CN100435804C - Oral preparation of quick releasing stavudine, and producing method - Google Patents
Oral preparation of quick releasing stavudine, and producing method Download PDFInfo
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- CN100435804C CN100435804C CNB2005100116969A CN200510011696A CN100435804C CN 100435804 C CN100435804 C CN 100435804C CN B2005100116969 A CNB2005100116969 A CN B2005100116969A CN 200510011696 A CN200510011696 A CN 200510011696A CN 100435804 C CN100435804 C CN 100435804C
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Abstract
The present invention relates to an oral mouth cavity immediate release stavudine preparation with the advantages of rapid disintegration, immediate release and unhealthy taste mask for treating acquired immune deficiency syndrome, which can be prepared into orally disintegrating tablets, dispersive tablets and mouth solution tablets. The stavudine preparation is composed of the following raw materials by the weight percentage: 0.1 to 95% of stavudine and 5 to 99.9% of medicinal auxiliary materials. The oral immediate release stavudine preparation prepared by the present invention has the advantages of extended range of stavudine preparations, reasonable formula, good disintegrating property, no sandy sense or unpleasant taste in the mouth and simple and convenient preparation technology. By preparation devices for conventional medicinal tablets in the pharmaceutical industry, high-quality dispersive tablets, oral cavity instant tablets or orally disintegrating tablets can be economically and conveniently prepared on a large scale, the preparation has a high absorption rate and can enhance the biological availability and the blood medicine concentration of medicines so as to enhance the curative effect of resisting HIV virus, and the preparation has the advantages of convenient administration and good mouth feel and can be rapidly disintegrated in the mouth cavity when contacting sputum. Thus, the preparation provides convenience for a quantity of old people, children or patients who have difficulty in swallowing medicines and can not fetch water conveniently.
Description
Technical field:
The present invention relates to a kind of disintegrate rapidly for the treatment of acquired immune deficiency syndrome (AIDS), discharge and cover the stavudine oral cavity rapid release oral formulations and the preparation method of the bad sense of taste, comprise oral cavity disintegration tablet, dispersible tablet, mouthful molten.
Background technology:
Tablet is one of present most widely used oral dosage form, and it has takes and store and transport convenient and the stable advantage of medicine.But often, disintegrate and medicine stripping fully absorb because of slowly influencing medicine; Simultaneously, when dosage is big and need once take medicine more for a long time, often make troubles for the patient of old man, child and dysphagia.In this case, oral solution, suspensoid and Emulsion etc. are then comparatively superior, but liquid preparation has the relatively poor and shortcoming such as storing inconvenience etc. of medicine stability again.For this reason, the oral administration solid fast dissolving dosage form becomes the focus of new drug development in recent years.For in conjunction with the advantage of tablet and liquid preparation and avoid its shortcoming, over nearly 20 years, abroad developed meet water rapidly disintegrate form the dispersible tablet (dispersibletablets) of even suspension, oral cavity disintegration tablet, chewable tablet, Sublingual tablet etc. continue to bring out in addition.Wherein, dispersible tablet and oral cavity disintegration tablet because of its taking convenience, rapid-action, bioavailability is high, the good emphasis that becomes tablet exploitation of mouthfeel.
HIV (human immunodeficiency virus) (HIV) infects the acquired immunodeficiency syndrome (AIDS) that causes and is commonly called as acquired immune deficiency syndrome (AIDS), just worldwide is widely current at present, becomes great public health and social problem highly visible.
Domestic HIV (human immunodeficiency virus) infection number rises year by year, and at present number every year of China's aids infection, as not taking active and effective control, by 2010, China's patients infected hiv will be above 1,000 ten thousand people with 30% speed increase.At present, the medicine of world's listing treatment HIV virus has twenties kinds, domestic imitation patent expired and not at five or six kinds of essential drugses of the row of administrative protection, filled up the blank of state's internal therapy AIDS-treating medicine.But the simple and not high therapeutic effect that greatly reduces medicine of drug quality of listing dosage form.HAART inventor He Dayi professor also pays close attention to this problem representation when referring to domestic anti-AIDS drug, think domestic present AIDS-treating medicine on the quality of the pharmaceutical preparations not even as some countries of Africa.
Antiviral drugs, especially anti-AIDS drug dosage is generally bigger, and need take for a long time, and the general formulation that has gone on the market at present can't satisfy the needs in market, for example; With regard to the tablet and capsule that are commonly used for oral formulations, old man that many swallows are more weak and child just are unwilling to take these solid preparations, and the complaint medicine is difficult to swallow or esophagus stops up.With regard to powder and granule, they also easily are detained in the oral cavity, thereby produce unhappy sensation in mouth, also need drink water when taking above-mentioned preparation simultaneously, bring inconvenience.Therefore, the oral cavity rapid release dosage form of exploitation antiviral drugs can satisfy old man on the market, child and other swallows the patient's who takes inconvenience medication demand.
Summary of the invention:
The purpose of this invention is to provide a kind of disintegrate rapidly, discharge and cover the oral quick release dosage form of the stavudine of disagreeable taste, comprise dispersible tablet, oral cavity disintegration tablet, oral instant-dissolving tablet and preparation method thereof, to improve the ease for use and the convenience of stavudine oral formulations.
Stavudine is one of common drug in the anti-AIDS treatment HAART, belongs to efabirenz, and recommends to be used for children.Body weight surpasses 60 kilograms of adult recommended dose 40mg (bid), and body weight is lower than 60 kilograms of adult recommended dose 30mg (bid), takes medicine 12 hours at interval for twice.Above, body weight of 3 monthly ages is lower than child's recommended dose per kilogram of body weight 1mg (bid) of 30 kilograms, and body weight surpasses 30 kilograms of children and recommends the dosage of being grown up, the corresponding minimizing dosage of renal damage person.
Stavudine, its chemistry 1-by name (5-Hydroxymethy1-2,5-dihydro-furan-2-y1)-5-methy1-1H-pyrimidine-2,4-dione, structural formula is as follows:
The preparation supplementary material:
Stavudine dispersible tablet of the present invention and oral instant-dissolving tablet are except the principal agent stavudine, also comprise pharmaceutic adjuvant, wherein be decided to be 0.1-95% with he husband of weight percent content Cheese, pharmaceutic adjuvant is 5-99.9%, preferred stavudine content 2%-30%, pharmaceutic adjuvant 70-98%, pharmaceutic adjuvant comprise disintegrating agent 3%-70%, wet adhesive 0%-5%, lubricant 0.5%-5%, correctives 0%-2%, surfactant 0%-2%, surplus is a filler, each content and be 100%.The preparation specification is 1-200mg.
Stavudine oral cavity disintegration tablet of the present invention is except the principal agent stavudine, also comprise pharmaceutic adjuvant, wherein be decided to be 0.1-95% with he husband of weight percent content Cheese, pharmaceutic adjuvant is 5-99.9%, preferred stavudine content 2%-30%, pharmaceutic adjuvant 70-98%, pharmaceutic adjuvant comprises disintegrating agent 3%-70%, effervescent 0.5%-10%, wet adhesive 0%-5%, lubricant 0.5%-5%, correctives 0%-2%, surfactant 0%-2%, surplus is a filler, each content and be 100%.The preparation specification is 1-200mg.
The key of dispersible tablet, oral instant-dissolving tablet and oral cavity disintegration tablet is the disintegration rate in water, so it is extremely important that the disintegrating agent system in the tablet is selected, the disintegrating agent that the present invention selects is one or more in carboxymethyl starch sodium (CMS-Na), crosslinked carboxymethyl fecula sodium (cCMS-Na), low-substituted hydroxypropyl cellulose (LHPC), crospolyvinylpyrrolidone (PVPP), AmberliteIRP-88, sodium carboxymethyl cellulose (CMC-Na), cross-linking sodium carboxymethyl cellulose (cCMC-Na), carboxymethylcellulose calcium, the microcrystalline Cellulose (MCC).
Filler is in order to increase the weight and volume of tablet, be beneficial to molding and formulate drug dose, the filler in dispersible tablet of the present invention, oral instant-dissolving tablet and the oral cavity disintegration tablet comprises one or more in lactose, sucrose, mannitol, sorbitol, starch, pregelatinized Starch, cellulose, processing agar, gelatin or the dextrin.
Wet adhesive is to be convenient to granulate and the adherent pharmaceutic adjuvant of tabletting, and the binding agent of dispersible tablet, oral instant-dissolving tablet and oral cavity disintegration tablet comprises the water of one or more adjuvants in water, ethanol, tween 80, polyvinylpyrrolidone (PVP), hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium alginate, aluminium-magnesium silicate, arabic gum or the Polyethylene Glycol or the solution of alcohol among the present invention.
The lubricant that uses in dispersible tablet, oral instant-dissolving tablet and the oral cavity disintegration tablet among the present invention comprises one or more in magnesium stearate, calcium stearate, stearic acid, Polyethylene Glycol, silicon dioxide, micropowder silica gel, Pulvis Talci, aluminium hydroxide, the Stepanol MG.
Surfactant in the invention is one or more in sodium lauryl sulphate, cetyl sulfo-sodium succinate, sodium dioctyl sulfosuccinate, the tween 80.
The correctives that uses in the invention comprises that A Siba is sweet, in glycyrrhizin, stevioside or saccharin sodium, the medicinal essence one or more.
Also effervescent be can use in the oral cavity disintegration tablet, sodium bicarbonate, potassium bicarbonate, citric acid, tartaric acid or potassium hydrogen tartrate comprised.
The preparation method of stavudine dispersible tablet, oral instant-dissolving tablet comprises raw material pulverizing, weighing mixing, granulation, sheeting process, and concrete processing step is as follows:
Method one:
Step 1: with stavudine and various adjuvant pulverize separately, cross the 50-120 mesh sieve then, preserve standby respectively;
Step 2: take by weighing stavudine by recipe quantity, take by weighing various adjuvants by accessory formula, and with its abundant mix homogeneously;
Step 3: above-mentioned mixed uniformly component is sent into tablet machine, carry out tabletting.
Method two:
Step 1: with stavudine and various adjuvant pulverize separately, cross the 50-120 mesh sieve then, preserve standby respectively;
Step 2: take by weighing stavudine by recipe quantity, take by weighing filler and the disintegrating agent of partly measuring by accessory formula, and with its abundant mix homogeneously;
Step 3: with above-mentioned mixed uniformly component, adopt wet granulation, under 40-80 ℃ temperature, dry granulate then;
Step 4: in above-mentioned granule, add the disintegrating agent of surplus and other adjuvant in the accessory formula, fully mix homogeneously;
Step 5 is sent the granule of above-mentioned mix homogeneously into tablet machine, carries out tabletting.
In this method, add in the disintegrating agent and the ratio of adding is 20%-80%.
The preparation method of stavudine oral cavity disintegration tablet comprises raw material pulverizing, weighing mixing, granulation, sheeting process, and concrete processing step is as follows:
Method one:
Step 1: with stavudine and various adjuvant pulverize separately, cross the 50-120 mesh sieve then, preserve standby respectively;
Step 2: take by weighing stavudine by recipe quantity, take by weighing various adjuvants by accessory formula, and with its abundant mix homogeneously;
Step 3: above-mentioned mixed uniformly component is sent into tablet machine, carry out tabletting.
Method two:
Step 1: with stavudine and various adjuvant pulverize separately, cross the 50-120 mesh sieve then, preserve standby respectively;
Step 2: take by weighing stavudine by recipe quantity, take by weighing filler and disintegrating agent and the effervescent partly measured by accessory formula, and with its abundant mix homogeneously;
Step 3: with above-mentioned mixed uniformly component, adopt wet granulation, under 40-60 ℃ temperature, dry granulate then;
Step 4: in above-mentioned granule, add the disintegrating agent of surplus and other adjuvant in the accessory formula, fully mix homogeneously;
Step 5 is sent the granule of above-mentioned mix homogeneously into tablet machine, carries out tabletting.
In this method, add in the disintegrating agent and the ratio of adding is 20%-80%
Method three:
Step 1: with stavudine and various adjuvant pulverize separately, cross the 50-120 mesh sieve then, preserve standby respectively;
Step 2: take by weighing stavudine by 50% recipe quantity, take by weighing filler, disintegrating agent, sedan-chair flavor agent and acid effervescent by 50% accessory formula, and with its abundant mix homogeneously;
Step 3: take by weighing stavudine by 50% recipe quantity, take by weighing filler, disintegrating agent, sedan-chair flavor agent and alkaline effervescent by 50% accessory formula, and with its abundant mix homogeneously;
Step 4: with above-mentioned mixed uniformly component, adopt wet granulation respectively, under 40-80 ℃ temperature, dry granulate then;
Step 5: in above-mentioned granule, add the lubricant in the accessory formula, fully mix homogeneously;
Step 6: the granule of above-mentioned mix homogeneously is sent into tablet machine, carry out tabletting.
British Pharmacopoeia has been worked out the quality standard general rule to dispersible tablet, promptly dispersible tablet be can be in water homodisperse non-coated tablet; It should disintegrate within 3min in 19～21 ℃ of water except that the quality standard that should meet non-coated tablet; Put into 100ml water for 2 and be stirred to the screen cloth that the homogeneous dispersion that disperses the back to form fully can pass through 710 μ m apertures.Dispersible tablet and fuse, effervescent tablet are put into water all can disintegrate within 3min.Different is to form homogeneous dispersion after the dispersible tablet disintegrate, fuse formation solution, effervescent tablet formation solution or dispersion; Do not need effervescent (as carbonate and solid organic acid) and water soluble adjuvant in the prescription of dispersible tablet; Preparation technology is identical with general non-coated tablet, does not need the gentle relative humidity in control room; Take or swallow, chew clothes after can in water, disperseing.
According to the characteristics of dispersible tablet and oral instant-dissolving tablet, the starting point of prescription design be make tablet meet behind the water the short as far as possible time (＜3min) in disintegrate become very granule and form uniform suspension.Therefore, the dispersible tablet prescription has following characteristics among the present invention:
1, medicine and pharmaceutic adjuvant grain size category
The preparation method of dispersible tablet of the present invention and oral instant-dissolving tablet is close with the preparation method of conventional tablet, and principal agent and pharmaceutic adjuvant are processed pulverizing respectively, its fineness more than 80 orders, preferred 100 orders or 120 purpose granularities.
2, relatively large high-quality disintegrating agent and the suspending agent of use in conjunction
The high-quality disintegrating agent is meant the disintegrating agent of water absorption and swelling degree＞5ml/g.In dispersible tablet extensive use have that crosslinked carboxymethylstarch is received (cCMS-Na), the Resin A mberliteIRP-88 of low-substituted hydroxypropyl cellulose (L-HPC), crospolyvinylpyrrolidone (PVPP), cross-linked carboxymethyl cellulose sodium (cCMC-Na) and methacrylic acid and divinylbenzene copolymerization etc., wherein the swellbility 14.8ml/g of CMS-Na.Corn starch (swellbility 1.3ml/g), potato starch, microcrystalline Cellulose (MCC, swellbility 3.4ml/g) natural clay Magnesiumaluminumsilicate (Veegum) are then relatively poor as the disintegrating agent of dispersible tablet; Both mainly are as suspending agent for the backs.These material water absorption and swellings make disintegration of tablet, do not dissolve again after the swelling to form to be uniform aqueous suspension.Therefore, they have disintegrating agent and suspending agent dual function concurrently.Preferred crosslinked carboxymethylstarch is received (cCMS-Na), low-substituted hydroxypropyl cellulose (L-HPC), microcrystalline Cellulose, crospolyvinylpyrrolidone.
3, Nei Jia and add shared disintegrating agent
In add finger and before granulating, add, adding and add after referring to granulate.In dispersible tablet, have plenty of a kind of disintegrating agent and add also in both and add, as the inside and outside AmberliteIRP-88 that adds; Add a kind of disintegrating agent in having plenty of, add another kind,, add PVPP as the interior MCC that adds, in add cCMC-Na, add MCC ... or the like.Add disintegrating agent and make disintegration of tablet become coarse granule, play effect first; In add that then to make the disintegrate of coarse granule secondary be fine grained.Preferred inside and outside shared disintegrating agent.
4, adopt the solution of hydrophilic adhesive
Adopt hydrophilic adhesive, for example use polyvinylpyrrolidone (PVP), make granule after, particle surface becomes hydrophilic, behind the tabletting moisture be easy to moistening, penetrate, tablet is easy to disintegrate, also helps the stripping of medicine.Dispersible tablet adopts the dilute alcohol solution of PVP and hypromellose (HPMC) mostly, or with rare alcohol, water, seldom adopts starch slurry.Water or the dilute alcohol solution of preferred PVP.Solution concentration is at 0.1%-10%.
5, filler and correctives
Because dosage form is the oral quick release dosage form, the medicament mouthfeel is had relatively high expectations, so filler adopts mouthfeel mannitol preferably, can adopt lactose or pregelatinized Starch in addition.Correctives adopts that A Siba is sweet more, stevioside, essence.Correctives can add before granulation, also can be after granulation, add before the tabletting.
Country's medicine is examined the center and in the recent period the quality control and the research and development technology of oral cavity disintegration tablet has been drafted preliminary specification requirement.
Oral cavity disintegration tablet is that a kind of water that do not need in the oral cavity can disintegrate or dissolved tablet.Disintegration time in one minute, the first-selected water of medium, consumption should be less than 2ml, temperature is 37 ℃, adopts static method, and granularity control project (should less than the 710um of dispersible tablet) should be arranged in addition.
According to the formulation characteristic of oral cavity disintegration tablet, the prescription design has following characteristics among the present invention:
1, medicine and pharmaceutic adjuvant grain size category
The preparation method of oral cavity disintegration tablet sheet of the present invention is close with the preparation method of conventional tablet, and principal agent and pharmaceutic adjuvant are processed pulverizing respectively, its fineness more than 50 orders, preferred 100 orders or 120 purpose granularities.
2, select high-quality disintegrating agent and binding agent
These part characteristics are selected with the disintegrating agent and the binding agent of dispersible tablet among the present invention.
3, granulate
The method of granulating of conventional tablet has dry method and wet granulation, and two kinds of methods all can be implemented in the research of oral cavity disintegration tablet dosage form.Adopted the dry method direct compression among the present invention respectively, divided the oral cavity disintegration tablet that two parts are granulated respectively, the method for wet method one-step palletizing has been succeeded in developing stavudine according to the Acidity of Aikalinity wet method of effervescent.
4, effervescent
For accelerating the disintegration rate of oral cavity disintegration tablet, can add effervescent and promote its disintegrate.The effervescent that adopts has soda acid combinations such as sodium bicarbonate, potassium bicarbonate, citric acid, tartaric acid, potassium hydrogen tartrate.The combination of optimization citric acid and sodium bicarbonate among the present invention.The adding method of disintegrating agent and effervescent is divided before the pelletize and twice adding after the pelletize, and ratio is 20%-80% before and after it.
5, correctives and filler
Because dosage form is the oral quick release dosage form, the medicament mouthfeel is had relatively high expectations, so filler adopts mouthfeel mannitol and sorbitol preferably, can add lactose in addition.Correctives adopts that A Siba is sweet more, stevioside, essence.Correctives can add before granulation, also can be after granulation, add before the tabletting.
Technical characterstic of the present invention and superiority
The oral quick release dosage form that has prepared stavudine among the present invention, not only expanded the dosage form scope of stavudine, and prescription rationally, good, the no grittiness of inlet of disintegrating property and uncomfortable taste, preparation technology be easy, and utilize conventional tablet production equipment in the pharmaceuticals industry to get final product economy and produce high-quality dispersible tablet, oral instant-dissolving tablet or oral cavity disintegration tablet easily in enormous quantities.
The oral quick release dosage form infiltration rate of developing among the present invention is fast, thereby can improve the curative effect of bioavailability of medicament and blood drug level raising anti HIV-1 virus.
The stavudine oral quick release dosage form taking convenience that the present invention relates to, mouthfeel is good, runs into just disintegrate rapidly of saliva in the oral cavity, gives some old peoples, child or has the patient of the medicine obstacle of swallowing, water intaking inconvenience to provide convenience.
The specific embodiment:
Come the oral quick release dosage form of stavudine of the present invention done further specifying by the following examples, but do not represent the embodiment limitation of the present invention.
Dispersible tablet and oral instant-dissolving tablet:
Embodiment 1
Prescription:
The composition weight percent content
Stavudine 5%
cCMS-Na 6％
PVP (1% aqueous solution) 1%
Magnesium stearate 0.5%
All the other add to 100% for lactose
Preparation method:
Earlier above-mentioned material pulverize separately being crossed 100 mesh sieves, with stavudine, lactose, cCMS-Na mix homogeneously, is binding agent with the 1%PVP aqueous solution, and the system soft material is crossed 20 mesh sieves and granulated, 80 ℃ of oven dry, and 20 order granulate add magnesium stearate, mix homogeneously, tabletting.
Embodiment 2
Prescription:
The composition weight percent content
Stavudine 5%
CMS-Na 6％
PVP (1% aqueous solution) 1%
Magnesium stearate 0.5%
All the other add to 100% for mannitol
Preparation method:
Earlier above-mentioned material pulverize separately being crossed 100 mesh sieves, with stavudine, mannitol, 60%CMS-Na mix homogeneously, is binding agent with the 1%PVP aqueous solution, the system soft material, cross 20 mesh sieves and granulate 80 ℃ of oven dry, 20 order granulate, add residue 40%CMS-Na and magnesium stearate, mix homogeneously, tabletting.
Embodiment 3
The prescription weight percent content
Stavudine 3.5%
Pregelatinized Starch 20%
Microcrystalline Cellulose 10%
LHPC 6％
PVP (1% aqueous solution) 1%
Magnesium stearate 0.5%
All the other add to 100% for lactose
Preparation method:
Earlier above-mentioned material pulverize separately being crossed 100 mesh sieves, with stavudine, lactose, pregelatinized Starch, microcrystalline Cellulose, LHPC mix homogeneously, is binding agent with the 1%PVP aqueous solution, the system soft material, cross 20 mesh sieves and granulate 80 ℃ of oven dry, 20 order granulate, add magnesium stearate, mix homogeneously, tabletting.
Embodiment 4:
The prescription weight percent content
Stavudine 20%
cCMS-Na 6％
PVP (1% aqueous solution) 1%
Magnesium stearate 0.5%
All the other add to 100% for lactose
Preparation method:
Earlier above-mentioned material pulverize separately being crossed 100 mesh sieves, with stavudine, lactose, 60%cCMS-Na mix homogeneously, is binding agent with the 1%PVP aqueous solution, the system soft material, cross 20 mesh sieves and granulate 80 ℃ of oven dry, 20 order granulate, add residue 40%CMS-Na and magnesium stearate, mix homogeneously, tabletting.
Embodiment 5:
The prescription weight percent content
Stavudine 5%
Low-substituted hydroxypropyl cellulose 6%
cCMS-Na 5％
PVP (1% aqueous solution) 1%
Magnesium stearate 0.5%
Micropowder silica gel 1%
All the other add to 100% for mannitol
Preparation method:
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves, with stavudine, mannitol, 60%cCMS-Na, the abundant mix homogeneously of low-substituted hydroxypropyl cellulose, with 1%PVP aqueous solution (or alcoholic solution) is binding agent, the system soft material is crossed 20 mesh sieves and is granulated 80 ℃ of oven dry, 20 order granulate, add residue 40% crosslinked CMS-Na and magnesium stearate and micropowder silica gel, mix homogeneously, tabletting.
Embodiment 6:
The prescription weight percent content
Stavudine 3.5%
Low-substituted hydroxypropyl cellulose 6%
Crosslinked CMS-Na 5%
PVP (1% aqueous solution) 1%
Magnesium stearate 0.5%
Micropowder silica gel 1%
A Siba sweet 0.5%
Flavoring orange essence 0.5%
All the other add to 100% for mannitol
Preparation method;
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves, with stavudine, mannitol, 60% crosslinked CMS-Na, the abundant mix homogeneously of low-substituted hydroxypropyl cellulose, with 1%PVP aqueous solution (or alcoholic solution) is binding agent, the system soft material is crossed 20 mesh sieves and is granulated 80 ℃ of oven dry, 20 order granulate, add that residue 40% crosslinked CMS-Na, A Siba are sweet, flavoring orange essence and magnesium stearate and micropowder silica gel, mix homogeneously, tabletting.
The Performance Detection of each sample strip of gained among the embodiment;
| The sample title | Outward appearance | Hardness/kg | Disintegration s | Mouthfeel |
| 1 | Bright and clean | 4.2±0.3 | 115 | Generally |
| 2 | Bright and clean | 4.0±0.3 | 66 | Better |
| 3 | Bright and clean | 4.8±0.3 | 75 | Generally |
| 4 | Bright and clean | 4.0±0.3 | 42 | Generally |
| 5 | Bright and clean | 3.5±0.3 | 21 | Better |
| 6 | Bright and clean | 3.4±0.3 | 36 | Good |
More than among each embodiment sample strip all reached the requirement of disintegrate in the 3min that pharmacopeia requires, the difference according to using adjuvant respectively has advantage on medicine economic performance, mouthfeel, disintegration time, each evaluation index of hardness.
Oral cavity disintegration tablet:
Embodiment 7:
The prescription weight percent content
Stavudine 3.5%
Low-substituted hydroxypropyl cellulose 3%
Crospolyvinylpyrrolidone 5%
Sodium bicarbonate 1%
Citric acid 1%
Magnesium stearate 0.5%
Micropowder silica gel 1%
A Siba sweet 0.5%
Flavoring orange essence 0.5%
All the other add to 100% for mannitol
Preparation method:
Preparation method;
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves,, add magnesium stearate and micropowder silica gel at last, mix homogeneously, direct compression abundant mix homogeneously of above-mentioned each adjuvant such as stavudine, mannitol, crospolyvinylpyrrolidone, low-substituted hydroxypropyl celluloses.
Embodiment 8:
The prescription weight percent content
Stavudine 5%
Low-substituted hydroxypropyl cellulose 3%
Crospolyvinylpyrrolidone 10%
Tween 80 (1% ethanol solution) 1%
Sodium bicarbonate 1%
Citric acid 1%
Magnesium stearate 0.5%
Micropowder silica gel 1%
A Siba sweet 0.5%
Flavoring orange essence 0.5%
All the other add to 100% for mannitol
Preparation method;
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves, stavudine, mannitol, A Siba is sweet, flavoring orange essence, the crospolyvinylpyrrolidone of 75% recipe quantity, low-substituted hydroxypropyl cellulose, sodium bicarbonate, the abundant mix homogeneously of citric acid, add Tween 80 ethanol solution system soft material, crossing 20 mesh sieves granulates, 40 ℃ of oven dry down, add magnesium stearate and micropowder silica gel again behind the crospolyvinylpyrrolidone of adding residue recipe quantity, low-substituted hydroxypropyl cellulose, sodium bicarbonate, the citric acid mixing behind the granulate, mix homogeneously, direct compression.
Embodiment 9:
The prescription weight percent content
Stavudine 5%
Lactose 20%
Low-substituted hydroxypropyl cellulose 6%
Crospolyvinylpyrrolidone 5%
PVP 1％
Sodium bicarbonate 1%
Citric acid 1%
Magnesium stearate 0.5%
Micropowder silica gel 1%
A Siba sweet 0.5%
Flavoring orange essence 0.5%
All the other add to 100% for mannitol
Preparation method;
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves, the stavudine of 50% recipe quantity and mannitol, lactose, A Siba is sweet, flavoring orange essence, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose and sodium bicarbonate mix homogeneously, with PVP ethanol solution system soft material, cross 20 mesh sieves and granulate, 40 ℃ of oven dry down; The main materials and auxiliary materials and the abundant mix homogeneously of citric acid of other 50% recipe quantity, the ethanol solution system soft material of adding PVP is crossed 20 mesh sieves and is granulated, 40 ℃ of oven dry down, with the abundant mixing of two parts granule, add magnesium stearate and micropowder silica gel behind the granulate, mix homogeneously, direct compression.
Embodiment 10:
The prescription weight percent content
Stavudine 5%
Low-substituted hydroxypropyl cellulose 3%
cCMS-Na 5％
Sodium bicarbonate 5%
Citric acid 5%
Magnesium stearate 0.5%
Micropowder silica gel 1%
Stevioside 0.5%
A Siba sweet 0.5%
Flavoring orange essence 0.5%
All the other add to 100% for mannitol
Preparation method;
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves,, add magnesium stearate and micropowder silica gel at last, mix homogeneously, direct compression abundant mix homogeneously of above-mentioned each adjuvant such as stavudine, mannitol, cCMS-Na, low-substituted hydroxypropyl celluloses.
Embodiment 11:
The prescription weight percent content
Stavudine 10%
Microcrystalline Cellulose 8%
Low-substituted hydroxypropyl cellulose 3%
Crospolyvinylpyrrolidone 5%
PVP 1％
Sodium bicarbonate 1%
Citric acid 1%
Magnesium stearate 0.5%
Micropowder silica gel 1%
A Siba sweet 0.5%
Stevioside 0.5%
Flavoring orange essence 0.5%
All the other add to 100% for mannitol
Preparation method;
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves, the stavudine of 50% recipe quantity and mannitol, microcrystalline Cellulose, A Siba is sweet, stevioside, flavoring orange essence, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose and sodium bicarbonate mix homogeneously, with PVP ethanol solution system soft material, cross 20 mesh sieves and granulate, 40 ℃ of oven dry down; The main materials and auxiliary materials and the abundant mix homogeneously of citric acid of other 50% recipe quantity, the ethanol solution system soft material of adding PVP is crossed 20 mesh sieves and is granulated, 40 ℃ of oven dry down, with the abundant mixing of two parts granule, add magnesium stearate and micropowder silica gel behind the granulate, mix homogeneously, direct compression.
Embodiment 12:
The prescription weight percent content
Stavudine 5%
Low-substituted hydroxypropyl cellulose 6%
Microcrystalline Cellulose 10%
PVP 1％
Sodium bicarbonate 2%
Citric acid 2%
Magnesium stearate 0.5%
Micropowder silica gel 1%
A Siba sweet 0.5%
Flavoring orange essence 0.5%
All the other add to 100% for lactose
Preparation method;
Earlier above-mentioned material pulverize separately is crossed 100 mesh sieves,, add magnesium stearate and micropowder silica gel direct compression abundant mix homogeneously of above-mentioned each adjuvant such as stavudine, mannitol, microcrystalline Cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl celluloses.
The Performance Detection of each sample strip of gained among the embodiment;
| The sample title | Outward appearance | Hardness/kg | Disintegration s | Mouthfeel |
| 7 | Bright and clean | 2.0±0.3 | 23 | Good |
| 8 | Bright and clean | 2.3±0.3 | 18 | Good |
| 9 | Bright and clean | 2.2±0.3 | 16 | Good |
| 10 | Bright and clean | 2.2±0.3 | 26 | Good |
| 11 | Bright and clean | 3.5±0.3 | 28 | Good |
| 12 | Bright and clean | 3.8±0.3 | 35 | Better |
More than among each embodiment sample strip all reached the requirement of disintegrate in the 1min that requires, the difference according to using adjuvant respectively has advantage on medicine economic performance, mouthfeel, disintegration time, each evaluation index of hardness.
Claims (12)
1. oral preparation of quick releasing stavudine, be selected from oral cavity disintegration tablet, dispersible tablet and mouthful molten, it is characterized in that: its oral cavity disintegration tablet, dispersible tablet, oral instant-dissolving tablet are decided to be 0.1-95% with he husband of weight percent content Cheese, and pharmaceutic adjuvant is 5-99.9%; Dispersible tablet, oral instant-dissolving tablet:
Pharmaceutic adjuvant comprises disintegrating agent 3%-70%, wet adhesive 0%-5%, lubricant 0.5%-5%, correctives 0%-2%, surfactant 0%-2%; Surplus is a filler, and summation is 100%.
Oral cavity disintegration tablet:
Pharmaceutic adjuvant comprises disintegrating agent 3%-70%, effervescent 0.5%-10%, wet adhesive 0%-5%, lubricant 0.5%-5%, correctives 0%-2%, surfactant 0%-2%, and surplus is a filler, and summation is 100%.
2. oral preparation of quick releasing stavudine according to claim 1 is characterized in that: stavudine content 2%-30%, pharmaceutic adjuvant 70-98%.
3. oral preparation of quick releasing stavudine according to claim 1, it is characterized in that: disintegrating agent is one or more in carboxymethyl starch sodium, crosslinked carboxymethyl fecula sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, AmberliteIRP-88, sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, the microcrystalline Cellulose, and in the disintegrate promoter sodium lauryl sulphate, cetyl sulfo-sodium succinate, sodium dioctyl sulfosuccinate, tween 80 one or more.
4. oral preparation of quick releasing stavudine according to claim 1 is characterized in that:
Filler is one or more in lactose, sucrose, mannitol, sorbitol, starch, pregelatinized Starch, cellulose, processing agar, gelatin or the dextrin.
5. oral preparation of quick releasing stavudine according to claim 1 is characterized in that: wet adhesive is the water of one or more adjuvants in water, ethanol, tween 80, polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium alginate, aluminium-magnesium silicate, arabic gum or the Polyethylene Glycol or the solution of alcohol.
6. oral preparation of quick releasing stavudine according to claim 1 is characterized in that: wet adhesive is the water or the dilute alcohol solution of polyvinylpyrrolidone (PVP), and solution concentration is at 0.1%-10%.
7. oral preparation of quick releasing stavudine according to claim 1 is characterized in that: lubricant comprises one or more in magnesium stearate, calcium stearate, stearic acid, Polyethylene Glycol, silicon dioxide, micropowder silica gel, Pulvis Talci, aluminium hydroxide, the Stepanol MG.
8. oral preparation of quick releasing stavudine according to claim 1 is characterized in that: surfactant is one or more in sodium lauryl sulphate, cetyl sulfo-sodium succinate, sodium dioctyl sulfosuccinate, the tween 80.
9. oral preparation of quick releasing stavudine according to claim 1 is characterized in that: correctives is that A Siba is sweet, in glycyrrhizin, stevioside, saccharin sodium or the medicinal essence one or more.
10. oral preparation of quick releasing stavudine according to claim 1 is characterized in that: effervescent is sodium bicarbonate, potassium bicarbonate, citric acid, tartaric acid or potassium hydrogen tartrate.
11. the preparation method of an oral preparation of quick releasing stavudine is characterized in that: it is prescription according to claim 1 and ratio:
Step 1: with stavudine and various adjuvant pulverize separately, cross the 50-120 mesh sieve then, preserve standby respectively;
Step 2: take by weighing stavudine by recipe quantity, take by weighing filler and disintegrating agent and the effervescent partly measured by accessory formula, and with its abundant mix homogeneously;
Step 3: with above-mentioned mixed uniformly component, adopt wet granulation, under 40-60 ℃ temperature, dry granulate then;
Step 4: in above-mentioned granule, add the disintegrating agent of surplus and other adjuvant in the accessory formula, fully mix homogeneously;
Step 5 is sent the granule of above-mentioned mix homogeneously into tablet machine, carries out tabletting,
Add in the disintegrating agent and the ratio of adding is 20%-80%.
12. the preparation method of an oral preparation of quick releasing stavudine is characterized in that: it is prescription according to claim 1 and ratio:
Step 1: with stavudine and various adjuvant pulverize separately, cross the 50-120 mesh sieve then, preserve standby respectively;
Step 2: take by weighing stavudine by 50% recipe quantity, take by weighing filler, disintegrating agent, sedan-chair flavor agent and acid effervescent by 50% accessory formula, and with its abundant mix homogeneously;
Step 3: take by weighing stavudine by 50% recipe quantity, take by weighing filler, disintegrating agent, sedan-chair flavor agent and alkaline effervescent by 50% accessory formula, and with its abundant mix homogeneously;
Step 4: with above-mentioned mixed uniformly component, adopt wet granulation respectively, under 40-80 ℃ temperature, dry granulate then;
Step 5: in above-mentioned granule, add the abundant mix homogeneously of lubricant in the accessory formula;
Step 6: the granule of above-mentioned mix homogeneously is sent into tablet machine, carry out tabletting.
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