CN103284973A - Adefovir dipivoxil composition and preparation method thereof - Google Patents
Adefovir dipivoxil composition and preparation method thereof Download PDFInfo
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Abstract
The invention discloses an adefovir dipivoxil composition and a preparation method thereof. The adefovir dipivoxil composition is prepared from the following components in percentage by weight: 5-15% of adefovir dipivoxil, 20-80% of filler, 4-15% of a disintegrating agent, 0-5% of a surfactant, 0-5% of a lubricant, and 1-10% of a coating material. The preparation method is implemented through carrying out direct tabletting or dry granulation and tabletting on raw materials and supplementary materials. The adefovir dipivoxil composition prepared by using the method disclosed by the invention is reliable in quality, stable in properties, simple in production process and low in cost, and satisfies the requirements of preparation mass-production.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to adefovir ester tablet and preparation method thereof.
Background technology
Adefovir ester is a kind of new anti-hepatitis B virus (HBV) medicine, also is the another kind of oral anti-HBV medicine behind lamivudine.This medicine is the purine analog derivative, but competitive inhibition HBV polymerase, and the prolongation of termination HBV DNA chain, be novel open chain ucleotides broad-spectrum antiviral medicament.This medicine is gone on the market in the U.S. by FDA (FDA) approval in JIUYUE, 2002, and Chinese II, the clinical registration test of III phase also start in December, 2002.Be applicable to that drug resistance person has been taken place for long-term prescription and lamivudine.Adefovir ester is comparatively slow to the onset time of HBV, but it is low that chemical sproof probability takes place, and the drug effect reserve strength is strong, and also effective to producing virus variation person, is present to the best alternative medicine of drug resistance case treatment is arranged, and has solved the chemical sproof difficult problem of HBV.
Anti-hepatic-B virus medicine on the world market mainly comprises two big classes, interferons and nucleoside or nucleoside analog at present.The latter mainly contains four kinds of lamivudine, adefovir ester, Entecavir and Sebivos.
Lamivudine 1998 listing monopolizes the market as long as five years.Now higher because of its drug resistance incidence rate, 5 years resistant rate are up to 70%, and the market share is atrophy gradually.The adefovir ester antivirus action is clear and definite, and prolonged application is safe, and the drug resistance incidence rate is low and time of occurrence is late, by internationally recognized be the first-line treatment medication of various chronic viral hepatitis Bs, and as lamivudine resistance patient's first-selection.The existing market share constantly promotes, and presents a rapidly rising trend, and has broad application prospects.
Adefovir ester is the prodrug of adefovirdipivoxil, phosphate-based electronegative because of adefovirdipivoxil, absorb in the oral hindgut badly, adefovir ester then can improve bioavailability, is discharged free adefovirdipivoxil performance antivirus action by esterase hydrolyzed rapidly after oral.
Adefovir ester tablet and the capsule of listing mainly are with the wet granulation medicine at present, and this method of granulating need add the binding agent of liquid supplementary material is made soft material, and the back obtains finished product by dry, tabletting.But in preparation process, because humidity is too big, cause the hydrolysis of part adefovir ester, increased the generation quantity of adefovir (AD) monoester, caused the adefovir dipivoxil crystal form variation, reduced medicine stability.
Summary of the invention
The objective of the invention is to overcome the deficiency that wet granulation causes adefovir ester tablet stability difference, provide two kinds of new preparation technologies with the good adefovir ester tablet of obtained performance.New technology can reduce the generation quantity of adefovir (AD) monoester in the preparation process effectively, and does not cause the variation of adefovir dipivoxil crystal form, and stripping curve is better, process stabilizing, and production process can be effectively controlled.
This tablet stability is strong, the bioavailability height, and technology is simple, and operation is fit to large-scale production less.
A Fudewei ester tablet ingredients of the present invention comprises adefovir ester and adjuvant, and its percentage by weight is adefovir ester: 5-25%; Adjuvant: 65-90%; Coating component: 1-10%.
A Fudewei ester additive of tablet of the present invention can be filler (diluent), disintegrating agent, surfactant, lubricant,
In the binding agent one or more.
A Fudewei ester tablet of the present invention is made by following percentage by weight by following component:
The present invention mainly adopts in lactose, microcrystalline Cellulose, Ludipress LCE, SMCC, sucrose, starch, sorbitol, mannitol, Icing Sugar, dextrin, the pre-paying starch one or more to control the release of medicine as filler (diluent), by screening different proportion filler to reach ideal effect.
The present invention by in screening low-substituted hydroxypropyl cellulose, starch, Sodium Hydroxymethyl Stalcs, sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, the cross-linking sodium carboxymethyl cellulose one or more as disintegrating agent to reach release preferably.
The present invention selects for use in stearic acid, micropowder silica gel, Pulvis Talci, magnesium stearate, the Macrogol 4000 one or more as lubricant.
The present invention selects for use in sodium lauryl sulphate, tween, the span one or more to improve the tablet release as surfactant.
A Fudewei ester tablet coating weight percentages of components of the present invention is: coating material: 2-15%; Coating solvent: 85-98%.Select for use in hypromellose, hydroxypropyl cellulose, polyvinylpyrrolidone, the Opadry one or more as coating material; Select for use in water, the ethanol one or more as the coating solvent.
The present invention selects for use compressing dry granulation and two kinds of preparation technologies of direct powder compression to make A Fudewei ester tablet.
The direct powder compression of the A Fudewei ester tablet that the present invention is related comprises the steps:
(1) adefovir ester is crushed to mean diameter＜50 μ m with super micron mill, adjuvant is crossed the 60-120 mesh sieve respectively, and is standby;
(2) take by weighing recipe quantity adefovir ester and disintegrating agent and add in the wet-mixed granulation machine, set mixing speed 450r/min, chopping speed 1200r/min mixes 180s, adds recipe quantity filler mixing 300s after the discharging, adds recipe quantity mix lubricant 50s again;
(3) get step 2 mixture determining powder fluidity (θ represents with angle of repose), moisture and drug content, can satisfy during θ≤40 ° and produce mobile needs, drug content is controlled between 7.0%～9.0%, and moisture is controlled below 0.2%;
(4) step 2 mixture is added in the tablet machine, namely get label with the shallow arc punch die of diameter 7.0mm tabletting, the control principal pressure is 6000N, and the tablet machine rotating speed is 30r/min, and every contains adefovir ester 10mg;
(5) the Opadry coating powder is at the uniform velocity added in 95% ethanol of stirring, and continue to stir 45min and disperse fully to coating materials, be made into concentration and be 8% coating solution, standby;
(6) preheating coating pan adds qualified label metering back in the coating pan, and the adjusting rotating speed is 3-5r/min, and the preheating label is adjusted spray gun position, atomizing pressure, flow and turnover pathogenic wind-warm degree.When label is preheating to 40-45 ℃, begin spraying, control hot blast temperature and suitable spray speed make the sheet bed remain on 39-43 ℃, keep the unilateral enough liquid measures and in time dry that have.Spray process suitably improves rotating speed to 10-15r/min, and the total coated time is about 3h, gets the adefovir ester coated tablet.
The compressing dry granulation of the present invention's A Fudewei ester tablet comprises the steps:
(1) adefovir ester is crushed to mean diameter＜50 μ m with super micron mill, filler, surfactant, disintegrating agent were pulverized 100 mesh sieves, and be standby;
(2) take by weighing recipe quantity adefovir ester and part disintegrating agent and add in the wet-mixed granulation machine, set mixing speed 450r/min, chopping speed 1200r/min mixes 180s, adds recipe quantity filler, surfactant mixing 300s after the discharging;
(3) step 2 mixture is joined in the dry granulation machine, regulator solution pinch roller pressure is 1.5-2.0MPa, and rotating speed is that 9-12r/min is pressed into the thick thin strip dry tablet of 2mm, crosses 20 mesh sieve granulate after pulverizer is ground into granule, makes dried granule;
(4) in the dried granule of step 3, add surplus disintegrating agent and recipe quantity lubricant, mix 3min until evenly;
(5) get step 4 mixture determining powder fluidity (θ represents with angle of repose), moisture and drug content, can satisfy during θ≤40 ° and produce mobile needs, drug content is controlled between 7.0%～9.0%, and moisture is controlled below 0.2%;
(6) step 4 mixture is added in the tablet machine, namely get label with the shallow arc punch die of diameter 7.0mm tabletting, the control principal pressure is 6000N, and the tablet machine rotating speed is 30r/min, and every contains adefovir ester 10mg;
(7) the Opadry coating powder is at the uniform velocity added in 95% ethanol of stirring, and continue to stir 45min and disperse fully to coating materials, be made into concentration and be 8% coating solution, standby;
(8) preheating coating pan adds qualified label metering back in the coating pan, and the adjusting rotating speed is 3-5r/min, and the preheating label is adjusted spray gun position, atomizing pressure, flow and turnover pathogenic wind-warm degree.When label is preheating to 40-45 ℃, begin spraying, control hot blast temperature and suitable spray speed make the sheet bed remain on 39-43 ℃, keep the unilateral enough liquid measures and in time dry that have.Spray process suitably improves rotating speed to 10-15r/min, and the total coated time is about 3h, gets the adefovir ester coated tablet.
The present invention requires to detect outward appearance fineness and the color and luster uniformity of final drug in the medicament preparation process; Detect hardness and the wearability of final drug; Detect dissolution, release, uniformity of dosage units, the microbial limit of final drug; Detect the weight differential degree between the finished product medicinal tablet.
The used low-substituted hydroxypropyl cellulose of the present invention is regulated the tablet disintegration rate as disintegrating agent.Use these two kinds of technologies of mixed-powder direct compression and dry granulation tabletting simultaneously.Adefovir ester sheet of the present invention has following characteristics:
1, rapid-action, disintegrate is rapid, and the dissolution test shows that the adefovir ester that has more than 95% is leachable, is conducive to body and absorbs, and bioavailability and blood drug level increase to some extent, can improve the effect of anti-hepatitis B.
2, avoid using wet granule compression tablet technology, reduced the generation quantity of adefovir (AD) monoester, can not cause that also adefovir dipivoxil crystal form changes, and has improved stability of drug.
3, add solubilizing agent and surfactant in the present invention's prescription, promoted adefovir ester release in vivo, be beneficial to the drug effect performance.
Description of drawings:
Fig. 1. the mixed-powder direct compression process prepares adefovir ester tablet process chart.
The specific embodiment
Exemplifying embodiment 1
Per 1000 tablets of adefovir ester tablets take by weighing material by following prescription:
The label prescription:
Coating fluid prescription:
Preparation process:
1, adefovir ester is crushed to mean diameter＜50 μ m with super micron mill, Ludipress LCE, carboxymethyl starch sodium are crossed 60 mesh sieves respectively, and be standby;
2, taking by weighing recipe quantity adefovir ester and carboxymethyl starch sodium adds in the wet-mixed granulation machine, set mixing speed 450r/min, chopping speed 1200r/min mixes 180s, add recipe quantity Ludipress LCE mixing 300s after the discharging, add the recipe quantity magnesium stearate again and mix 50s;
3, get step 2 mixture determining powder fluidity (θ represents with angle of repose), moisture and drug content, can satisfy during θ≤40 ° and produce mobile needs, drug content is controlled between 7.0%～9.0%, and moisture is controlled below 0.2%;
4, step 2 mixture is added in the tablet machine, namely get label with the shallow arc punch die of diameter 7.0mm tabletting, the control principal pressure is 6000N, and the tablet machine rotating speed is 30r/min, and every contains adefovir ester 10mg;
5, the Opadry coating powder is at the uniform velocity added in 95% ethanol of stirring, and continue to stir 45min and disperse fully to coating materials, be made into concentration and be 8% coating solution, standby;
6, preheating coating pan adds qualified label metering back in the coating pan, and the adjusting rotating speed is 3-5r/min, and the preheating label is adjusted spray gun position, atomizing pressure, flow and turnover pathogenic wind-warm degree.When label is preheating to 40-45 ℃, begin spraying, control hot blast temperature and suitable spray speed make the sheet bed remain on 39-43 ℃, keep the unilateral enough liquid measures and in time dry that have.Spray process suitably improves rotating speed to 10-15r/min, and the total coated time is about 3h, and the coating weightening finish is 3%.
Exemplifying embodiment 2
Per 1000 tablets of adefovir ester tablets take by weighing material by following prescription:
The label prescription:
Coating fluid prescription:
Preparation process:
1, adefovir ester is crushed to mean diameter＜50 μ m with super micron mill, SMCC, crospolyvinylpyrrolidone are crossed 60 mesh sieves respectively, and be standby;
2, taking by weighing recipe quantity adefovir ester and crospolyvinylpyrrolidone adds in the wet-mixed granulation machine, set mixing speed 450r/min, chopping speed 1200r/min mixes 180s, add recipe quantity SMCC mixing 300s after the discharging, add the recipe quantity magnesium stearate again and mix 50s;
3, get step 2 mixture determining powder fluidity (θ represents with angle of repose), moisture and drug content, can satisfy during θ≤40 ° and produce mobile needs, drug content is controlled between 7.0%～9.0%, and moisture is controlled below 0.2%;
4, step 2 mixture is added in the tablet machine, namely get label with the shallow arc punch die of diameter 7.0mm tabletting, the control principal pressure is 6000N, and the tablet machine rotating speed is 30r/min, and every contains adefovir ester 10mg;
5, the Opadry coating powder is at the uniform velocity added in 95% ethanol of stirring, and continue to stir 45min and disperse fully to coating materials, be made into concentration and be 8% coating solution, standby;
6, preheating coating pan adds qualified label metering back in the coating pan, and the adjusting rotating speed is 3-5r/min, and the preheating label is adjusted spray gun position, atomizing pressure, flow and turnover pathogenic wind-warm degree.When label is preheating to 40-45 ℃, begin spraying, control hot blast temperature and suitable spray speed make the sheet bed remain on 39-43 ℃, keep the unilateral enough liquid measures and in time dry that have.Spray process suitably improves rotating speed to 10-15r/min, and the total coated time is about 3h, and the coating weightening finish is 3%.
Exemplifying embodiment 3
Per 1000 tablets of adefovir ester tablets take by weighing material by following prescription:
The label prescription:
Coating fluid prescription:
Preparation process:
1, adefovir ester is crushed to mean diameter＜50 μ m with super micron mill, pregelatinized Starch, tween, Macrogol 4000, microcrystalline Cellulose, carboxymethyl starch sodium were pulverized 100 mesh sieves, and be standby;
2, taking by weighing recipe quantity adefovir ester and part of sodium carboxymethyl starch adds in the wet-mixed granulation machine, set mixing speed 450r/min, chopping speed 1200r/min mixes 180s, adds recipe quantity pregelatinized Starch, tween, Macrogol 4000, microcrystalline Cellulose mixing 300s after the discharging;
3, step 2 mixture is joined in the dry granulation machine, regulator solution pinch roller pressure is 1.5-2.0MPa, and rotating speed is that 9-12r/min is pressed into the thick thin strip dry tablet of 2mm, crosses 20 mesh sieve granulate after pulverizer is ground into granule, makes dried granule;
4, in the dried granule of step 3, add surplus carboxymethyl starch sodium and recipe quantity magnesium stearate, mix 3min until evenly;
5, get step 4 mixture determining powder fluidity (θ represents with angle of repose), moisture and drug content, can satisfy during θ≤40 ° and produce mobile needs, drug content is controlled between 7.0%～9.0%, and moisture is controlled below 0.2%;
6, step 4 mixture is added in the tablet machine, namely get label with the shallow arc punch die of diameter 7.0mm tabletting, the control principal pressure is 6000N, and the tablet machine rotating speed is 30r/min, and every contains adefovir ester 10mg;
7, the Opadry coating powder is at the uniform velocity added in 95% ethanol of stirring, and continue to stir 45min and disperse fully to coating materials, be made into concentration and be 8% coating solution, standby;
8, preheating coating pan adds qualified label metering back in the coating pan, and the adjusting rotating speed is 3-5r/min, and the preheating label is adjusted spray gun position, atomizing pressure, flow and turnover pathogenic wind-warm degree.When label is preheating to 40-45 ℃, begin spraying, control hot blast temperature and suitable spray speed make the sheet bed remain on 39-43 ℃, keep the unilateral enough liquid measures and in time dry that have.Spray process suitably improves rotating speed to 10-15r/min, and the total coated time is about 3h, and the coating weightening finish is 3%.
Exemplifying embodiment 4
Per 1000 tablets of adefovir ester tablets take by weighing material by following prescription:
The label prescription:
Coating fluid prescription:
Preparation process:
1, adefovir ester is crushed to mean diameter＜50 μ m with super micron mill, calcium lactate, microcrystalline Cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose were pulverized 100 mesh sieves, and be standby;
2, take by weighing recipe quantity adefovir ester and low-substituted hydroxypropyl cellulose and add in the wet-mixed granulation machine, set mixing speed 450r/min, chopping speed 1200r/min mixes 180s, adds recipe quantity calcium lactate, microcrystalline Cellulose mixing 300s after the discharging;
3, step 2 mixture is joined in the dry granulation machine, regulator solution pinch roller pressure is 1.5-2.0MPa, and rotating speed is that 9-12r/min is pressed into the thick thin strip dry tablet of 2mm, crosses 20 mesh sieve granulate after pulverizer is ground into granule, makes dried granule;
4, in the dried granule of step 3, add carboxymethyl starch sodium and recipe quantity magnesium stearate, mix 3min until evenly;
5, get step 4 mixture determining powder fluidity (θ represents with angle of repose), moisture and drug content, can satisfy during θ≤40 ° and produce mobile needs, drug content is controlled between 7.0%～9.0%, and moisture is controlled below 0.2%;
6, step 4 mixture is added in the tablet machine, namely get label with the shallow arc punch die of diameter 7.0mm tabletting, the control principal pressure is 6000N, and the tablet machine rotating speed is 30r/min, and every contains adefovir ester 10mg;
7, the Opadry coating powder is at the uniform velocity added in 95% ethanol of stirring, and continue to stir 45min and disperse fully to coating materials, be made into concentration and be 8% coating solution, standby;
8, preheating coating pan adds qualified label metering back in the coating pan, and the adjusting rotating speed is 3-5r/min, and the preheating label is adjusted spray gun position, atomizing pressure, flow and turnover pathogenic wind-warm degree.When label is preheating to 40-45 ℃, begin spraying, control hot blast temperature and suitable spray speed make the sheet bed remain on 39-43 ℃, keep the unilateral enough liquid measures and in time dry that have.Spray process suitably improves rotating speed to 10-15r/min, and the total coated time is about 3h, and the coating weightening finish is 3%.
Experimental example 5 quality determinations
The adefovir ester sheet that exemplifying embodiment 1-4 is made carries out quality examination with reference to two appendix of Chinese Pharmacopoeia version in 2010.Inspection item comprises appearance character, hardness, friability, disintegration, dissolution, related substance, content.Above item inspection all meets the every regulation of tablet.
The result is as shown in table 1.
Table 1 adefovir ester tablet quality check result
The result shows that the every inspection of self-control adefovir ester sheet meets the pharmacopeia regulation, satisfies prescription.
Experimental example 6 stability experiments
For preparation technology, packing and condition of storage for the adefovir ester sheet provide foundation, experiment that the present invention has carried out influence factor's experiment, acceleration is tested and room temperature keeps sample is the stability that index has been investigated the adefovir ester tablet with appearance character, dissolution, content, related substance.
The adefovir ester tablet that the invention process example 1-4 makes all has good stable, and this experiment is the stability data that example has been listed the adefovir ester sheet with exemplifying embodiment 1.
Influence factor's experimental technique:
Sample thief places respectively under 60 ℃ of the high temperature, 40 ℃, illumination 4000Lx scholar 500Lx, high humidity RH75%, RH92.5% condition, respectively at sampling in the 0th, 5,10 day, investigates the variation of its appearance character, dissolution, content, related substance.
The result is as shown in table 2.
Table 2 adefovir ester sheet influence factor experimental result
The result shows, adefovir ester sheet every index under strong illumination does not have significant change, its related substances surpasses 1.0% under 60 ℃ of conditions of high temperature, the moisture absorption weightening finish is all greater than 5% under super-humid conditions, for guaranteeing this product stability, should adopt medicinal high-density polyethylene plastics bottle, aluminum plastic film seals, in add silica-gel desiccant packing.
Accelerate the measuring method:
Take from adefovir ester tablet processed and under 40 ℃, the condition of RH75%, adopt simulation listing packaged form to be positioned in the hermetic container, respectively at sampling in the 0th, 1,2,3,6 month, investigate the variation of its appearance character, dissolution, content, related substance.
The result is as shown in table 3.
Table 3 adefovir ester sheet accelerates experimental result
The result shows that the adefovir ester sheet was placed six months under the acceleration experiment condition, appearance character, dissolution, content, related substance do not have significant change, and tablet does not have hygroscopic effect.As seen, self-control adefovir ester sheet is stable under six months acceleration environment.
The room temperature measuring method that keeps sample:
Take from adefovir ester tablet processed and under 25 ℃, the condition of RH60 ± 10%, placed 12 months, respectively at sampling in the 0th, 3,6,9,12 month, investigate the variation of its appearance character, dissolution, content, related substance.
The result is as shown in table 4.
The table 4 adefovir ester sheet room temperature experimental result that keeps sample
The result shows that the adefovir ester sheet was placed 12 months under room temperature keeps sample condition, appearance character, dissolution, content, related substance do not have significant change.As seen, self-control adefovir ester sheet is stable under 12 months room temperature keeps sample condition.
Conclusion, adefovir ester sheet provided by the invention have adopted potent disintegrating agent and have added the dissolving that proper amount of surfactant has promoted adefovir ester, have improved dissolution and its bioavailability of adefovir ester.Adopt art for coating, improved the stability of adefovir ester.Adefovir ester piece preparation method provided by the invention has simple, the stay-in-grade advantage of technology, satisfies the requirement of industrialized great production.
Above-mentioned exemplifying embodiment and experimental example are to further specifying that the present invention does, but do not limit the present invention.All any modifications of making in the present invention's spirit and principle, replacement etc. all are included in the protection domain of the present invention.
Claims (9)
1. an adefovir ester tablet is characterized in that comprising in its tablet adefovir ester and adjuvant, and its percentage by weight is adefovir ester: 5-25%; Adjuvant: 65-90%; Coating component: 1-10%.
2. adefovir ester tablet according to claim 1 is characterized in that described adjuvant can be one or more in filler (diluent), disintegrating agent, surfactant, lubricant, the binding agent.
3. according to claim 1,2 described adefovir ester tablets, it is characterized in that tablet made by following percentage by weight by following component:
。
4. according to claim 1,2,3 any described adefovir ester tablets, it is characterized in that described filler (diluent) can be one or more in Ludipress LCE, SMCC, lactose, microcrystalline Cellulose, sucrose, starch, sorbitol, mannitol, Icing Sugar, dextrin, the pre-paying starch; Described disintegrating agent can be one or more in low-substituted hydroxypropyl cellulose, starch, Sodium Hydroxymethyl Stalcs, sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, the cross-linking sodium carboxymethyl cellulose; Described lubricant can be one or more in stearic acid, micropowder silica gel, Pulvis Talci, magnesium stearate, the Macrogol 4000; Described surfactant can be one or more in sodium lauryl sulphate, tween, the span.
5. according to claim 1,2,3 any described adefovir ester tablets, it is characterized in that described coating component comprises that percentage by weight is: the coating material of 2-15%, 85-98% coating solvent.
6. adefovir ester tablet according to claim 5 is characterized in that described coating material can be one or more in hypromellose, hydroxypropyl cellulose, polyvinylpyrrolidone, the Opadry; Described coating solvent can be one or more in water, the ethanol.
7. a method for preparing as the described adefovir ester tablet of claim 1-6 is characterized in that described method is compressing dry granulation and direct powder compression.
8. a method for preparing as the described adefovir ester tablet of claim 1-6 is characterized in that, described method is direct powder compression, may further comprise the steps:
(1) adefovir ester is crushed to mean diameter＜50 μ m with super micron mill, adjuvant is crossed the 60-120 mesh sieve respectively, and is standby;
(2) take by weighing recipe quantity adefovir ester and disintegrating agent and add in the wet-mixed granulation machine, set mixing speed 450r/min, chopping speed 1200r/min mixes 180s, adds recipe quantity filler mixing 300s after the discharging, adds recipe quantity mix lubricant 50s again;
(3) get step 2 mixture determining powder fluidity (θ represents with angle of repose), moisture and drug content, can satisfy during θ≤40 ° and produce mobile needs, drug content is controlled between 7.0%～9.0%, and moisture is controlled below 0.2%;
(4) step 2 mixture is added in the tablet machine, namely get label with the shallow arc punch die of diameter 7.0mm tabletting, the control principal pressure is 6000N, and the tablet machine rotating speed is 30r/min, and every contains adefovir ester 10mg;
(5) the Opadry coating powder is at the uniform velocity added in 95% ethanol of stirring, and continue to stir 45min and disperse fully to coating materials, be made into concentration and be 8% coating solution, standby;
(6) preheating coating pan adds qualified label metering back in the coating pan, and the adjusting rotating speed is 3-5r/min, and the preheating label is adjusted spray gun position, atomizing pressure, flow and turnover pathogenic wind-warm degree.When label is preheating to 40-45 ℃, begin spraying, control hot blast temperature and suitable spray speed, make the sheet bed remain on 39-43 ℃, keep the unilateral enough liquid measures and in time dry that have, spray process suitably improves rotating speed to 10-15r/min, the total coated time is about 3h, coated tablet weightening finish 3%.
9. a method for preparing as the described adefovir ester tablet of claim 1-6 is characterized in that, described method is compressing dry granulation, may further comprise the steps:
(1) adefovir ester is crushed to mean diameter＜50 μ m with super micron mill, filler, surfactant, disintegrating agent are pulverized and crossed 100 mesh sieves respectively, and be standby;
(2) take by weighing recipe quantity adefovir ester and part disintegrating agent and add in the wet-mixed granulation machine, set mixing speed 450r/min, chopping speed 1200r/min mixes 180s, adds recipe quantity filler, surfactant mixing 300s after the discharging;
(3) step 2 mixture is joined in the dry granulation machine, regulator solution pinch roller pressure is 1.5-2.0MPa, and rotating speed is that 9-12r/min is pressed into the thick thin strip dry tablet of 2mm, crosses 20 mesh sieve granulate after pulverizer is ground into granule, makes dried granule;
(4) in the dried granule of step 3, add surplus disintegrating agent and recipe quantity lubricant, mix 3min until evenly;
(5) get step 4 mixture determining powder fluidity (θ represents with angle of repose), moisture and drug content, can satisfy during θ≤40 ° and produce mobile needs, drug content is controlled between 7.0%～9.0%, and moisture is controlled below 0.2%;
(6) step 4 mixture is added in the tablet machine, namely get label with the shallow arc punch die of diameter 7.0mm tabletting, the control principal pressure is 6000N, and the tablet machine rotating speed is 30r/min, and every contains adefovir ester 10mg;
(7) the Opadry coating powder is at the uniform velocity added in 95% ethanol of stirring, and continue to stir 45min and disperse fully to coating materials, be made into concentration and be 8% coating solution, standby;
(8) preheating coating pan adds qualified label metering back in the coating pan, and the adjusting rotating speed is 3-5r/min, the preheating label, adjust spray gun position, atomizing pressure, flow and turnover pathogenic wind-warm degree, when label is preheating to 40-45 ℃, begin spraying, control hot blast temperature and suitable spray speed, make the sheet bed remain on 39-43 ℃, keep the unilateral enough liquid measures and in time dry that have, spray process suitably improves rotating speed to 10-15r/min, the total coated time is about 3h, coated tablet weightening finish 3%.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104434850A (en) * | 2014-12-09 | 2015-03-25 | 李宝齐 | Oral solid medicine composition containing adefovir dipivoxil |
| CN114224858A (en) * | 2021-12-29 | 2022-03-25 | 辰欣药业股份有限公司 | Adefovir dipivoxil tablet and preparation method thereof |
Citations (3)
| 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 |
| CN101288674A (en) * | 2008-05-20 | 2008-10-22 | 福建广生堂药业有限公司 | New dosage medicinal application and using method of adefovir dipivoxil |
| CN103156820A (en) * | 2013-04-10 | 2013-06-19 | 悦康药业集团有限公司 | Adefovir dipivoxil tablets and preparation method thereof |
-
2013
- 2013-06-28 CN CN2013102649958A patent/CN103284973A/en active Pending
Patent Citations (3)
| 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 |
| CN101288674A (en) * | 2008-05-20 | 2008-10-22 | 福建广生堂药业有限公司 | New dosage medicinal application and using method of adefovir dipivoxil |
| CN103156820A (en) * | 2013-04-10 | 2013-06-19 | 悦康药业集团有限公司 | Adefovir dipivoxil tablets and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104434850A (en) * | 2014-12-09 | 2015-03-25 | 李宝齐 | Oral solid medicine composition containing adefovir dipivoxil |
| CN104434850B (en) * | 2014-12-09 | 2018-01-23 | 孙海英 | A kind of oral solid drug composition containing Aldoforwe ester |
| CN114224858A (en) * | 2021-12-29 | 2022-03-25 | 辰欣药业股份有限公司 | Adefovir dipivoxil tablet and preparation method thereof |
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