CN105616338A - Sodium valproate oral preparation slow-release preparation and preparation method thereof - Google Patents
Sodium valproate oral preparation slow-release preparation and preparation method thereof Download PDFInfo
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- CN105616338A CN105616338A CN201610061249.2A CN201610061249A CN105616338A CN 105616338 A CN105616338 A CN 105616338A CN 201610061249 A CN201610061249 A CN 201610061249A CN 105616338 A CN105616338 A CN 105616338A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
Abstract
The invention relates to a sodium valproate oral preparation slow-release preparation and a preparation method thereof and solves the technical problem of short efficacy maintaining time and the technical problems of poor taste and difficulty in administration by patients after medicine with undesirable peculiar smell is prepared into liquid preparations. The slow-release preparation contains sodium valproate and further contains ion exchange resin, microcapsule material, suspending agent and purified water, sodium valproate is adsorbed on the ion exchange resin to form microparticles which are wrapped by a coating material to form microcapsules, and the microcapsules are uniformly distributed in a liquid medium of the suspending agent and the purified water. The invention further provides a preparation method. The preparation method can be used for preparing the sodium valproate oral preparation slow-release preparation.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition containing sodium valproate and preparation method thereof, particularly relate to a kind of sodium valproate oral formulations body slow releasing preparation and preparation method thereof.
Background technology
Valproic acid was synthesized by Burton first in 1882, but until PierreEymard in 1962 chances on it in G.Carraz laboratory and has antiepileptic action, valproic acid is not had to be applied to the record of clinic, the clinical experiment of valproic acid sodium salt was made report in 1964 by Carraz et al. first, subsequently in 1967, first sodium valproate is listed by Sai Nuofei in France.
Valproic acid has applied as antiepileptic nearly 48 years, at present in the country's listing of more than 100, the whole world. Since valproic acid is introduced into clinic, as main antiepileptic, because it has various active, for treating the epilepsy of number of different types, curative effect obtains global generally acknowledged gradually. A large amount of clinical test results show, in the antiepileptic of all treatment children and adult epilepsy, it is widest in area that valproic acid is probably antiepileptic activity. Except treating partial and comprehensive epilepsy, research confirms, valproic acid can also effectively control the epilepsy syndromes of very refractory, for instance Lennox-Gastaut syndrome and West syndrome. Just because of this, in treatment symptom complicated type epilepsy patient rambunctious, valproic acid has very prominent advantage. Additionally, due to the antiepileptic activity scope of valproic acid is wide, being different from many other type of antiepileptics, therefore, the outbreak of any kind of epilepsy sample and epilepsy are all in the therapeutic domain of valproic acid.
Current sodium valproate oneself have multiple dosage form to list, such as tablet, capsule, oral solution, syrup, injection etc., wherein Sustained-release Sodium Valproate adult usual amounts: every day 600��1200mg, point take for 2��3 times; Children's's usual amounts: every day 20��30mg/kg, divide and take for 2��3 times, but not yet there is liquid slow-release preparation to study, if being prepared into liquid slow-release preparation, will increase applicable crowd (infant, gerontal patient), improve the compliance (be suitable for take, be easy to divided dose etc.) of clothes for patients.
Sustained-release preparation is the important directions of recent domestic medical industry development, and this dosage form can delay medicine absorption in vivo effectively, so that blood drug level is steady, reduce side effect, improves the effectiveness of medicine, safety and the compliance taken medicine. Wherein liquid slow-release preparation is more owing to its particular advantages having becomes the hot fields of research both at home and abroad. Many slow In Controlled-release Suspensions Usings oneself successfully list, as dromethan In Controlled-release Suspensions Using in nineteen eighty-two the U.S. list; Phenylpropanolamine, chlorphenamine compound controlled release suspensoid listed in the U.S. in 1984; Codeine, chlorphenamine compound controlled release suspensoid listed in the U.S. in 1985; Etodolac In Controlled-release Suspensions Using listed in Britain in 1993. Domestic begin with correlational study report in nineteen seventies, but do not have launch always, until domestic first liquid slow-release preparation dextromethorphan slow-release suspension in 2000 is gone into operation listing by Shanghai Hyundai Pharmacy stock Co., Ltd.
Liquid preparation has that absorption is fast, taking convenience and can administered in divided doses, easily by advantages such as child and old man accept. But the time that traditional liquid preparation maintains drug effect is short, and after having the medicine of smell to make liquid preparation, mouthfeel is poor, and patient is difficult to take, therefore research and develop that mouthfeel is good and to extend the liquid type slow releasing preparation of drug effect extremely urgent as children.
Summary of the invention
The present invention just in order to overcome prior art to maintain time of drug effect is short, have the medicine of smell to make liquid preparation after mouthfeel is poor, patient is difficult to the technical problem taken, it is provided that a kind of improve clothes for patients compliance (be suitable for take, be easy to divided dose etc.), the maintenance time length of drug effect, mouthfeel sodium valproate oral formulations body slow releasing preparation carefully and preparation method thereof.
For this, the present invention provides a kind of sodium valproate sustained-release oral preparation, and this release oral liquid contains sodium valproate, and sustained-release oral preparation is possibly together with ion exchange resin, microcapsule capsule material, suspending agent and purified water; Sodium valproate is adsorbed on ion exchange resin and forms microgranule, and microgranule is formed microcapsule by coating material encapsulation, and microcapsule is evenly distributed in the liquid medium of suspending agent and purified water.
Preferably, ion exchange resin is one of styrene alkalescence anion exchange resin, styrene strong basicity anion exchange resin, acrylic or methacrylic acid weak-base anion-exchange resin, polyethylene polyamine class weak-base anion-exchange resin, or two kinds or above mixture therein; Microcapsule capsule material is one of ethyl cellulose, hydroxyethyl cellulose, methylcellulose, polyacrylic resin, hydroxypropyl methylcellulose, Polyethylene Glycol, hydroxypropyl cellulose, or two kinds or above mixture therein; Suspending agent is arabic gum, sodium alginate, xanthan gum, MC, PVP, HPMC, the luxurious glue of Calculus Bovis from Northwest of China, one of Carbopol, AvicelRC591, or two kinds or above mixture therein.
Preferably, release oral liquid is possibly together with plasticizer, wetting agent. Plasticizer is one of in diethyl phthalate, dibutyl phthalate, Oleum Ricini, dibutyl sebacate, triacetin, tributyl citrate, PEG200, PEG400, propylene glycol, or two kinds or above mixture therein; Wetting agent is nonionic surfactant is one of polyoxyethylated alkyl phenol, polyoxyethylene aliphatic alcohol ether, polyoxyethylene polyoxypropylene block copolymer, or two kinds or above mixture therein.
Sodium valproate oral formulations body slow releasing preparation of the present invention is by sodium valproate, acceptable ion exchanger resin, microcapsule capsule material, plasticizer, suspending agent, purified water are prepared from, owing to the final dosage form of invented liposomes preparation is oral formulations body preparation, therefore, in the liquid medium of the present invention, comprise the preservative of routine dose, correctives and coloring agent.
The preparation method that present invention simultaneously provides a kind of sodium valproate sustained-release oral preparation, it comprises the steps: the preparation of (1) medicine carrying resin: under room temperature, adds ion exchange resin to sodium valproate aqueous solution, and constant temperature stirs, timing sampling, measures the concentration of drug in solution; After balance to be achieved, it is not associated with medicine with what deionized water washed away resin surface, is drying to obtain medicine carrying resin at 40-60 DEG C; (2) preparation of pastille microcapsule: adopt fluid bed bottom spraying type coating, medicine carrying resin is put in fluidising chamber, regulate air quantity, particle is made to be in desirable fluidized state in fluidising chamber, the coating solution containing plasticizer and microcapsule capsule material is at the uniform velocity pumped into constant flow pump, make coating solution atomizing effect good, continuous coating Non-intermittent drying time, it is ensured that substantially without adhesion phenomenon between micropartical in coating process; (3) preparation of sodium valproate oral formulations body slow releasing preparation: get it filled resin slow-releasing microcapsule, suspending agent, wetting agent, preservative, correctives, coloring agent, adds purified water, and namely mix homogeneously obtains sodium valproate oral formulations body slow releasing preparation.
Preferably, in step (1), the particle diameter of ion exchange resin is 30-150um; The concentration of sodium valproate aqueous solution is 100-1500mg/ml.
Preferably, in step (1), the particle diameter of ion exchange resin is 50-80um; The concentration of sodium valproate aqueous solution is 700-900mg/ml.
Preferably, in step (2), one of microcapsule capsule material ethyl cellulose, hydroxyethyl cellulose, methylcellulose, polyacrylic resin, hydroxypropyl methylcellulose, Polyethylene Glycol, hydroxypropyl cellulose, or above-mentioned in two kinds or above mixture; The consumption of microcapsule capsule material is that 0.5%-20%, w/w are for pastille dry resin; One of plasticizer material diethyl phthalate, dibutyl phthalate, Oleum Ricini, dibutyl sebacate, triacetin, tributyl citrate, PEG200, PEG400, propylene glycol or above-mentioned in two kinds or above mixture; The consumption of plasticizer is that 2%-20%, w/w are for microcapsule capsule material; The temperature of fluidized bed coating is 20-50 DEG C; The consumption of coating solution is that 2-5, v/w are for pastille dry resin; The solvent of coating solution is ethanol or water, or above-mentioned in the mixture of two kinds.
Preferably, in step (2), microcapsule capsule material is ethyl cellulose; The consumption of microcapsule capsule material is that 2%-7%, w/w are for pastille dry resin; Plasticizer material is dibutyl sebacate, tributyl citrate; The consumption of plasticizer is that 8%-10%, w/w are for microcapsule capsule material; The temperature of fluidized bed coating is 35-40 DEG C; The consumption of coating solution is that 3-4, v/w are for pastille dry resin; The solvent of coating solution is ethanol.
Preferably, in step (3), wetting agent includes alkyl sulfate, sulfonate, fatty acid or fatty acid ester sulfate, carboxylic acid soaps, phosphate ester selected from anionic surfactant; Nonionic surfactant includes polyoxyethylated alkyl phenol, polyoxyethylene aliphatic alcohol ether, polyoxyethylene polyoxypropylene block copolymer; The consumption of wetting agent is that 0.02%-0.1%, w/v are for suspensoid cumulative volume; The consumption of suspending agent is that 0.05%-2.0%, w/v are for suspensoid cumulative volume.
Preferably, in step (3), nonionic surfactant is tween 80; The consumption of wetting agent is that 0.03-0.05%, w/v are for suspensoid cumulative volume; The consumption of suspending agent is that 0.8-1.2%, w/v are for suspensoid cumulative volume.
The present invention adopts ion exchange resin switching technology, packaging technique, suspendible technology to prepare sodium valproate oral formulations body slow releasing preparation, sodium valproate is adsorbed on ion exchange resin and forms microgranule, microgranule is formed microcapsule by coating material, pastille microcapsule is evenly distributed on suspending agent and in the liquid medium of purified water, adds the oral formulations body slow releasing preparation that the preservative of routine dose, correctives and coloring agent obtain. The preparation method that this invention provides is simple, there is showing sustained release effect, reduce medicining times, reduce toxic and side effects, convenient for children and old people's medication, and good mouthfeel, can be used for the outbreak of any kind of epilepsy sample and epilepsy, solve the shortcomings such as existing Sodium Valproate poor compliance, it is suitable for the requirement of child, eliminate child's fear to medicine, improve the compliance of pediatric patient, meet the needs of child's clinical application.
Accompanying drawing explanation
Fig. 1 is the stripping curve in sodium valproate pastille microcapsule medium in vitro.
Detailed description of the invention
Below in conjunction with embodiment, the present invention will be further described.
Embodiment 1:
Formula:
Preparation technology:
1) preparation containing medicated resin: under room temperature, ion exchange resin is added the sodium valproate aqueous solution to 700mg/ml, constant temperature stirs, timing sampling, measures the concentration of drug in solution. After balance to be achieved, it is not associated with medicine with what deionized water washed away resin surface, is drying to obtain medicine carrying resin at 40-60 DEG C;
2) preparation of pastille microcapsule: adopt fluid bed bottom spraying type coating, medical resin is put in fluidising chamber, regulating air quantity makes particle be in desirable fluidized state in fluidising chamber, control temperature 20 DEG C, the coating solution containing plasticizer and microcapsule capsule material is at the uniform velocity pumped into constant flow pump, make coating solution atomizing effect good, continuous coating Non-intermittent drying time, it is ensured that substantially without adhesion phenomenon between micropartical in coating process;
3) preparation of sodium valproate oral formulations body slow releasing preparation: resin slow-releasing microcapsule of getting it filled, suspending agent, wetting agent, preservative, correctives, coloring agent, add purified water, namely mix homogeneously obtains sodium valproate oral formulations body slow releasing preparation.
Embodiment 2:
Formula:
Preparation technology:
1) preparation containing medicated resin: under room temperature, ion exchange resin is added the sodium valproate aqueous solution to 800mg/ml, constant temperature stirs, timing sampling, measures the concentration of drug in solution. After balance to be achieved, it is not associated with medicine with what deionized water washed away resin surface, is drying to obtain medicine carrying resin at 40-60 DEG C;
2) preparation of pastille microcapsule: adopt fluid bed bottom spraying type coating, medical resin is put in fluidising chamber, regulating air quantity makes particle be in desirable fluidized state in fluidising chamber, control temperature 35 DEG C, the coating solution containing plasticizer and microcapsule capsule material is at the uniform velocity pumped into constant flow pump, make coating solution atomizing effect good, continuous coating Non-intermittent drying time, it is ensured that substantially without adhesion phenomenon between micropartical in coating process;
3) preparation of sodium valproate oral formulations body slow releasing preparation: resin slow-releasing microcapsule of getting it filled, suspending agent, wetting agent, preservative, correctives, coloring agent, add purified water, namely mix homogeneously obtains sodium valproate oral formulations body slow releasing preparation.
Embodiment 3:
Formula:
Preparation technology:
1) preparation containing medicated resin: under room temperature, ion exchange resin is added the sodium valproate aqueous solution to 900mg/ml, constant temperature stirs, timing sampling, measures the concentration of drug in solution. After balance to be achieved, it is not associated with medicine with what deionized water washed away resin surface, is drying to obtain medicine carrying resin at 40-60 DEG C;
2) preparation of pastille microcapsule: adopt fluid bed bottom spraying type coating, medical resin is put in fluidising chamber, regulating air quantity makes particle be in desirable fluidized state in fluidising chamber, control temperature 40 DEG C, the coating solution containing plasticizer and microcapsule capsule material is at the uniform velocity pumped into constant flow pump, make coating solution atomizing effect good, continuous coating Non-intermittent drying time, it is ensured that substantially without adhesion phenomenon between micropartical in coating process;
3) preparation of sodium valproate oral formulations body slow releasing preparation: resin slow-releasing microcapsule of getting it filled, suspending agent, wetting agent, preservative, correctives, coloring agent, add purified water, namely mix homogeneously obtains sodium valproate oral formulations body slow releasing preparation.
Embodiment 4:
Formula:
Preparation technology:
1) preparation containing medicated resin: under room temperature, ion exchange resin is added the sodium valproate aqueous solution to 900mg/ml, constant temperature stirs, timing sampling, measures the concentration of drug in solution. After balance to be achieved, it is not associated with medicine with what deionized water washed away resin surface, is drying to obtain medicine carrying resin at 40-60 DEG C;
2) preparation of pastille microcapsule: adopt fluid bed bottom spraying type coating, medical resin is put in fluidising chamber, regulating air quantity makes particle be in desirable fluidized state in fluidising chamber, control temperature 40 DEG C, the coating solution containing plasticizer and microcapsule capsule material is at the uniform velocity pumped into constant flow pump, make coating solution atomizing effect good, continuous coating Non-intermittent drying time, it is ensured that substantially without adhesion phenomenon between micropartical in coating process;
3) preparation of sodium valproate oral formulations body slow releasing preparation: resin slow-releasing microcapsule of getting it filled, suspending agent, wetting agent, preservative, correctives, coloring agent, add purified water, namely mix homogeneously obtains sodium valproate oral formulations body slow releasing preparation.
Embodiment 5:
Formula:
Preparation technology:
1) preparation containing medicated resin: under room temperature, ion exchange resin is added the sodium valproate aqueous solution to 900mg/ml, constant temperature stirs, timing sampling, measures the concentration of drug in solution. After balance to be achieved, it is not associated with medicine with what deionized water washed away resin surface, is drying to obtain medicine carrying resin at 40-60 DEG C;
2) preparation of pastille microcapsule: adopt fluid bed bottom spraying type coating, medical resin is put in fluidising chamber, regulating air quantity makes particle be in desirable fluidized state in fluidising chamber, control temperature 30 DEG C, the coating solution containing plasticizer and microcapsule capsule material is at the uniform velocity pumped into constant flow pump, make coating solution atomizing effect good, continuous coating Non-intermittent drying time, it is ensured that substantially without adhesion phenomenon between micropartical in coating process;
3) preparation of sodium valproate oral formulations body slow releasing preparation: resin slow-releasing microcapsule of getting it filled, suspending agent, wetting agent, preservative, correctives, coloring agent, add purified water, namely mix homogeneously obtains sodium valproate oral formulations body slow releasing preparation.
Embodiment 6: tablets in vitro is tested
Adopt American Pharmacopeia 23 editions about the paddle method in slow releasing preparation vitro release algoscopy. Precision weighs the pastille microcapsule (being approximately equivalent to 300mg sodium valproate) of appropriate embodiment 1 preparation, by the phosphate buffer 500ml of pH6.8, is preheated to 37 �� 0.5 DEG C, and rotating speed is 100r min-1, add after sample, 1,2,3,4,5,6,8,10,12h sampling, supplement equivalent medium simultaneously. Essence takes subsequent filtrate 10ml, and add diethyl ether 10ml, according to dead-stop titration, uses 0.1mol L-1HCI liquid is titrated to galvanometer pointer nulling, and record consumes the volume of hydrochloric acid, calculates the cumulative release percentage amounts of slow releasing tablet according to titer. Result is shown in Fig. 1. Pastille microcapsule discharges comparatively fast in early days as shown in Figure 1, comparatively slow in the interphase release only having drug diffusion, plateau occurs at 10-12h, and its release in vitro has obvious slow releasing function.
Embodiment 7
The comparitive study of sodium valproate buffer solutions and traditional oral Solution In The Treatment epilepsy in childhood
1. data and method
Data: 60 example epileptics are divided into 2 groups with random sampling method, buffer solutions group 30 example, male 16 example, women 14 example, the age is (7.2 �� 1.8) one full year of life, and average attack rate is monthly 3 times, and average course of disease is 8 months; Matched group (conventional soln group) 30 examples, male 15 example, women 15 example, the age is (, 7.6 �� 1.2) one full year of life; Average attack rate is monthly 3 times, and average course of disease is 7 months.
Method: buffer solutions group gives the embodiment of the present invention 1 and prepares sodium valproate buffer solutions 30mg kg-1��d-1, every day is according to 30mg kg-1Oral 1 time, take continuously to effectively or not being resistant to; Matched group (conventional soln group) gives conventional sodium valproate solution 30mg kg-1��d-1, every day is according to 15mg kg-1It is administered orally points for 2 times, takes continuously to effectively or not being resistant to. Curative effect is observed after 16 weeks.
Curative effect determinate standard: basic controlling: seizure frequency minimizing reaches 100%, and epilepsy is not reaccessed; Effective: 100% > seizure frequency reduces >=75%; Effective: 75% > seizure frequency reduces >=50%; Invalid: seizure frequency reduces��25%. Total effective rate=control rate+obvious effective rate+effective percentage.
2. result
The clinical efficacy of 2.1 two kinds of oral administration solutions
Matched group (conventional soln group): basic controlling
Result is in Table 1:
The clinical efficacy of table 1 two types sodium valproate oral administration solution
| Group | Case load | Basic controlling rate | Obvious effective rate | Effective percentage | Total effective rate |
| Traditional oral solution | 30 | 20.0% | 33.3% | 26.7% | 80.0% |
| Release oral solution | 30 | 33.3% | 36.7% | 23.3% | 93.3% |
2.2 untoward reaction
Loss of appetite 2 example of feeling sick, liver function injury 1 example occur during traditional oral solution group medication, and there is dizzy drowsiness 1 example in the medication initial stage, and its adverse reaction rate is 13.3%; Loss of appetite 2 example of feeling sick occurs during release oral solution group medication, and liver function injury 1 example, its adverse reaction rate is 10%. Two groups of adverse reaction rates are close, but release oral solution group is lower.
3. conclusion
By studying proof above, the overall clinical efficacy rate (93.3%) of buffer solutions group to be substantially better than conventional soln group (80.0%), and adverse reaction rate is also below conventional soln group. Illustrate that sodium valproate release oral solution its clinical effectiveness in treatment epilepsy in childhood is substantially better than conventional soln agent, simultaneously take account of the particularity of children, owing to its medicining times is few, substantially increase child patient medication compliance, it is possible to as the choice drug of clinical treatment epilepsy in childhood.
Claims (10)
1. a sodium valproate sustained-release oral preparation, this release oral liquid contains sodium valproate, it is characterized in that, described sustained-release oral preparation is possibly together with ion exchange resin, microcapsule capsule material, suspending agent and purified water; Described sodium valproate is adsorbed on ion exchange resin and forms microgranule, and described microgranule is formed microcapsule by coating material encapsulation, and described microcapsule is evenly distributed in the liquid medium of suspending agent and purified water.
2. sodium valproate sustained-release oral preparation according to claim 1, it is characterized in that described ion exchange resin is one of styrene alkalescence anion exchange resin, styrene strong basicity anion exchange resin, acrylic or methacrylic acid weak-base anion-exchange resin, polyethylene polyamine class weak-base anion-exchange resin, or two kinds or above mixture therein;
Described microcapsule capsule material is one of ethyl cellulose, hydroxyethyl cellulose, methylcellulose, polyacrylic resin, hydroxypropyl methylcellulose, Polyethylene Glycol, hydroxypropyl cellulose, or two kinds or above mixture therein;
Described suspending agent is arabic gum, sodium alginate, xanthan gum, MC, PVP, HPMC, the luxurious glue of Calculus Bovis from Northwest of China, one of Carbopol, AvicelRC591, or two kinds or above mixture therein.
3. sodium valproate sustained-release oral preparation according to claim 1, it is characterised in that described release oral liquid is possibly together with plasticizer, wetting agent.
Described plasticizer is one of in diethyl phthalate, dibutyl phthalate, Oleum Ricini, dibutyl sebacate, triacetin, tributyl citrate, PEG200, PEG400, propylene glycol, or two kinds or above mixture therein;
Described wetting agent is nonionic surfactant: one of polyoxyethylated alkyl phenol, polyoxyethylene aliphatic alcohol ether, polyoxyethylene polyoxypropylene block copolymer, or two kinds or above mixture therein.
4. the preparation method of sodium valproate sustained-release oral preparation as claimed in claim 1, is characterized in that, comprise the steps:
(1) preparation of medicine carrying resin: under room temperature, adds ion exchange resin to sodium valproate aqueous solution, and constant temperature stirs, timing sampling, measures the concentration of drug in solution; After balance to be achieved, it is not associated with medicine with what deionized water washed away resin surface, is drying to obtain medicine carrying resin at 40-60 DEG C;
(2) preparation of pastille microcapsule: adopt fluid bed bottom spraying type coating, medicine carrying resin is put in fluidising chamber, regulate air quantity, particle is made to be in desirable fluidized state in fluidising chamber, the coating solution containing plasticizer and microcapsule capsule material is at the uniform velocity pumped into constant flow pump, make coating solution atomizing effect good, continuous coating Non-intermittent drying time, it is ensured that substantially without adhesion phenomenon between micropartical in coating process;
(3) preparation of sodium valproate oral formulations body slow releasing preparation: get it filled resin slow-releasing microcapsule, suspending agent, wetting agent, preservative, correctives, coloring agent, adds purified water, and namely mix homogeneously obtains sodium valproate oral formulations body slow releasing preparation.
5. the preparation method of sodium valproate sustained-release oral preparation according to claim 4, it is characterised in that in described step (1), the particle diameter of ion exchange resin is 30-150um; The concentration of described sodium valproate aqueous solution is 100-1500mg/ml.
6. the preparation method of sodium valproate sustained-release oral preparation according to claim 5, it is characterised in that in described step (1), the particle diameter of ion exchange resin is 50-80um; The concentration of sodium valproate aqueous solution is 700-900mg/ml.
7. the preparation method of sodium valproate sustained-release oral preparation according to claim 4, it is characterized in that in described step (2), microcapsule capsule material is one of ethyl cellulose, hydroxyethyl cellulose, methylcellulose, polyacrylic resin, hydroxypropyl methylcellulose, Polyethylene Glycol, hydroxypropyl cellulose, or above-mentioned in two kinds or above mixture; The consumption of microcapsule capsule material is that 0.5%-20%, w/w are for pastille dry resin; Plasticizer material be one of diethyl phthalate, dibutyl phthalate, Oleum Ricini, dibutyl sebacate, triacetin, tributyl citrate, PEG200, PEG400, propylene glycol or above-mentioned in two kinds or above mixture; The consumption of plasticizer is that 2%-20%, w/w are for microcapsule capsule material; The temperature of fluidized bed coating is 20-50 DEG C; The consumption of coating solution is that 2-5, v/w are for pastille dry resin; The solvent of coating solution is ethanol or water, or above-mentioned in the mixture of two kinds.
8. the preparation method of sodium valproate sustained-release oral preparation according to claim 7, it is characterised in that in described step (2), microcapsule capsule material is ethyl cellulose; The consumption of microcapsule capsule material is that 2%-7%, w/w are for pastille dry resin; Plasticizer material is dibutyl sebacate, tributyl citrate; The consumption of plasticizer is that 8%-10%, w/w are for microcapsule capsule material; The temperature of fluidized bed coating is 35-40 DEG C; The consumption of coating solution is that 3-4, v/w are for pastille dry resin; The solvent of coating solution is ethanol.
9. the preparation method of sodium valproate sustained-release oral preparation according to claim 4, it is characterized in that in described step (3), wetting agent includes polyoxyethylated alkyl phenol, polyoxyethylene aliphatic alcohol ether, polyoxyethylene polyoxypropylene block copolymer selected from nonionic surfactant; The consumption of wetting agent is that 0.02%-0.1%, w/v are for suspensoid cumulative volume; The consumption of suspending agent is that 0.05%-2.0%, w/v are for suspensoid cumulative volume.
10. the preparation method of sodium valproate sustained-release oral preparation according to claim 9, it is characterised in that in described step (3), wetting agent table is non-ionic surfactant Tween-80; The consumption of wetting agent is that 0.03-0.05%, w/v are for suspensoid cumulative volume; The consumption of suspending agent is that 0.8-1.2%, w/v are for suspensoid cumulative volume.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107998092A (en) * | 2016-10-28 | 2018-05-08 | 上海宣泰医药科技有限公司 | Medicament slow release unit, Orally disintegrating sustained release tablets comprising the medicament slow release unit and its preparation method and application |
| CN108272773A (en) * | 2018-03-14 | 2018-07-13 | 昆明理工大学 | Slow-release transdermal patch and the preparation method and application thereof containing sodium vedproate |
| CN109650489A (en) * | 2018-12-12 | 2019-04-19 | 安徽华塑股份有限公司 | The method for reducing chloride ion in salt making apparatus saliferous condensed water |
| CN113476400A (en) * | 2021-08-02 | 2021-10-08 | 成都倍特药业股份有限公司 | Sodium valproate oral solution and preparation method thereof |
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| CN108272773B (en) * | 2018-03-14 | 2019-09-27 | 昆明理工大学 | Slow-release transdermal patch and the preparation method and application thereof containing sodium vedproate |
| CN109650489A (en) * | 2018-12-12 | 2019-04-19 | 安徽华塑股份有限公司 | The method for reducing chloride ion in salt making apparatus saliferous condensed water |
| CN113476400A (en) * | 2021-08-02 | 2021-10-08 | 成都倍特药业股份有限公司 | Sodium valproate oral solution and preparation method thereof |
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