CN101884619B - Zolpidem tartrate controlled-release pellet and preparation method thereof - Google Patents
Zolpidem tartrate controlled-release pellet and preparation method thereof Download PDFInfo
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- CN101884619B CN101884619B CN2009100688773A CN200910068877A CN101884619B CN 101884619 B CN101884619 B CN 101884619B CN 2009100688773 A CN2009100688773 A CN 2009100688773A CN 200910068877 A CN200910068877 A CN 200910068877A CN 101884619 B CN101884619 B CN 101884619B
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Abstract
The invention provides an officinal composite containing zolpidem tartrate, and the weight of the active ingredients of the officinal composite is between 1mg and 20mg. The invention is characterized in that the officinal composite is a controlled-release pellet which mainly consists of a pill core and a controlled-release layer with a controlled-release function or consists of a faster-working quick-release outer layer part, a controlled-release layer maintaining slow release and a pill core. The preparation prepared by the invention can prolong drug release time by 6h and play roles in reducing blood concentration fluctuation and prolonging drug action time.
Description
Technical field
The invention belongs to the technical field of medicament slow release preparation, relate to a kind of slow-release micro-pill that contains the Zolpidemtar Trate active component and preparation method thereof in particular.
Background technology
Zolpidemtar Trate is the imidazopyridine sedative hypnotic, and its chemical constitution is all different with the known hypnotic of Benzodiazepines, barbiturates or other type.These article interact some pharmacological characteristics with BZ class with gamma aminobutyric acid-Benzodiazepines (GABA-BZ) receptor complex.In vitro tests shows, and is different with the mechanism of action of the non-selective combination of BZ class and exciting all ω receptor subtypes, through optionally with the combining of central nervous system's ω 1-receptor subtype, produce pharmacological action.ω 1-receptor mainly is present in IV layer, black substance, molecular layer of cerebellum, olfactory bulb, ventral thalamus complex, pons, inferior colliculus and the pallidum place of cortical sensibility motor region.These article almost do not have of flaccid muscles and anticonvulsant action in the zoopery.Maximum characteristics of these article and advantage are that he can keep people's SWS, and make the SWS sleep reduce unlike other sedative hypnotic.When low dose of, can shorten time for falling asleep, prolong the length of one's sleep; When heavy dose of, the 2nd sleep mutually, S sleep (the 3rd sleep mutually with the 4th) time lengthening, REM shortens the length of one's sleep.These article of we can say are a kind of good sedative hypnotic, and he keeps even prolonged SWS when prolonging patient length of one's sleep, has effectively improved patient's sleep quality.
The dosage form of the Zolpidemtar Trate that has gone on the market at present, has common oral preparation such as tablet, capsule and granule.The pharmacokinetics of Zolpidemtar Trate shows that its oral absorption is fast, and onset is rapid, and bioavailability is 70%, and in the therapeutic dose scope, shows linear kinetics, 0.3～3 hour blood drug level peaking in oral back.Eliminate half-life average out to 2.4 hours (0.7～3.5), effect can be kept 6 hours.Plasma protein binding rate is 92.5% ± 0.1%, and the first pass effect of liver is 35%.Adult's apparent volume of distribution is 0.54 ± 0.2L/kg, and the old people reduces to 0.34 ± 0.052L/kg.The equal non-activity of all metabolite, and by urine (56%) and feces (37%) discharge.Its conventional formulation specification is 5-10mg.
CN 1212838C discloses the controlled release form of zolpidem or its salt, is adapted in the scheduled time discharging according to two-way dissolution profiles, and wherein first be the rapid release phase mutually, and second mutually for the slow release phase and theirs is the particular embodiment that order gets to avoid abusing.Described its preparation method in the invention, it is characterized in that it is made up of the rapid onset of rapid release mutual-assistance syngignoscism multilayer tablet; Slow release is kept action time mutually, prolongs patient's length of one's sleep.
CN1660086 discloses the new drug administration approach-nasal-cavity administration of Zolpidemtar Trate.Described it in the invention and can have been absorbed preferably, avoided the oral first pass effect of hepar that brings, and owing to increased nauseating that gastrointestinal motility causes, side effect of digestive tract such as diarrhoea through nasal-cavity administration.
More than invention has all been set forth self preparation characteristic and to the requirement of right.The method for preparing of describing in the CN1212838C patent is comparatively complicated, and production equipment and technical staff are had relatively high expectations; Preparation process in the CN1660086 patent is complicated, and often drug loss is bigger in the practical application, and dosage is inaccurate.What the present invention described is the slow-release micro-pill preparation technology method of the simple easy operating of technology.
The blood concentration fluctuation of Zolpidemtar Trate common oral preparation is big, and the paddy p-ratio (T: PR) big, its removing half-life average out to 2.4h in blood hour, and be no more than 6h action time.In order to keep minimum activity, must improve dosage, long-term prescription possibly bring bigger side effect.Therefore developing the Zolpidem tartrate controlled-release preparation has very important significance.
Summary of the invention:
An object of the present invention is overcoming the shortcoming and defect of above-mentioned prior art; A kind of slow-release micro-pill that contains the Zolpidemtar Trate active component of novelty is provided; These article can comparatively fast discharge immediate release section in vivo; Medicine is absorbed rapidly plays syngignoscism, under the slow-released part effect, keep effective blood drug concentration, steady hypnotherapy needs can be provided.
Another object of the present invention provides a kind of slow-release micro-pill that contains the Zolpidemtar Trate active component, and slow-release micro-pill mainly is made up of two parts: contain pill core and slow release layer is formed.(see figure 1)
A further object of the present invention provides a kind of slow-release micro-pill that contains the Zolpidemtar Trate active component, and this slow-release micro-pill mainly is made up of three parts: contain pill core, slow release layer and pastille release layer and form (see figure 2).
The objective of the invention is to be achieved through following technical scheme:
1, a kind of slow-release micro-pill that contains the Zolpidemtar Trate active component; By containing pill core and slow release layer is formed; The weight ratio that contains pill core and slow release layer is (50mg-1000mg): (1.5mg-200mg); Preferably (100mg-500mg): (5mg-75mg), contain active component Zolpidemtar Trate 1mg-20mg in the slow-release micro-pill; Containing pill core can be to wrap the micropill that immediate release drug or medicine and adjuvant are mixed and made into by the basic ball of blank, and wherein, the weight ratio of medicine and adjuvant or blank basic ball is (1mg-20mg): (30mg-999mg), and preferred (5mg-15mg): (85mg-495mg).
2, a kind of slow-release micro-pill that contains the Zolpidemtar Trate active component; Also can form by containing pill core, slow release layer and pastille release layer; The weight ratio that contains pill core, slow release layer and pastille release layer is (50mg-1000mg): (1.5mg-200mg): (2.5mg-45mg); Preferably (100mg-500mg): (5mg-75mg): (4.5mg-30mg), contain active component Zolpidemtar Trate 1mg-20mg in the slow-release micro-pill; Containing pill core can be to wrap the micropill that immediate release drug or medicine and adjuvant are mixed and made into by the basic ball of blank, and the weight ratio of its Chinese medicine and adjuvant or blank basic ball is (1mg-20mg): (30mg-999mg); Preferably (5mg-15mg): (85mg-495mg); The pastille release layer is made up of medicinal materials such as medicine and methylcellulose or hypromellose or polyvidones, and its weight ratio is (2mg-15mg): (0.5mg-30mg); Preferably (3.5mg-10mg): (1mg-20mg).
Specifically comprise in the slow-release micro-pill of the present invention:
A, the pill core that contains of the present invention comprise: Zolpidemtar Trate, fillibility adjuvant, binding agent, lubricant etc., and wherein said fillibility adjuvant is molding adjuvants such as lactose, starch, microcrystalline Cellulose, sodium lauryl sulphate, sucrose, calcium phosphate, mannitol; Binding agent is adjuvants such as sucrose, methylcellulose, carboxymethyl cellulose, hypromellose, polyvidone, Macrogol 4000, Polyethylene Glycol-6000; Lubricant is pharmaceutically acceptable one or more compositions such as magnesium stearate, stearic acid, silicon dioxide and Pulvis Talci.
B, slow control layer of the present invention comprise: pharmaceutic adjuvants such as blocker, porogen, plasticizer, antiplastering aid, blocker wherein are acrylic resin, ethyl cellulose, cellulose acetate or cellulosic polymer etc.; Porogen is lactose, hypromellose, polyvidone, magnesium stearate or Pulvis Talci etc.; Plasticizer is triethyl citrate, diethyl phthalate, polyethylene glycol 6000, ATBC or dibutyl sebacate etc.; Antiplastering aid is silicon dioxide, Pulvis Talci, magnesium stearate or glyceryl monostearate etc.
Described slow release layer blocker acrylic resin is any one or a few the mixture in Youteqi S-100, RS30D, RL30D, RS100, RL100, NE30D, NE30D aqueous dispersion or RS30D and the RL30D aqueous dispersion etc.;
Described slow release layer blocker ethyl cellulose is ethyl cellulose powder or Aquacoat.
Described slow release layer blocker cellulosic polymer is cellulose acetate-phthalate (CAP), 1,2,4 benzenetricarboxylic acid cellulose acetate (CAT), succinic acid cellulose acetate (CAS), phthalic acid hypromellose (HPMCP), 1,2,4 benzenetricarboxylic acid hypromelloses (HPMCT) or succinic acid acetic acid hypromellose cellulose family enteric-coating material and their aqueous dispersions thereof such as (HPMCAS).
C, pastille release layer of the present invention comprise: Zolpidemtar Trate, methylcellulose or pharmaceutic adjuvant and or organic acid such as hypromellose or polyvidone.Organic acid is one or more of tartaric acid, citric acid, ethanedioic acid, malic acid and fumaric acid and their acid salt thereof.
A further object of the present invention has provided a kind of method for preparing that contains Zolpidemtar Trate active component slow-release micro-pill, comprises pastille base ball is placed fluid bed or coating pan, wraps slow release layer, is drying to obtain.Wherein, Containing the pill core segment can be to process micropill by Zolpidemtar Trate and after filling adjuvant, binding agent, mix lubricant, also can medicine be invested on the blank basic ball with methylcellulose or pharmaceutically acceptable medicinal materials spray such as hypromellose or polyvidone.Fill adjuvant and comprise one or more acid adjuvants of regulating such as organic acid of molding adjuvant such as lactose, starch, microcrystalline Cellulose or tartaric acid, citric acid, ethanedioic acid, malic acid and fumaric acid and their acid salt thereof; Binding agent comprises pharmaceutically acceptable medicinal materials such as sucrose, methylcellulose, hypromellose, polyvidone; Lubricant comprise magnesium stearate, stearic acid, colloidal silica, Pulvis Talci etc. pharmaceutically acceptable one or more.
For purposes such as attractive in appearance or the moistureproof lucifuge of moisture-resisting can attach general thin clothing layer in the outsourcing of pastille release layer.
Described general thin clothing layer is joined clothing liquid bag by methylcellulose or pharmaceutically acceptable medicinal materials such as hypromellose or polyvidone and is attached and form.Can contain pharmaceutically acceptable film material additives such as pigment, opacifier and plasticizer in its coating material.
Concrete method for preparing comprises the following steps:
(1) contain the preparation of pill core:
A. fillibility adjuvant and medicament mixed is even, add binding agent, play female also pill-rolling to required order with comminutor (or coating pan) and count 15-30 order (pill-rolling limit, limit adds lubricant), oven dry makes smooth ball-shaped and contains pill core.
B. with fillibility adjuvant mix homogeneously, add binding agent, play female also pill-rolling to required order with comminutor (or coating pan) and count 15-30 order (pill-rolling limit, limit adds lubricant); Oven dry; Make the blank basic ball of smooth ball, the basic ball of blank is placed fluid bed (or coating pan), make the temperature of basic ball be controlled at 35-60 ℃; With water or water and alcohol mixeding liquid, the skin that is coated on the blank basic ball of ball is processed and is contained pill core with Zolpidemtar Trate and hypromellose or polyvidone or methylcellulose.
(2) coating of slow release layer
To contain pill core and place fluid bed (or coating pan); Make the temperature of micropill be controlled at 20-50 ℃; Blocker, porogen, plasticizer, antiplastering aid are mixed with solution or suspension with water or water and alcohol mixeding liquid, are sprayed at the skin that contains pill core and process slow-release micro-pill.
(3) release layer coating
Slow-release micro-pill is placed fluid bed (or coating pan); Make the temperature of micropill be controlled at 20 ℃-50 ℃, with Zolpidemtar Trate, hypromellose or polyvidone or methylcellulose or and the water that is used of organic acid or water and alcohol mixeding liquid be mixed with solution or suspension and be coated on outer system.
The present invention compares with ordinary preparation according to the slow-release micro-pill of technical scheme 1 preparation has following characteristics:
(1) 20%-60% of the Zolpidemtar Trate total amount that discharges of 30 minutes slow-release micro-pill drug release determination initial stages makes drug effect; Slowly discharge residual drug in remaining time, this kind method for preparing can not cause that local blood concentration is too high and the situation in stimulating gastrointestinal road is kept effective blood drug concentration simultaneously.The deficiency that the blood drug level peak-to-valley ratio is excessive, action time is too short of having avoided ordinary preparation to exist has increased safety, has improved therapeutic effect.Dissolve total release time fully in 1-6 hour, preferred 1.5-5.0 hour.
(2) amass according to ball core different surface, adjust the size of drug loading, to reach required drug release rate; Also can reach required dissolution rate, in the design of formulation and technology, have flexible and changeable advantage through the mixed proportion and the spraying consumption of adjustment polymer.
(3) because the flowability of spheroidal micropill better, in the process of coating medicine and polymer, can obtain higher productive rate and repeatability, be easy to industrialization.
The present invention compares with ordinary preparation according to the slow-release micro-pill of technical scheme 2 preparations has following characteristics:
(1) the about 40%-70% of Zolpidemtar Trate that discharges of 30 minutes slow-release micro-pill drug release determination initial stages makes medicine onset at short notice; Slow-released part slowly discharges remaining, can not cause that local blood concentration is too high and the situation in stimulating gastrointestinal road is kept effective blood drug concentration simultaneously.The deficiency that the blood drug level peak-to-valley ratio is excessive, action time is too short of having avoided ordinary preparation to exist has increased safety, has improved therapeutic effect.Dissolve total release time fully in 1.5-6 hour, preferred 2.5-5.5 hour.
(2) slow-released part and immediate release section consubstantiality, avoided slow-released part to mix bringing with the immediate release section proportioning because the layering that weight factor causes makes preparation have potential safety hazard.
Description of drawings:
The Zolpidem tartrate controlled-release pellet sketch map of Fig. 1 application technology scheme 1 preparation.
The Zolpidem tartrate controlled-release pellet sketch map of Fig. 2 application technology scheme 2 preparations.
Fig. 3 Zolpidem tartrate controlled- release pellet embodiment 1,2 and 3 b stage gained micropill discharge 2h at the 0.1mol/L of 750ml hydrochloric acid solution earlier, add the release that continues to discharge in the sodium radio-phosphate,P-32 solution of the isothermal 0.2mol/L of the 250ml line of writing music subsequently.
The b stage gained micropill line of writing music of the release in the pH6.8 phosphate buffer of the 0.1mol/L hydrochloric acid solution of the water of 1000ml, 1000ml and 1000ml respectively among Fig. 4 Zolpidem tartrate controlled-release pellet embodiment 4.
B stage gained micropill earlier discharges 2h at the 0.1mol/L of 750ml hydrochloric acid solution among Fig. 5 Zolpidem tartrate controlled-release pellet embodiment 6, adds the release that continues to discharge in the sodium radio-phosphate,P-32 solution of the isothermal 0.2mol/L of the 250ml line of writing music subsequently.
The release of b stage gained micropill in the 0.1mol/L of the 1000ml hydrochloric acid solution line of writing music among Fig. 6 Zolpidem tartrate controlled-release pellet embodiment 9.
The release of c stage gained micropill in the 0.1mol/L of 1000ml hydrochloric acid solution of Fig. 7 Zolpidem tartrate controlled-release pellet embodiment 8 line of writing music.
The specific embodiment:
Below in conjunction with embodiment the present invention is further described.Embodiment is merely indicative content, means that never it limits scope of the present invention by any way.
A, contain the pill core composition
| Zolpidemtar Trate | 10g |
| Microcrystalline Cellulose | 80g |
| Calcium hydrogen phosphate | 40g |
| Pulvis Talci | 8g |
| 5% polyethylene glycol 6000 | 20g |
Method for preparing: take by weighing the supplementary material mix homogeneously by recipe quantity, add the binding agent mixing and process soft material; Play female also pill-rolling to required order with comminutor (or coating pan) and count the 15-30 order, oven dry, it is subsequent use to sift out best 18-25 order piller.
B. slow release layer composition
| Contain pill core | 100g |
| NE30D | 15g |
| Pulvis Talci | 2g |
| Distilled water | 30g |
Art for coating: take by weighing NE30D15g, Pulvis Talci 2g and distilled water 30g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 100g and place fluid bed, machine, regulating EAT is 30 ℃, and with the flow velocity of 5ml/min, the skin that is sprayed at the pastille piller is processed slow-release micro-pill.Taking-up adds an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 24h.Measure intermediate content, filling capsule.
A, contain the pill core composition
| Blank basic ball (16-20 order) | 200g |
| Zolpidemtar Trate | 15g |
| Tartaric acid | 4g |
| Hypromellose | 4g |
| Distilled water | 100g |
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and hypromellose are dissolved in the 100g distilled water; Get blank basic ball 200g in fluid bed, regulate 45 ℃ of EATs,, be sprayed at basic ball skin, dry 15 minutes, take out sieve and go fine powder subsequent use until having sprayed fully with the flow velocity of 7ml/min.
B. slow release layer composition
| Contain pill core | 180g |
| Youteqi L30D-55 | 50 |
| Pulvis Talci | 5g |
| Triethyl citrate | 3g |
| Distilled water | 100g |
Art for coating: take by weighing L30D-55 50g, Pulvis Talci 5g, triethyl citrate 3g and distilled water 100g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 180g and place fluid bed, machine, regulating EAT is 30 ℃, with the flow velocity of 6ml/min, carries out coating to finishing; Dry 15 minutes, take out and add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h.Measure intermediate content, filling capsule.
A, contain the pill core composition
| Blank basic ball (18-22 order) | 300g |
| Zolpidemtar Trate | 10g |
| Tartaric acid | 3g |
| Methylcellulose | 4g |
| Distilled water | 150 |
| Ethanol | 50 |
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and hypromellose are dissolved in distilled water and the alcoholic acid mixed solution; Get blank basic ball 300g in fluid bed, regulate 50 ℃ of EATs, make bed temperature remain 40-45 ℃,, be sprayed at basic ball skin, dry 15 minutes, take out sieve and go fine powder subsequent use until having sprayed fully with the flow velocity of 8ml/min.
B. slow release layer composition
| Contain pill core | 260g |
| Ethyl cellulose 25% aqueous dispersion | 80g |
| Hypromellose | 2.0g |
| Polyethylene glycol 6000 | 0.5g |
| Distilled water | 80g |
Art for coating: take by weighing ethyl cellulose 25% aqueous dispersion 80g, polyethylene glycol 6000 0.5g, hypromellose 2.0g and distilled water 80g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 260g and place fluid bed, machine, regulating EAT is 45 ℃, and bed temperature remains 35-40 ℃, with the flow velocity of 5ml/min, carries out coating to finishing; Taking-up adds an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 8h.Measure intermediate content, filling capsule.
A, contain the pill core composition
| Zolpidemtar Trate | 7.0g |
| Microcrystalline Cellulose | 100g |
| Lactose | 90g |
| Tartaric acid | 1.0g |
| 5% hypromellose | 40g |
Method for preparing: take by weighing the supplementary material mix homogeneously by recipe quantity, add the binding agent mixing and process soft material; Play female also pill-rolling to required order with comminutor (or coating pan) and count the 15-30 order, oven dry, it is subsequent use to sift out best 16-20 order piller.
B. slow release layer composition
| Contain pill core | 120g |
| RS100 | 15g |
| RL100 | 5g |
| Pulvis Talci | 3g |
| Diethyl phthalate | 0.3g |
| 90% ethanol | 200g |
Art for coating: take by weighing RS10D 20g, RL10D5g, diethyl phthalate 0.3g, Pulvis Talci 3g and 90% ethanol 200g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 120g and place fluid bed, machine, regulating EAT is 40 ℃, and bed temperature remains 35-40 ℃, with the flow velocity of 6ml/min, carries out coating to finishing; Taking-up adds an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h.
C. pastille release layer
| Slow-release micro-pill | 100g |
| Zolpidemtar Trate | 5g |
| Methylcellulose | 2g |
| Tartaric acid | 1g |
| Distilled water | 70g |
| Ethanol | 30g |
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, methylcellulose and tartaric acid, just dissolving; The pastille slow-release micropill is placed fluid bed, and reconciling temperature is 40 ℃, and the flow velocity with 6ml/min is sprayed onto end with medicinal liquid, measures intermediate content, filling capsule.
Embodiment 5 pastille 10mg Zolpidem tartrate controlled-release pellets
A, contain the pill core composition
| Zolpidemtar Trate | 4g |
| Microcrystalline Cellulose | 100g |
| Pregelatinized Starch | 50g |
| Magnesium stearate | 10g |
| 20% polyvidone | 25g |
Method for preparing: by recipe quantity take by weighing supplementary material mix all with, add the binding agent mixing and process soft material; Play female also pill-rolling to required order with comminutor (or coating pan) and count the 15-30 order, oven dry, it is subsequent use to sift out best 20-24 order piller.
B. slow release layer composition
| Contain pill core | 120g |
| RL30D | 15g |
| RS30D | 25g |
| ATBC | 4g |
| Pulvis Talci | 6g |
| Distilled water | 50g |
Art for coating: take by weighing RS30D25g, RL30D15g is mixed in the conical flask, grinds the Pulvis Talci with 6g with the 50g distilled water, stir down at magneton and pour into wherein, drip the 4g triethyl citrate at last, continue stirring 10 minutes, subsequent use; Take by weighing and contain pill core 120g and place fluid bed, machine, regulating EAT is 40 ℃, makes bed temperature keep 35 ℃, with the flow velocity of 6ml/min, carries out coating to finishing; Take out, add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 24h.
C. pastille release layer
| Slow-release micro-pill | 130g |
| Zolpidemtar Trate | 6g |
| Carboxymethyl cellulose | 2g |
| Distilled water | 70g |
| Ethanol | 30g |
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add carboxymethyl cellulose and make dissolving, add the uniform suspension of the ultrasonic formation of Zolpidemtar Trate again; The pastille slow-release micropill is placed fluid bed, and reconciling EAT is 50 ℃, and the flow velocity with 8ml/min is sprayed onto end with medicinal liquid, and dry the taking-up measured intermediate content, filling capsule.
A, contain the pill core composition
| Zolpidemtar Trate | 6g |
| Microcrystalline Cellulose | 150g |
| Mannitol | 80g |
| Sucrose | 40g |
| Magnesium stearate | 5g |
| 10% polyvidone | 50g |
Method for preparing: take by weighing the supplementary material mix homogeneously by recipe quantity, add the binding agent mixing and process soft material; Play female also pill-rolling to required order with coating pan and count the 16-25 order, oven dry, it is subsequent use to sift out best 18-22 order piller.
B. slow release layer composition
| Contain pill core | 220g |
| The 20%CAP aqueous dispersion | 120g |
| Dibutyl sebacate | 5g |
| Pulvis Talci | 5g |
| Glyceryl monostearate | 2g |
| Distilled water | 100g |
Art for coating: take by weighing 20%CAP aqueous dispersion 120g, dibutyl sebacate 5g, Pulvis Talci 5g, glyceryl monostearate 2g and distilled water 100g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 220g and place fluid bed, machine, regulating EAT is 45 ℃, makes bed temperature keep 40 ℃, with the flow velocity of 7ml/min, carries out coating to finishing; Taking-up adds an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 8h.
C. pastille release layer
| Slow-release micro-pill | 210g |
| Zolpidemtar Trate | 9g |
| Polyvidone | 8g |
| Citric acid | 3g |
| Distilled water | 150g |
| Ethanol | 50g |
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, polyvidone and citric acid and make dissolving; The pastille slow-release micropill is placed fluid bed, and reconciling temperature is 45 ℃, medicinal liquid is sprayed onto end, filling capsule.
A, contain the pill core composition
| Blank basic ball (18-24) | 120g |
| Zolpidemtar Trate | 2.5g |
| Ethanedioic acid | 1.5g |
| Hypromellose | 3g |
| Distilled water | 100g |
Method for preparing: recipe quantity Zolpidemtar Trate, ethanedioic acid and hypromellose are dissolved in the 100g distilled water; Get blank basic ball 120g in fluid bed, 55 ℃ of adjusting EATs with the flow velocity of 7ml/min, spray and basic ball skin, and hydrojet dry 10 minutes, is sieved and gone the fine powder taking-up subsequent use until fully.
B. slow release layer composition
| Contain pill core | 100g |
| Phthalic acid hypromellose (HPMCP) | 10g |
| Pulvis Talci | 4g |
| Polyvidone | 1g |
| 95% ethanol | 100g |
| Distilled water | 10g |
Art for coating: take by weighing phthalic acid hypromellose (HPMCP) 10g, Pulvis Talci 4g, polyvidone 1g, 95% ethanol 100g and distilled water 10g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 100g and place fluid bed, machine, regulating EAT is 50 ℃, carries out coating to finishing with the flow velocity of 5ml/min; Taking-up adds an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 6h.
C. pastille release layer
| Slow-release micro-pill | 80g |
| Zolpidemtar Trate | 2.5g |
| Macrogol 4000 | 2g |
| Distilled water | 50g |
| Ethanol | 50g |
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate and Macrogol 4000, make dissolving; The pastille slow-release micropill is placed fluid bed, and reconciling EAT is 40 ℃, and with the flow velocity of 9ml/min, spraying is outer with piller, and medicinal liquid is sprayed onto end, measures intermediate content, filling capsule.
Embodiment 8 pastille 10mg Zolpidem tartrate controlled-release pellets
A, contain the pill core composition
| Blank basic ball (20-25) | 200g |
| Zolpidemtar Trate | 5g |
| Polyvidone | 5g |
| Tartaric acid | 1.5g |
| Distilled water | 100g |
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and polyvidone are dissolved in the 100g distilled water; Get blank basic ball 200g in fluid bed, the adjusting air intake is 45 ℃ of temperature, with the flow velocity of 8ml/min, sprays and basic ball skin, and hydrojet dry 10 minutes, is sieved and gone the fine powder taking-up subsequent use until fully.
B. slow release layer composition
| Contain pill core | 180g |
| RS30D | 66g |
| Pulvis Talci | 6g |
| Lactose | 2g |
| Distilled water | 100g |
Art for coating: take by weighing RS30D66g, Pulvis Talci 8g, lactose 2g and distilled water 100g and stir mix homogeneously down in magneton, subsequent use; Take by weighing pastille piller 180g and place fluid bed, machine, regulating EAT is 35 ℃, carries out coating to finishing with the flow velocity of 5ml/min; Taking-up adds an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h.
C. pastille release layer
| Slow-release micro-pill | 200g |
| Zolpidemtar Trate | 5g |
| Methylcellulose | 2g |
| Tartaric acid | 0.5g |
| Distilled water | 70g |
| Ethanol | 30g |
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, methylcellulose and tartaric acid, make dissolving; The pastille slow-release micropill is placed fluid bed, and reconciling temperature is 40 ℃, with the flow velocity of 5ml/min medicinal liquid is sprayed onto end, after the drying, measures intermediate content, filling capsule.
Embodiment 9 pastille 15mg Zolpidem tartrate controlled-release pellets
A, contain the pill core composition
| Blank basic ball (25-30 order) | 300g |
| Zolpidemtar Trate | 10g |
| Tartaric acid | 2g |
| Hypromellose | 4g |
| Distilled water | 150 |
| Ethanol | 50 |
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and hypromellose are dissolved in distilled water and the alcoholic acid mixed solution; Get blank basic ball 300g in fluid bed, regulate 40 ℃ of EATs, extremely intact with the flow velocity hydrojet of 5ml/min, dry 15 minutes, it is subsequent use that sieve goes fine powder to take out.
B. slow release layer composition
| Contain pill core | 280g |
| Ethyl cellulose | 15g |
| Silicon dioxide | 2g |
| Magnesium stearate | 0.5g |
| 90% ethanol | 200g |
| Distilled water | 20g |
Art for coating: the ethyl cellulose that takes by weighing recipe quantity adds 90% ethanol ultrasonic dissolution, adds silicon dioxide, magnesium stearate and distilled water mix homogeneously under magneton stirs again, and is subsequent use; Take by weighing and contain pill core 280g and place fluid bed, machine, regulating EAT is 50 ℃, carries out coating to finishing with the flow velocity of 6ml/min; Taking-up adds an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 4h.
C. pastille release layer
| Slow-release micro-pill | 290g |
| Zolpidemtar Trate | 5g |
| Hypromellose | 2g |
| Distilled water | 100g |
| Ethanol | 100g |
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, hypromellose and tartaric acid, make dissolving; The pastille slow-release micropill is placed fluid bed, and reconciling EAT is 40 ℃, with the flow velocity of 5ml/min medicinal liquid is sprayed onto end, after the drying, measures intermediate content, filling capsule.
Embodiment 10 pastille 20mg Zolpidem tartrate controlled-release pellets
A, contain the pill core composition
| Blank basic ball (20-25) | 200g |
| Zolpidemtar Trate | 15g |
| Polyvidone | 5g |
| Tartaric acid | 2.0g |
| Distilled water | 100g |
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and polyvidone are dissolved in the 100g distilled water; Get blank basic ball 200g in fluid bed, the adjusting air intake is 45 ℃ of temperature, with the flow velocity of 8ml/min, sprays and basic ball skin, and hydrojet dry 10 minutes, is sieved and gone the fine powder taking-up subsequent use until fully.
B. slow release layer composition
| Contain pill core | 180g |
| NE30D | 60g |
| Pulvis Talci | 5g |
| Distilled water | 120g |
Art for coating: take by weighing NE30D60g, Pulvis Talci 5g and distilled water 120g and stir mix homogeneously down in magneton, subsequent use; Take by weighing pastille micropill 180g and place fluid bed, machine, regulating EAT is 30 ℃, carries out coating to finishing with the flow velocity of 5ml/min; Taking-up adds an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h.
C. pastille release layer
| Slow-release micro-pill | 200g |
| Zolpidemtar Trate | 5g |
| Polyvidone | 5g |
| Tartaric acid | 0.5g |
| Distilled water | 70g |
| Ethanol | 30g |
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, methylcellulose and tartaric acid, make dissolving; The pastille slow-release micropill is placed fluid bed, and reconciling temperature is 40 ℃, with the flow velocity of 5ml/min medicinal liquid is sprayed onto end, after the drying, measures intermediate content, filling capsule.
Embodiment 11 pastille 1mg Zolpidem tartrate controlled-release pellets
A, contain the pill core composition
| Blank basic ball (16-20 order) | 100g |
| Zolpidemtar Trate | 1g |
| Hypromellose | 4g |
| Distilled water | 100g |
Method for preparing: recipe quantity Zolpidemtar Trate and hypromellose are dissolved in the 100g distilled water; Get blank basic ball 100g in fluid bed, regulate 45 ℃ of EATs,, be sprayed at basic ball skin, dry 15 minutes, take out sieve and go fine powder subsequent use until having sprayed fully with the flow velocity of 5ml/min.
B. slow release layer composition
| Contain pill core | 180g |
| Youteqi L30D-55 | 20 |
| Pulvis Talci | 5g |
| ATBC | 4g |
| Distilled water | 100g |
Art for coating: take by weighing L30D-5520g, Pulvis Talci 5g, ATBC 4g and distilled water 100g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 180g and place fluid bed, machine, regulating EAT is 30 ℃, with the flow velocity of 6ml/min, carries out coating to finishing; Dry 15 minutes, take out and add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h.Measure intermediate content, filling capsule.
Embodiment 12 pastille 2.5mg Zolpidem tartrate controlled-release pellets
A, contain the pill core composition
| Blank basic ball (25-30 order) | 200g |
| Zolpidemtar Trate | 4.0g |
| Tartaric acid | 0.5g |
| Hypromellose | 2g |
| Distilled water | 80 |
| Ethanol | 20 |
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and hypromellose are dissolved in distilled water and the alcoholic acid mixed solution; Get blank basic ball 200g in fluid bed, regulate 40 ℃ of EATs, extremely intact with the flow velocity hydrojet of 5ml/min, dry 15 minutes, it is subsequent use that sieve goes fine powder to take out.
B. slow release layer composition
| Contain pill core | 180g |
| Ethyl cellulose | 12g |
| Silicon dioxide | 2g |
| Polyvidone | 0.2g |
| 90% ethanol | 200g |
| Distilled water | 20g |
Art for coating: the ethyl cellulose that takes by weighing recipe quantity adds 90% ethanol ultrasonic dissolution, adds silicon dioxide, polyvidone and distilled water mix homogeneously under magneton stirs again, and is subsequent use; Take by weighing and contain pill core 180g and place fluid bed, machine, regulating EAT is 50 ℃, carries out coating to finishing with the flow velocity of 6ml/min; Taking-up adds an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 4h.
C. pastille release layer
| Slow-release micro-pill | 180g |
| Zolpidemtar Trate | 0.5g |
| Hypromellose | 2g |
| Distilled water | 50g |
| Ethanol | 50g |
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, hypromellose and tartaric acid, make dissolving; The pastille slow-release micropill is placed fluid bed, and reconciling EAT is 40 ℃, with the flow velocity of 5ml/min medicinal liquid is sprayed onto end, after the drying, measures intermediate content, filling capsule.
Embodiment 13 drug release determination methods 1:
The Zolpidemtar Trate active component slow-release micro-pill that contains of the present invention has carried out the comparative experiments of release in vitro degree.
The drug release determination method:
These article of getting; According to drug release determination method [Chinese Pharmacopoeia version appendix in 2005 XD second method (1)], adopt dissolution method second subtraction unit, be dissolution medium with 0.1mol/L hydrochloric acid solution 750ml; Rotating speed is that per minute 50 changes; Operate the 5ml that takes a sample through 0.5h, 1h, 1.5h, 2h, centrifugal (3500 rev/mins) 5 minutes are got supernatant as test sample 1 in accordance with the law.Add isothermal 0.2mol/L sodium radio-phosphate,P-32 solution 250ml then, mixing continues timing and in 2.5h, 3h, 4h sampling, with the method operation, as test sample 2; Reference substance solution, it is an amount of to get Zolpidemtar Trate, and being made into concentration is that 10 μ g/ml hydrochloric acid solutions are as contrast liquid.According to ultraviolet spectrophotometry (Chinese Pharmacopoeia version appendix in 2005 IV A), measure absorbance in the 294nm wavelength, measure burst size.Embodiment 1,2,3 and 6 uses this method and measures, and concrete sampling time point is suitably adjustment as required.
Embodiment 14 drug release determination methods 2:
These article of getting are according to dissolution method (two appendix XC of Chinese Pharmacopoeia version in 2005, second method); 1000ml is a dissolution medium with water (or hydrochloric acid solution (9 → 1000) or pH6.8 phosphate buffer), 50 rev/mins of rotating speeds, operation in accordance with the law; Through 0.25h, 0.5h, 1h, 2h, 3h, 4h, 5h, 6h and 7h; Get solution 5ml, centrifugal (3500 rev/mins) 5 minutes are got supernatant as need testing solution.Reference substance solution, it is an amount of to get Zolpidemtar Trate, and being made into concentration is that 10 μ g/ml hydrochloric acid solutions are as contrast liquid.Measure absorbance according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2000) in the wavelength of 294nm, measure burst size.Embodiment 4,8 and 9 uses this method and measures, and concrete sampling time point is suitably adjustment as required.
Claims (12)
1. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Zolpidemtar Trate 10g;
Microcrystalline Cellulose 80g;
Calcium hydrogen phosphate 40g;
Pulvis Talci 8g;
5% polyethylene glycol 6000 20g;
Method for preparing: take by weighing the supplementary material mix homogeneously by recipe quantity, add the binding agent mixing and process soft material; Play female also pill-rolling to required order with comminutor or coating pan and count the 15-30 order, oven dry, it is subsequent use to sift out best 18-25 order piller;
B is a slow release layer, and composition is following:
Contain pill core 100g;
NE30D 15g；
Pulvis Talci 2g;
Distilled water 30g;
Art for coating: take by weighing NE30D 15g, Pulvis Talci 2g and distilled water 30g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 100g and place fluid bed, regulating EAT is 30 ℃, with the flow velocity of 5ml/min; Be sprayed at the skin that contains pill core and process slow-release micro-pill, take out and to add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 24h; Measure intermediate content, filling capsule.
2. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Blank basic ball 200g;
Zolpidemtar Trate 15g;
Tartaric acid 4g;
Hypromellose 4g;
Distilled water 100g;
Method for preparing: with recipe quantity Zolpidemtar Trate, tartaric acid and hypromellose solvent in the 100g distilled water; Get the blank basic ball of 200g16-20 order in fluid bed, regulating EAT is 45 ℃, with the flow velocity of 7ml/min, is sprayed at basic ball skin until having sprayed fully, dry 15 minutes, takes out sieve and goes fine powder subsequent use;
B is a slow release layer, and composition is following:
Contain pill core 180g;
Youteqi L30D-55 50g;
Pulvis Talci 5g;
Triethyl citrate 3g;
Distilled water 100g;
Art for coating: take by weighing Youteqi L30D-55 50g, Pulvis Talci 5g, triethyl citrate 3g and distilled water 100g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 180g and place fluid bed, regulating EAT is 30 ℃, with the flow velocity of 6ml/min, carries out coating to finishing; Dry 15 minutes, take out and add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h, measure intermediate content, filling capsule.
3. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Blank basic ball 300g;
Zolpidemtar Trate 10g;
Tartaric acid 3g;
Methylcellulose 4g;
Distilled water 150g;
Ethanol 50g;
Method for preparing: with recipe quantity Zolpidemtar Trate, tartaric acid and hypromellose solvent in distilled water and alcohol mixed solution; Get the blank basic ball of 300g18-22 order in fluid bed, regulating EAT is 50 ℃, makes bed temperature remain 40-45 ℃, with the flow velocity of 8ml/min, is sprayed at basic ball skin until having sprayed fully, dry 15 minutes, takes out sieve and goes fine powder subsequent use;
B is a slow release layer, and composition is following:
Contain pill core 260g;
Ethyl cellulose 25% aqueous dispersion 80g;
Hypromellose 2.0g;
Polyethylene glycol 6000 0.5g;
Distilled water 80g;
Art for coating: take by weighing ethyl cellulose 25% aqueous dispersion 80g, polyethylene glycol 6000 0.5g; , hypromellose 2.0g and distilled water 80g stir mix homogeneously down in magneton, and be subsequent use; Take by weighing and contain pill core 260g and place fluid bed, regulating EAT is 45 ℃, makes bed temperature remain 35-40 ℃, with the flow velocity of 5ml/min, carries out coating to finishing; Take out to add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 8h, measure intermediate content, filling capsule.
4. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Zolpidemtar Trate 7.0g;
Microcrystalline Cellulose 100g;
Lactose 90g;
Tartaric acid 1.0g;
5% hypromellose 40g;
Method for preparing: take by weighing the supplementary material mix homogeneously by recipe quantity, add the binding agent mixing and process soft material; Play female also pill-rolling to required order with comminutor or coating pan and count the 15-30 order, oven dry, it is subsequent use to sift out best 16-20 order piller;
B is a slow release layer, and composition is following:
Contain pill core 120g;
RS100 15g；
RL100 5g；
Pulvis Talci 3g;
Diethyl phthalate 0.3g;
90% ethanol 200g;
Art for coating: take by weighing RS100 15g, RL100 5g; , diethyl phthalate 0.3g, Pulvis Talci 3g and 90% ethanol 200g stir mix homogeneously down in magneton, and be subsequent use; Take by weighing and contain pill core 120g and place fluid bed, regulating EAT is 40 ℃, makes bed temperature remain 35-40 ℃, with the flow velocity of 6ml/min, carries out coating to finishing; Take out to add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h;
C is the pastille release layer, and composition is following:
Slow-release micro-pill 100g;
Zolpidemtar Trate 5g;
Methylcellulose 2g;
Tartaric acid 1.0g;
Distilled water 70g;
Ethanol 30g;
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, methylcellulose and tartaric acid, make dissolving; The pastille slow-release micropill is placed fluid bed, and regulating EAT is 40 ℃, and the flow velocity with 6ml/min is sprayed into end with medicinal liquid, measures intermediate content, filling capsule.
5. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Zolpidemtar Trate 4g;
Microcrystalline Cellulose 100g;
Pregelatinized Starch 50g;
Magnesium stearate 10g;
20% polyvidone 25g;
Method for preparing: take by weighing the supplementary material mix homogeneously in the prescription ratio, add the binding agent mixing and process soft material; Play female also pill-rolling to required order with comminutor or coating pan and count the 15-30 order, oven dry, it is subsequent use to sift out best 20-24 order piller;
B is a slow release layer, and composition is following:
Contain pill core 120g;
RL30D 15g
RS30D 25g；
Triethyl citrate 4g;
Pulvis Talci 6g;
Distilled water 50g;
Art for coating: take by weighing RS30D 25g, RL30D 15g is mixed in the conical flask, grind to stir down at magneton with the 50g distilled water and pour into wherein, drip the 4g triethyl citrate at last, continue stirring 10 minutes with the 6g Pulvis Talci, subsequent use; Take by weighing and contain pill core 120g and place fluid bed, regulating EAT is 40 ℃, makes bed temperature keep 35 ℃, carries out coating to finishing with the flow velocity of 6ml/min; Take out, add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 24h;
C is the pastille release layer, and composition is following:
Slow-release micro-pill 130g;
Zolpidemtar Trate 6g;
Carboxymethyl cellulose 2g;
Distilled water 70g;
Ethanol 30g;
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add carboxymethyl cellulose and make its dissolving, add the uniform suspension of the ultrasonic formation of Zolpidemtar Trate again; The pastille slow-release micropill is placed fluid bed, and regulating EAT is 50 ℃, and the flow velocity with 8ml/min is sprayed into end with medicinal liquid, and dry the taking-up measured intermediate content, filling capsule.
6. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Zolpidemtar Trate 6g;
Microcrystalline Cellulose 150g;
Mannitol 80g;
Sucrose 40g;
Magnesium stearate 5g;
10% polyvidone 50g;
Method for preparing: take by weighing the supplementary material mix homogeneously in the prescription ratio, add the binding agent mixing and process soft material; Play female also pill-rolling to required order with coating pan and count the 16-25 order, oven dry, it is subsequent use to sift out best 18-22 order piller;
B is a slow release layer, and composition is following:
Contain pill core 220g;
20%CAP aqueous dispersion 120g;
Dibutyl sebacate 5g;
Pulvis Talci 5g;
Glyceryl monostearate 2g;
Distilled water 100g;
Art for coating: take by weighing 20%CAP aqueous dispersion 120g, dibutyl sebacate 5g, Pulvis Talci 5g, glyceryl monostearate 2g and distilled water 100g mix homogeneously, subsequent use; Take by weighing and contain pill core 220g and place fluid bed, regulating EAT is 45 ℃, makes bed temperature keep 40 ℃, with the flow velocity of 7ml/min, carries out coating to finishing; Take out to add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 8h;
C is the pastille release layer, and composition is following:
Slow-release micro-pill 210g;
Zolpidemtar Trate 9g;
Polyvidone 8g;
Citric acid 3g;
Distilled water 150g;
Ethanol 50g;
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, polyvidone and citric acid and make its dissolving; The pastille slow-release micropill is placed fluid bed, and attemperation is 45 ℃, and medicinal liquid is sprayed into end, filling capsule.
7. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Blank basic ball 120g;
Zolpidemtar Trate 2.5g;
Ethanedioic acid 1.5g;
Hypromellose 3g;
Distilled water 100g;
Method for preparing: recipe quantity Zolpidemtar Trate, ethanedioic acid and hydroxypropyl cellulose are dissolved in the 100g distilled water; Get the blank basic ball 120g of 18-24 order and place fluid bed, regulating EAT is 55 ℃, with the flow velocity of 7ml/min, is sprayed at basic ball skin, and hydrojet dry 10 minutes, is sieved and gone fine powder subsequent use until fully;
B is a slow release layer, and composition is following:
Contain pill core 100g;
Phthalic acid hypromellose (HPMCP) 10g;
Pulvis Talci 4g;
Polyvidone 1g;
95% ethanol 100g;
Distilled water 10g;
Art for coating: take by weighing phthalic acid hypromellose (HPMCP) 10g, Pulvis Talci 4g, polyvidone 1g, 95% ethanol 100g and distilled water 10g mix homogeneously, subsequent use; Take by weighing and contain pill core 100g and place fluid bed, regulating EAT is 50 ℃, carries out coating to finishing with the flow velocity of 5ml/min; Take out to add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 6h;
C is the pastille release layer, and composition is following:
Slow-release micro-pill 80g;
Zolpidemtar Trate 2.5g;
Macrogol 4000 2g;
Distilled water 50g;
Ethanol 50g;
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate and Macrogol 4000, make its dissolving; The pastille slow-release micropill is placed fluid bed, and regulating EAT is 40 ℃, with the flow velocity of 9ml/min, is sprayed at the piller skin, and medicinal liquid is sprayed onto end, measures intermediate content, filling capsule.
8. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Blank basic ball 200g;
Zolpidemtar Trate 5g;
Polyvidone 5g;
Tartaric acid 1.5g;
Distilled water 100g;
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and polyvidone are dissolved in the 100g distilled water; Get the basic ball 200g of 20-25 order blank and place fluid bed, regulating EAT is 45 ℃, with the flow velocity of 8ml/min, is sprayed at basic ball skin, and hydrojet dry 10 minutes, is sieved and gone the fine powder taking-up subsequent use until fully;
B is a slow release layer, and composition is following:
Contain pill core 180g;
RS30D 66g；
Pulvis Talci 6g;
Lactose 2g;
Distilled water 100g;
Art for coating: take by weighing RS30D 66g, Pulvis Talci 6g, lactose 2g and distilled water 100g mix homogeneously, subsequent use; Take by weighing and contain pill core 180g and place fluid bed, regulating EAT is 35 ℃, carries out coating to finishing with the flow velocity of 5ml/min; Take out to add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h;
C is the pastille release layer, and composition is following:
Slow-release micro-pill 200g;
Zolpidemtar Trate 5g;
Methylcellulose 2g;
Tartaric acid 0.5g;
Distilled water 70g;
Ethanol 30g;
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, methylcellulose and tartaric acid, make dissolving; The pastille slow-release micropill is placed fluid bed, and attemperation is 40 ℃, with the flow velocity of 5ml/min medicinal liquid is sprayed onto end, after the drying, measures intermediate content, filling capsule.
9. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Blank basic ball 300g;
Zolpidemtar Trate 10g;
Tartaric acid 2g;
Hypromellose 4g;
Distilled water 150g;
Ethanol 50g;
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and hypromellose are dissolved in distilled water and the alcoholic acid mixed liquor; Get the blank basic ball 300g of 25-30 order and place fluid bed, regulating EAT is 40 ℃, and extremely intact with the flow velocity hydrojet of 5ml/min, dry 15 minutes, it is subsequent use that sieve goes fine powder to take out;
B is a slow release layer, and composition is following:
Contain pill core 280g;
Ethyl cellulose 15g;
Silicon dioxide 2g;
Magnesium stearate 0.5g;
90% ethanol 200g;
Distilled water 20g;
Art for coating: the ethyl cellulose that takes by weighing recipe quantity adds 90% ethanol ultrasonic dissolution, adds silicon dioxide, magnesium stearate and distilled water mix homogeneously under the stirring of magneton again, and is subsequent use; Take by weighing and contain pill core 280g and place fluid bed, regulating EAT is 50 ℃, carries out coating to finishing with the flow velocity of 6ml/min; Take out to add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 4h;
C is the pastille release layer, and composition is following:
Slow-release micro-pill 290g;
Zolpidemtar Trate 5g;
Hypromellose 2g;
Distilled water 100g;
Ethanol 100g;
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, hypromellose and tartaric acid, make dissolving; The pastille slow-release micropill is placed fluid bed, and regulating EAT is 40 ℃, with the flow velocity of 5ml/min medicinal liquid is sprayed onto end, after the drying, measures intermediate content, filling capsule.
10. Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Blank basic ball 200g;
Zolpidemtar Trate 15g;
Polyvidone 5g;
Tartaric acid 2.0g;
Distilled water 100g;
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and polyvidone are dissolved in the 100g distilled water; Get the basic ball 200g of 20-25 order blank and place fluid bed, the adjusting EAT is 45 ℃, with the flow velocity of 8ml/min, is sprayed at basic ball skin, does hydrojet until fully, dry 10 minutes, sieves and goes the fine powder taking-up subsequent use;
B is a slow release layer, and composition is following:
Contain pill core 180g;
NE30D 60g；
Pulvis Talci 5g;
Distilled water 120g;
Art for coating: take by weighing NE30D 60g, Pulvis Talci 5g and distilled water 120g and stir mix homogeneously down in magneton, subsequent use; Take by weighing and contain pill core 180g and place fluid bed, regulating EAT is 30 ℃, with the flow velocity of 5ml/min, carries out coating to finishing; Take out to add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h;
C is the pastille release layer, and composition is following:
Slow-release micro-pill 200g;
Zolpidemtar Trate 5g;
Polyvidone 5g;
Tartaric acid 0.5g;
Distilled water 70g;
Ethanol 30g;
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, polyvidone and tartaric acid, make dissolving; The pastille slow-release micropill is placed fluid bed, and attemperation is 40 ℃, with the flow velocity of 5ml/min medicinal liquid is sprayed onto end, after the drying, measures intermediate content, filling capsule.
11. a Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Blank basic ball 100g;
Zolpidemtar Trate 1g;
Hypromellose 4g;
Distilled water 100g;
Method for preparing: recipe quantity Zolpidemtar Trate and hypromellose are dissolved in the 100g distilled water; Get the blank basic ball 100g of 16-20 order and place fluid bed, regulating EAT is 45 ℃, with the flow velocity of 5ml/min, is sprayed at basic ball skin until having sprayed fully, dry 15 minutes, takes out sieve and goes fine powder subsequent use;
B is a slow release layer, and composition is following:
Contain pill core 180g;
Youteqi L30D-55 20g;
Pulvis Talci 5g;
ATBC 4g;
Distilled water 100g;
Art for coating: take by weighing Youteqi L30D-5520g, Pulvis Talci 5g, ATBC 4g and distilled water 100g and stir mix homogeneously down in Magnet, subsequent use; Take by weighing and contain pill core 180g and place fluid bed, regulating EAT is 30 ℃, with the flow velocity of 6ml/min, carries out coating to finishing; Dry 15 minutes, take out and add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 12h; Measure intermediate content, filling capsule.
12. a Zolpidem tartrate controlled-release pellet is characterized in that:
Wherein:
A is for containing pill core, and composition is following:
Blank basic ball 200g;
Zolpidemtar Trate 4g;
Tartaric acid 0.5g;
Hypromellose 2g;
Distilled water 80g;
Ethanol 20g;
Method for preparing: recipe quantity Zolpidemtar Trate, tartaric acid and hypromellose are dissolved in distilled water and the alcoholic acid mixed solution; Get the blank basic ball 200g of 25-30 order and place fluid bed, regulate 40 ℃ of EATs, extremely intact with the flow velocity hydrojet of 5ml/min, dry 15 minutes, it is subsequent use that sieve goes fine powder to take out;
B is a slow release layer, and composition is following:
Contain pill core 180g;
Ethyl cellulose 12g;
Silicon dioxide 2g;
Polyvidone 0.2g;
90% ethanol 200g;
Distilled water 20g;
Art for coating: the ethyl cellulose that takes by weighing recipe quantity adds 90% ethanol ultrasonic dissolution, adds silicon dioxide, polyvidone and distilled water mix homogeneously under magneton stirs again, and is subsequent use; Take by weighing and contain pill core 180g and place fluid bed, regulating EAT is 50 ℃, carries out coating to finishing with the flow velocity of 6ml/min; Take out to add an amount of Pulvis Talci mixing, in the tray in 40 ℃ of baking ovens dry 4h;
C is the pastille release layer, and composition is following:
Slow-release micro-pill 180g;
Zolpidemtar Trate 0.5g;
Hypromellose 2g;
Distilled water 50g;
Ethanol 50g;
Bag pharmaceutical worker skill: distilled water is mixed with ethanol, add Zolpidemtar Trate, hypromellose and tartaric acid, make dissolving; The pastille slow-release micropill is placed fluid bed, and regulating EAT is 40 ℃, with the flow velocity of 5ml/min medicinal liquid is sprayed onto end, after the drying, measures intermediate content, filling capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100688773A CN101884619B (en) | 2009-05-15 | 2009-05-15 | Zolpidem tartrate controlled-release pellet and preparation method thereof |
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| CN2009100688773A CN101884619B (en) | 2009-05-15 | 2009-05-15 | Zolpidem tartrate controlled-release pellet and preparation method thereof |
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| CN101884619A CN101884619A (en) | 2010-11-17 |
| CN101884619B true CN101884619B (en) | 2012-07-04 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102600090A (en) * | 2012-03-16 | 2012-07-25 | 北京阜康仁生物制药科技有限公司 | Dropping pill adopting zolpidem as major active ingredients and preparation method of dropping pill |
| CN103230381B (en) * | 2013-05-14 | 2014-12-17 | 中国药科大学 | Zolpidem tartrate time-selecting pulse sustained-release pellet and preparation method thereof |
| CN106806351A (en) * | 2017-03-30 | 2017-06-09 | 成都绿林科技有限公司 | A kind of preparation with zolpidem as main chemical compositions and preparation method thereof |
| CN108938601B (en) * | 2018-08-15 | 2021-10-08 | 珠海润都制药股份有限公司 | Metformin hydrochloride enteric-coated sustained-release pellet and preparation method thereof |
| CN110638791A (en) * | 2019-10-31 | 2020-01-03 | 浙江普利药业有限公司 | Topiramate sustained-release capsule and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1334729A (en) * | 1998-12-04 | 2002-02-06 | 圣诺菲-合成实验室公司 | Controlled-release dosage forms comprising zolpidem or salt thereof |
| CN1919197A (en) * | 2005-08-22 | 2007-02-28 | 天津药物研究院 | Slow release drop pills comprising toraesmide active ingredient and method for preparing same |
| WO2007103200A2 (en) * | 2006-03-02 | 2007-09-13 | Watson Pharmaceuticals, Inc. | Oral controlled release formulation for sedative and hypnotic agents |
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- 2009-05-15 CN CN2009100688773A patent/CN101884619B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1334729A (en) * | 1998-12-04 | 2002-02-06 | 圣诺菲-合成实验室公司 | Controlled-release dosage forms comprising zolpidem or salt thereof |
| CN1919197A (en) * | 2005-08-22 | 2007-02-28 | 天津药物研究院 | Slow release drop pills comprising toraesmide active ingredient and method for preparing same |
| WO2007103200A2 (en) * | 2006-03-02 | 2007-09-13 | Watson Pharmaceuticals, Inc. | Oral controlled release formulation for sedative and hypnotic agents |
Non-Patent Citations (1)
| Title |
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| 唐星.多层微丸缓释制剂.《口服缓控释制剂》.人民卫生出版社,2007,(第1版), * |
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| CN101884619A (en) | 2010-11-17 |
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