing process preparation, need not overlapping investment, and preparation technology is simple and convenient, has the excellent popularization prospect.
The specific embodiment by the following examples is described in further detail foregoing of the present invention again.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.Do not breaking away under the above-mentioned technological thought situation of the present invention, various replacements or change according to ordinary skill knowledge and customary means are made all should comprise within the scope of the invention.
The specific embodiment
Embodiment 1
Medicine is formed: adefovir ester 10g
Microcrystalline Cellulose 100g
Polyethylene Glycol-6000 8g
Sodium lauryl sulphate 2g
Stevioside 0.75g
Mentholum 0.75g
Low-substituted hydroxypropyl cellulose (L-HPC) 6g
Sorbitol instant 8g
Strawberry essence 0.5g
Pulvis Talci 1g
Magnesium stearate 0.3g
Be made for: 1000
Preparation method: prepare with wet granulation technology: sorbitol instant, microcrystalline Cellulose and adefovir ester blend are merged porphyrize cross 100 mesh sieves with conventional tablet equipment, Polyethylene Glycol, sodium lauryl sulphate, stevioside, Mentholum are made the 30ml aqueous solution, add above-mentioned mixing fine powders, make soft material, vacuum drying below 60 ℃, moisture Control is 2.5%.Sieve is got fine powder and is added strawberry essence in right amount, adds the pre-dried low-substituted hydroxypropyl cellulose of recipe quantity and magnesium stearate, Pulvis Talci more respectively, crosses 40 mesh sieve granulate mixings, carries out granule content and detects.Determine the heavy back of sheet tabletting, promptly get oral cavity disintegration tablet.
External slaking test: remove ionized water 1ml, add 1 of preproduction, repeat all disintegrates in 60 seconds 6 times.
Embodiment 2
Medicine is formed: adefovir ester 10g
Polyvinylpyrrolidone 4g
Stevioside 1g
Mentholum 0.75g
Strawberry essence 0.5g
Microcrystalline Cellulose 110g
Carboxymethyl starch sodium 6g
Mannitol 20g
Micropowder silica gel 5g
Magnesium stearate 0.75g
Be made for: 1000
Preparation method: direct compression technology mode preparation in the conventional tablet pharmaceutical equipment: with adefovir ester, stevioside, Mentholum, strawberry essence with dissolve with ethanol or after being aided with ultrasonic Treatment and promoting dissolving, absorb with mannitol, microcrystalline Cellulose, mix thoroughly, under the condition of vacuum-0.096Mpa and≤50 ℃, wave most ethanol, drying.Carboxymethyl starch sodium is crossed 80 mesh sieves, and dry under preference temperature, moisture Control adds in the above-mentioned material with magnesium stearate, micropowder silica gel in the lump below 1%, and the mixing that sieves carries out mixture content and detects.Determine the heavy back of sheet tabletting, promptly get oral cavity disintegration tablet.
External slaking test: remove ionized water 1ml, add 1 of preproduction, repeat all disintegrates in 60 seconds 6 times.
Embodiment 3
Medicine is formed: adefovir ester 10g
Microcrystalline Cellulose 80g
Lactose 35g
Low-substituted hydroxypropyl cellulose 6g
Polyvinylpyrrolidone 4g
Stevioside 0.75g
Mentholum 0.75g
Strawberry essence 0.5g
Sorbitol 5g
Micropowder silica gel 5g
Magnesium stearate 0.75g
Be made for: 1000
Preparation method: in the conventional tablet pharmaceutical equipment, prepare: lactose, microcrystalline Cellulose and adefovir ester mixing porphyrize are crossed 100 mesh sieves with the wet method tablet forming technique.Polyvinylpyrrolidone, stevioside, Mentholum, strawberry essence are made the 30ml aqueous solution, add above-mentioned mixing fine powders, make wet granular, in vacuum drying below 60 ℃, moisture is no more than 2.5%, add again recipe quantity through the pre-dried low-substituted hydroxypropyl cellulose of preference temperature (moisture≤1%) and magnesium stearate, micropowder silica gel, cross 40 mesh sieve mixings, carry out granule content and detect, determine the heavy back of sheet tabletting, promptly get oral cavity disintegration tablet.
External slaking test: remove ionized water 1ml, add 1 of preproduction, repeat all disintegrates in 60 seconds 6 times.
Embodiment 4
Medicine is formed: adefovir ester 10g
Microcrystalline Cellulose 100g
Polyethylene Glycol-6000 3g
Polyvinylpyrrolidone 3g
Sodium lauryl sulphate 2g
Stevioside 0.75g
Mentholum 0.75g
Low-substituted hydroxypropyl cellulose (L-HPC) 3g
Carboxymethyl starch sodium 3g
Sorbitol instant 8g
Strawberry essence 0.5g
Pulvis Talci 1g
Magnesium stearate 0.3g
Be made for: 1000
Preparation method and slaking test are all with embodiment 1.
Embodiment 5
Medicine is formed: adefovir ester 10g
Microcrystalline Cellulose 100g
Polyethylene Glycol-6000 3.5g
Polyvinylpyrrolidone 2.5g
Sodium lauryl sulphate 2g
Stevioside 0.75g
Mentholum 0.75g
Low-substituted hydroxypropyl cellulose (L-HPC) 2.5g
Carboxymethyl starch sodium 2.5g
Mannitol 8g
Strawberry essence 0.5g
Pulvis Talci 1g
Magnesium stearate 0.3g
Be made for: 1000
Preparation method and slaking test are all with embodiment 2.
In the above embodiments 4 and 5, what solid dispersion carrier and disintegrating agent all adopted mixes the form of forming by two kinds of heterogeneities, its remarkable advantage is to improve particulate compressibility, becomes making in the hardness raising of tablet, does not influence the disintegration of tablet.
Claims (10)
1. adefovir dipivoxil oral disintegration tablets medicine preparation, with the adefovir ester is the active drug composition, form jointly with the acceptable auxiliary element of pharmacy, it is characterized in that said auxiliary element is mainly solid dispersion carrier, filler, disintegrating agent, correctives, lubricant and fluidizer, the weight portion proportion of composing of said each component is:
Adefovir ester 10
Solid dispersion carrier 4-12
Filler 80-140
Disintegrating agent 5-15
Correctives is an amount of
Lubricant 0.5-3.5
Fluidizer 0-5
Wherein, the solid dispersion carrier is selected from least a in polyvinylpyrrolidone, the Polyethylene Glycol; Filler is selected from least a in microcrystalline Cellulose or the lactose; It is that mol ratio that hydroxypropyl replaces is at least a in the low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone of 4%-10% that disintegrating agent is selected from cross-linking sodium carboxymethyl cellulose and composition thereof, carboxymethyl starch sodium, hydroxyl; Lubricant is selected from least a in magnesium stearate, sodium lauryl sulphate or the Pulvis Talci; Fluidizer is selected from least a in micropowder silica gel or the hydrated sodium aluminosilicate.
2. adefovir dipivoxil oral disintegration tablets medicine preparation as claimed in claim 1, the preferred use amount that it is characterized in that said solid dispersion carrier is the 8-10 weight portion.
3. adefovir dipivoxil oral disintegration tablets medicine preparation as claimed in claim 1 or 2 is characterized in that said solid dispersion carrier is by weight 5～7/7～5 mixture of forming by polyvinylpyrrolidone/Polyethylene Glycol.
4. adefovir dipivoxil oral disintegration tablets medicine preparation as claimed in claim 1, the preferred use amount that it is characterized in that said filler is the 100-120 weight portion.
5. adefovir dipivoxil oral disintegration tablets medicine preparation as claimed in claim 1, the preferred use amount that it is characterized in that said disintegrating agent is the 6-9 weight portion.
6. as claim 1 or 5 described adefovir dipivoxil oral disintegration tablets medicine preparations, it is characterized in that the form of mixtures of said disintegrating agent for forming by two kinds of heterogeneities.
7. adefovir dipivoxil oral disintegration tablets medicine preparation as claimed in claim 1 is characterized in that solid dispersion carrier and the sodium lauryl sulphate in the said auxiliary element united use.
8. the preparation method of adefovir dipivoxil oral disintegration tablets medicine preparation, it is characterized in that adefovir ester and pharmacy can be accepted filler and the abundant mix homogeneously of correctives in the auxiliary element and be crushed to particle diameter≤0.14 millimeter, with make the aqueous solution granulation that weight ratio is 10-25% by the solid dispersion carrier in the auxiliary element after, in 40 ℃ of-60 ℃ of vacuum dryings, disintegrating agent can add before granulating and mix or be coated on particle surface jointly in granulate back and lubricant, makes tabletting behind particle diameter≤0.38 mm granules.
9. the preparation method of adefovir dipivoxil oral disintegration tablets medicine preparation as claimed in claim 8 is characterized in that preferred employing is coated on the mode of making particle surface with pre-dried disintegrating agent and handles.
10. the preparation method of adefovir dipivoxil oral disintegration tablets medicine preparation, it is characterized in that active drug composition adefovir ester is dissolved with the dissolubility appropriate solvent, can accept to eliminate solvent after correctives in the auxiliary element and filler absorb with pharmacy, add the abundant mix homogeneously direct compression of remaining auxiliary element again.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510021349A CN1903208B (en) | 2005-07-28 | 2005-07-28 | Adefovir dipivoxil oral disintegration tablets preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510021349A CN1903208B (en) | 2005-07-28 | 2005-07-28 | Adefovir dipivoxil oral disintegration tablets preparation method |
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| CN1903208A true CN1903208A (en) | 2007-01-31 |
| CN1903208B CN1903208B (en) | 2010-05-05 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN200510021349A Expired - Fee Related CN1903208B (en) | 2005-07-28 | 2005-07-28 | Adefovir dipivoxil oral disintegration tablets preparation method |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010032958A3 (en) * | 2008-09-17 | 2010-06-24 | 씨제이제일제당 (주) | Stabilized solid dispersion of adefovir dipivoxil and preparation method thereof |
| CN101284011B (en) * | 2007-04-09 | 2010-08-18 | 杭州民生药业有限公司 | Oleanolic acid orally disintegrating tablet and preparation method thereof |
| CN102293776A (en) * | 2010-06-22 | 2011-12-28 | 天津药物研究院药业有限责任公司 | Adefovir dipivoxil solid preparation and its preparation method |
| CN105534933A (en) * | 2016-01-19 | 2016-05-04 | 美吉斯制药（厦门）有限公司 | Vortioxetine orally disintegrating tablet and preparation method thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013029198A1 (en) * | 2011-08-29 | 2013-03-07 | 天津泰普药品科技发展有限公司 | Adefovir dipivoxil solid formulation and preparation method therefor |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1546046A (en) * | 2003-12-08 | 2004-11-17 | 杨喜鸿 | Adefovir dipivoxil dispersing tablet and its preparation |
-
2005
- 2005-07-28 CN CN200510021349A patent/CN1903208B/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284011B (en) * | 2007-04-09 | 2010-08-18 | 杭州民生药业有限公司 | Oleanolic acid orally disintegrating tablet and preparation method thereof |
| WO2010032958A3 (en) * | 2008-09-17 | 2010-06-24 | 씨제이제일제당 (주) | Stabilized solid dispersion of adefovir dipivoxil and preparation method thereof |
| CN102149715A (en) * | 2008-09-17 | 2011-08-10 | Cj第一制糖株式会社 | Stabilized solid dispersion of adefovir dipivoxil and preparation method thereof |
| JP2012502902A (en) * | 2008-09-17 | 2012-02-02 | シージェイ チェルジェダン コーポレイション | Stabilized solid dispersion of adefovir dipivoxil and process for producing the same |
| CN102293776A (en) * | 2010-06-22 | 2011-12-28 | 天津药物研究院药业有限责任公司 | Adefovir dipivoxil solid preparation and its preparation method |
| CN105534933A (en) * | 2016-01-19 | 2016-05-04 | 美吉斯制药（厦门）有限公司 | Vortioxetine orally disintegrating tablet and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN1903208B (en) | 2010-05-05 |
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Owner name: CHONGQING SHENGHUAXI PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: SHENHUAXI PHARMACEUTICAL CO., LTD., CHONGQING |
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Address after: 400063 Chongqing Nan'an District Tu Shan Zhen Ren Jia Wan Huang Po Patentee after: Chongqing Shenghuaxi Pharmaceutical Co., Ltd. Address before: 400063 Chongqing Nan'an District Tu Shan Zhen Ren Jia Wan Huang Po Patentee before: Shenhuaxi Pharmaceutical Co., Ltd., Chongqing |
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Granted publication date: 20100505 Termination date: 20180728 |