CN101904818A - Self-assembled composite membrane controlled sustained-release preparation and preparation method thereof - Google Patents
Self-assembled composite membrane controlled sustained-release preparation and preparation method thereof Download PDFInfo
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- CN101904818A CN101904818A CN201010245089XA CN201010245089A CN101904818A CN 101904818 A CN101904818 A CN 101904818A CN 201010245089X A CN201010245089X A CN 201010245089XA CN 201010245089 A CN201010245089 A CN 201010245089A CN 101904818 A CN101904818 A CN 101904818A
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Abstract
The invention belongs to the technical field of medicinal preparations, and in particular relates to a self-assembled composite membrane controlled sustained-release preparation and a preparation method thereof. The self-assembled composite membrane controlled sustained-release preparation comprises 2.5 to 67 percent of medicament, 12 to 76 percent of cationic polymer, 12 to 76 percent of anionic polymer and the balance of other auxiliary materials. Through the traditional process, matrix tablets or granules are prepared from polymers such as chitosan, sodium alga acid, carrageenan, sodium carboxymethylcellulose and the like with different charges; and in the releasing process, based on physiology pH change of a human body, two or more polymers with the different charges are reacted with each other to form an insoluble composite membrane on the surface of the tablet, and the matrix system is automatically converted into self-assembled composite membrane controlled sustained-release tablets or granules. The method can prepare medicaments with good controlled sustained-release effect by a simple process.
Description
Technical field
The invention belongs to medical technical field, particularly relate to self-assembled composite membrane controlled sustained-release preparation and preparation method thereof.
Background technology
At present commercially available sustained-release preparation is based on matrix type and film controlling type, and this two classes preparation respectively has advantage and deficiency.Skeleton type sustained release preparation mainly comprises with hydroxypropyl methylcellulose, starch, and carboxymethyl starch sodium, hydrophilic polymeies such as carbomer, and ethyl cellulose, stearic acid, water-insoluble such as stearyl alcohol or erodible material are the tablet of medicine carrying substrate preparation, granule etc.The characteristics of this class slow releasing preparation are that preparation technology is simple, but drug release behavior is subjected to the environment pH value, ionic strength, and condition influence such as enzyme are bigger.The basic preparation technology of film controlling type preparation is medicine and substrate is mixed in flakes, granule or micropill etc., wraps semi permeability clothing films such as ethyl cellulose, acrylic resin again by certain method.The film controlling type preparation generally can reach zero-order release, because coating membrane permeates gastro-intestinal Fluid, and restricted effect such as drug diffusion, so the drug release behavior of this class preparation generally depends on the character of film, and be subjected to the release medium environmental effect very little.But the shortcoming of film controlling type preparation is a complex process, needs to realize that through multistep cost is higher relatively.
Summary of the invention
Purpose of the present invention is exactly at above deficiency, the simple process that employing is easy to suitability for industrialized production prepares a kind of self-assembled composite membrane controlled sustained-release preparation, this slow releasing preparation is the matrix type preparation, after preparation enters human body, variation along with gastrointestinal tract pH value in the body, independently be converted into the film controlling type preparation, to reach good slow controlled-release effect.
The present invention uses cation type polymer to mix as slow releasing carrier of medication with anionic polymer, utilizes traditional direct powder compression, and technologies of preparing such as pelletizing press sheet are made the matrix type preparation.Because two kinds of polymer ionizing behavior difference under gastrointestinal tract pH changes, when preparation contact gastric juice, the surface cation type polymer is aquation and protonated gradually, and anionic polymer is in the unionized state, pH raises gradually along with the Digestive system environment, the anionic polymer of dosage surface ionizing gradually is electronegative, form water-insoluble complex film by electrostatic interaction or other active forces in dosage surface with positively charged cation type polymer, and the cation type polymer in the preparation kernel can not aquation and protonated because do not contact gastric juice, so there is not the generation of polyreaction in the label, label is the physical mixture of two kinds of polymer.Said preparation is converted into the film controlling type preparation automatically based on above former reason skeleton preparation, and drug release mainly is subjected to the property effect of the water-insoluble complex film of dosage surface, and it is little influenced by the stripping environmental change, therefore obtains the release effect same with coating class preparation.According to above-mentioned principle, preparation is in external self assembly coating process as shown in Figure 1: select the cation type polymer chitosan for use, the anionic polymer sodium alginate mixes compacting in flakes with the medicine theophylline, describe self assembly coating process by observing sheet in the cross section of different time points form.For ease of observing, the methyl orange of adding 0.5% is as coloring agent in the sheet powder.Dissolution medium is a 0-2h pH1.2 hydrochloric acid solution, and the 2-12hpH6.8 phosphate buffer changes with simulation gastro-intestinal Fluid pH.
The present invention is applicable to the various kinds of drug that dissolubility is different.For slightly molten or slightly soluble type medicine, said preparation is that a kind of drug release behavior is subjected to the gastrointestinal tract environment variable effect little, preparation that can constant speed release medicine; For insoluble drug, said preparation is an enteric slow release type preparation.
The resulting self-assembled composite membrane controlled sustained-release preparation of the present invention, each component are in dry, and percentage by weight is
Medicine 2.5-67%,
Cation type polymer 12-76%,
Anionic polymer 12-76%,
Other adjuvant surplus;
The preparation method of preparation: with medicine, cation type polymer, anionic polymer and other auxiliary materials and mixing, powder directly is pressed into tablet; Or granulate with methods such as dry method or wet methods, dry, granulate becomes granule or further compacting is in flakes.
Described cation type polymer is the chitosan that mean molecule quantity is not less than the different deacetylations of 100kDa; Described anionic polymer is the sodium alginate of molecular weight different mannuronic acid/guluronic acids (G/M) ratio of being not less than 100kDa (arbitrarily than), and molecular weight is not less than one of the carrageenan of 100kDa or sodium carboxymethyl cellulose that molecular weight is not less than 100kDa or its compositions.
One of described medicine is a theophylline, acetaminophen, and ligustrazine phosphate, aspirin, diclofenac sodium, in the glipizide.
Described other adjuvant is binding agent, lubricant, solubilizing agents for drugs, one of diluent etc. or its compositions commonly used in the pharmaceuticals industry.
Described binding agent can be selected from one or more in the following material: starch, microcrystalline Cellulose, polyvinylpyrrolidone, Polyethylene Glycol, ethanol etc.
Described lubricant can be selected from one or more in the following material: magnesium stearate, Pulvis Talci, micropowder silica gel, stearic acid, Polyethylene Glycol etc.
Described solubilizing agents for drugs is a sodium lauryl sulphate, one or more of materials such as poloxamer; Described diluent is a starch, lactose, sucrose, microcrystalline Cellulose, mannitol, Polyethylene Glycol, one or more in the materials such as polyvinylpyrrolidone.
In the described preparation method, corresponding granulation can be passed through the corresponding preparation moulding process then according to existing granulating process preparation such as dry method, wet method, spray drying, centrifugal granulating, can obtain corresponding slow releasing preparation.
Preparation technology of the present invention is simple, under the situation of change of gastrointestinal tract pH value, independently is converted into the film controlling type preparation in vivo, thereby reaches good slow controlled-release effect.
Can effectively realize the slow release of medicine in vivo for investigating chitosan/sodium alginate mixed-matrix, study the dog interior medicine dynamics of Theo-Dur.Adopt trial design to measure blood drug level-time graph in the body of taking theophylline-chitosan/sodium alginate Atrigel and commercially available Theo-Dur under the domesticated dog empty stomach state, and calculated the pharmacokinetic parameters of self-control and commercially available slow releasing tablet, according to the Wagner-Nelson method the two inside and outside drug release behavior has been carried out the dependency evaluation.
Dosage regimen and plasma sample acquisition method are as follows: two preparation trial design are adopted in test, and fasting 12h (can't help water) before the domesticated dog experiment takes a blood sample 1 time on an empty stomach, and single dose takes 1 in sample (being equivalent to theophylline 100mg).Dog is behind the oral test preparation, and respectively at 1,2,4,5,6,7,8,9,10,12,15,24,36h takes a sample, and blood sample is put respectively in the 5ml tool plug centrifuge tube that scribbles heparin, in the centrifugal 10min of 4000rmin-1, gets upper plasma and preserves standby in-20 ℃ of refrigerators.Get the blood plasma thawing before the mensuration,,, calculate blood drug level peak area ratio substitution standard curve by method operation sample introduction under " plasma sample processing method " item.3 dogs take reference preparation at the clean after date through 7d with method, get hematometry by identical method.
Reference preparation is with the blood drug level-time data reference preparation that is subjected to test preparation and be subjected to the blood drug level-time data of test preparation to see accompanying drawing 4.The computational methods of pharmacokinetic parameters are, Cmax, and tmax is a measured value, and area adopts trapezoidal method to calculate under the drug-time curve, and all the other parameters are used 3P87 computed in software, and the result is as shown in the table.
After the match of 3P87 software, be subjected to examination and reference preparation all to meet one compartment model by the judgement of AIC method.Because two groups of preparations all meet one compartment model, therefore adopt the Wagner-Nelson method to estimate the inside and outside dependency of preparation.Absorption fraction Fa and cumulative in vitro in the body that is tried with reference preparation are discharged percent Fd carry out linear regression respectively, equation is:
Fd%=1.2527Fa%+0.5255 (R=0.9679 is subjected to test preparation),
Fd%=1.4406Fa%-6.4532 (R=0.9638, reference preparation).
The result show be subjected to the examination with reference Theo-Dur inside and outside good relationship.The Theo-Dur that proof prepares as slow controlled release carrier with the CS/SA mixed-matrix can delay controlled release in vivo and discharge, and absorbs good in the body.
Description of drawings
The self assembly coating process of Fig. 1 preparation
0h matrix tablet (before the stripping);
Behind the 2h contact acid 2h, chitosan is in aquation positively charged state, and sodium alginate is in the unionized attitude;
After 6h changed the pH6.8 medium over to, sodium alginate ionizing gradually was electronegative, formed insoluble complexes membrane with the chitosan of surperficial positively charged by the static reaction; Chitosan in the label is not because contact acid can not positively charged, so label is the physical mixture of the two.The clear boundary of visible clothing film and label among the figure;
The 12h clothing film form that can be kept perfectly in process in leaching is insoluble to medium.
The slow releasing tablet that Fig. 2 contains theophylline in the simulation gastro-intestinal Fluid the stripping result and with the comparison of commercially available Theo-Dur
Fig. 3 contains the stripping result of slow releasing tablet in the simulation gastro-intestinal Fluid of other medicines
Blood drug level-time graph behind oral self-control theophylline-slow releasing tablet of Fig. 4 dog (embodiment 2) and the reference preparation
The specific embodiment
Theo-Dur
Theophylline 15.0g
Chitosan 7.1g
Sodium alginate 7.1g
Microcrystalline Cellulose 0.9g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves, with the equivalent method mixing that progressively increases, are pressed into the sheet of the heavy 300mg of average sheet.Described chitosan is molecular weight 400kDa, the chitosan of deacetylation 86.5%.Described sodium alginate is molecular weight 400kDa, and G/M is 40: 60 a sodium alginate.The stripping of preparation in the simulation gastro-intestinal Fluid the results are shown in accompanying drawing 2 (leaching condition is with accompanying drawing 1).
The Theo-Dur of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Theo-Dur
Theophylline 10.0g
Chitosan 6.6g
Sodium alginate 6.6g
Lactose 6.0g
Microcrystalline Cellulose 0.9g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves,, be pressed into the sheet of the heavy 300mg of average sheet with the equivalent method mixing that progressively increases.Described chitosan is molecular weight 400kDa, the chitosan of deacetylation 86.5%.Described sodium alginate is molecular weight 350kDa, and G/M is 40: 60 a sodium alginate.Lactose in the prescription can replace to starch, Macrogol 4000, polyethylene glycol 6000, sucrose, mannitol, any one in the polyvinylpyrrolidone.Preparation simulation in the gastro-intestinal Fluid the stripping result and relatively see accompanying drawing 2 (leaching condition is with accompanying drawing 1) with the stripping result of commercial preparation.
The Theo-Dur of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Embodiment 3
Theo-Dur/granule
Theophylline 15.0g
Chitosan 3.6g
Sodium carboxymethyl cellulose 10.5g
Microcrystalline Cellulose 0.9g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 mesh sieves, with theophylline, chitosan; sodium carboxymethyl cellulose and microcrystalline Cellulose are with the equivalent method mixing that progressively increases; with the soft material of 70% ethanol, cross 14 mesh sieves and granulate, place baking oven dry down at 30 ℃; cross 12 mesh sieve granulate; obtain sustained-release granular formulation, or, the granule that makes is sneaked into magnesium stearate by extruding method granulations such as round as a ball; be pressed into the sheet of the heavy 300mg of average sheet, obtain slow releasing tablet.Described chitosan is molecular weight 200kDa, the chitosan of deacetylation 86.5%.Described sodium carboxymethyl cellulose molecular weight is 330kDa.
The sustained-release theophylline preparation of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Theo-Dur
Theophylline 20.0g
Chitosan 4.6g
Sodium alginate 4.6g
Microcrystalline Cellulose 0.8g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves, with the equivalent method mixing that progressively increases, are pressed into the sheet of the heavy 300mg of average sheet.Described chitosan is molecular weight 370kDa, the chitosan of deacetylation 74%.Described sodium alginate is molecular weight 350kDa, and G/M is 30: 70 a sodium alginate.
The Theo-Dur of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Theo-Dur
Theophylline 10.0g
Chitosan 15.6g
Sodium alginate 3.6g
Microcrystalline Cellulose 0.8g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 mesh sieves, with the equivalent method mixing that progressively increases, are pressed into the sheet of the heavy 300mg of average sheet.Described chitosan is molecular weight 400kDa, the chitosan of deacetylation 86.5%.Described sodium alginate is molecular weight 200kDa, and G/M is 60: 40 a sodium alginate.
The Theo-Dur of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
The Glipizide enteric sustained-release sheet
Glipizide 0.5g
Chitosan 3.1g
Sodium alginate 15.2g
Sodium lauryl sulphate 0.6g
Microcrystalline Cellulose 0.6g
Magnesium stearate 0.02g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves,, be pressed into the sheet of the heavy 200mg of average sheet with the equivalent method mixing that progressively increases.Described chitosan is molecular weight 400kDa, the chitosan of deacetylation 86.5%.Described sodium alginate is molecular weight 350kDa, and G/M is 30: 70 a sodium alginate.The stripping of preparation in the simulation gastro-intestinal Fluid the results are shown in accompanying drawing 3 (leaching condition is with accompanying drawing 1).
The Glipizide enteric sustained-release sheet of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
The ligustrazine phosphoric acid sustained-release sheet
Ligustrazine phosphate 15.0g
Chitosan 6.0g
Carrageenan 4.0g
Sodium alginate 4.0g
Microcrystalline Cellulose 1.0g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 mesh sieves,, be pressed into the sheet of the heavy 300mg of average sheet with the equivalent method mixing that progressively increases.Described chitosan is molecular weight 300kDa, the chitosan of deacetylation 80%.Described carrageenan is the carrageenan of molecular weight 200kDa, and described sodium alginate is a molecular weight 345, and G/M is 45: 55 a sodium alginate.
The ligustrazine phosphoric acid sustained-release sheet of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
The ligustrazine phosphoric acid sustained-release sheet
Ligustrazine phosphate 15.0g
Chitosan 10.5g
Carrageenan 3.6g
Microcrystalline Cellulose 0.9g
Micropowder silica gel 0.03g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 mesh sieves,, be pressed into the sheet of the heavy 300mg of average sheet with the equivalent method mixing that progressively increases.Described chitosan is molecular weight 400kDa, the chitosan of deacetylation 86.5%.Described carrageenan is the carrageenan of molecular weight 120kDa.
The ligustrazine phosphoric acid sustained-release sheet of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
The ligustrazine phosphoric acid sustained-release sheet
Ligustrazine phosphate 3g
Chitosan 3.6g
Carrageenan 22.8g
Microcrystalline Cellulose 0.6g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves,, be pressed into the sheet of the heavy 300mg of average sheet with the equivalent method mixing that progressively increases.Described chitosan is molecular weight 400kDa, the chitosan of deacetylation 86.5%.Described carrageenan is the carrageenan of molecular weight 160kDa.
The ligustrazine phosphoric acid sustained-release sheet of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
The acetaminophen slow releasing tablet
Acetaminophen 15.0g
Chitosan 7.1g
Sodium carboxymethyl cellulose 7.1g
Microcrystalline Cellulose 0.9g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 mesh sieves,, be pressed into the sheet of the heavy 300mg of average sheet with the equivalent method mixing that progressively increases.Described chitosan is molecular weight 400kDa, and the chitosan of deacetylation 86.5%, the molecular weight of described sodium carboxymethyl cellulose are 330KDa.The stripping of preparation in the simulation gastro-intestinal Fluid the results are shown in accompanying drawing 3 (leaching condition is with accompanying drawing 1).
The acetaminophen slow releasing tablet of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Embodiment 11
Aspirin sustained release tablet
Aspirin 2.5g
Chitosan 22.8g
Sodium carboxymethyl cellulose 3.6g
Microcrystalline Cellulose 1.1g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves, with the equivalent method mixing that progressively increases, are pressed into the sheet of the heavy 300mg of average sheet.Described chitosan is molecular weight 400kDa, the chitosan of deacetylation 86.5%.Described sodium carboxymethyl cellulose molecular weight is 300kDa.
The aspirin sustained release tablet of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Aspirin sustained release tablet
Aspirin 15.0g
Chitosan 7.1g
Sodium alginate 7.1g
Microcrystalline Cellulose 0.9g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves,, be pressed into the sheet of the heavy 300mg of average sheet with the equivalent method mixing that progressively increases.Described chitosan is molecular weight 400kDa, and the chitosan of deacetylation 86.5%, described sodium alginate are molecular weight 350kDa, and G/M is 40: 60 a sodium alginate.The stripping of preparation in the simulation gastro-intestinal Fluid the results are shown in accompanying drawing 3 (leaching condition is with accompanying drawing 1).
The aspirin sustained release tablet of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Embodiment 13
Aspirin sustained release tablet
Aspirin 2.5g
Chitosan 3.9g
Sodium carboxymethyl cellulose 22.8g
Microcrystalline Cellulose 0.8g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves, with the equivalent method mixing that progressively increases, are pressed into the sheet of the heavy 300mg of average sheet.Described chitosan is molecular weight 300kDa, the chitosan of deacetylation 80%.Described sodium carboxymethyl cellulose molecular weight is 300kDa.
The aspirin sustained release tablet of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
The diclofenac sodium enteric-coated sustained-release tablet
Diclofenac sodium 2.5g
Chitosan 2.0g
Sodium alginate 10.0g
Microcrystalline Cellulose 0.45g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves,, be pressed into the sheet of the heavy 150mg of average sheet with the equivalent method mixing that progressively increases.Described chitosan is molecular weight 200kDa, the chitosan of deacetylation 83%.Described sodium alginate is molecular weight 350kDa, and G/M is 30: 70 a sodium alginate.The stripping of preparation in the simulation gastro-intestinal Fluid the results are shown in accompanying drawing 3 (leaching condition is with accompanying drawing 1).
The diclofenac sodium enteric-coated sustained-release tablet of making as stated above meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Theo-Dur
Theophylline 15.0g
Chitosan 7.1g
Sodium alginate 7.1g
Microcrystalline Cellulose 0.9g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 mesh sieves,, be pressed into the sheet of the heavy 150mg of average sheet with the equivalent method mixing that progressively increases.Described chitosan is molecular weight 400kDa, the chitosan of deacetylation 86.5%.Described sodium alginate is molecular weight 100kDa, and G/M is 40: 60 a sodium alginate.
The Theo-Dur of making as stated above, the dissolution test result does not meet the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Embodiment 16
The ligustrazine phosphoric acid sustained-release sheet
Ligustrazine phosphate 10.0g
Chitosan 15.6g
Carrageenan 3.6g
Microcrystalline Cellulose 0.8g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 sieves, with the equivalent method mixing that progressively increases, are pressed into the sheet of the heavy 300mg of average sheet.Described chitosan is molecular weight 100kDa, the chitosan of deacetylation 90%.Described carrageenan molecule amount is 95kDa.
The ligustrazine phosphoric acid sustained-release sheet of making as stated above, the dissolution test result does not meet the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Embodiment 17
Aspirin sustained release tablet
Aspirin 10.0g
Chitosan 15.6g
Sodium carboxymethyl cellulose 3.6g
Microcrystalline Cellulose 0.8g
Magnesium stearate 0.03g
Make 100
Preparation technology:
Medicine and adjuvant are crossed 100 mesh sieves, with the equivalent method mixing that progressively increases, are pressed into the sheet of the heavy 300mg of average sheet.Described chitosan is molecular weight 100kDa, the chitosan of deacetylation 90%.Described sodium carboxymethyl cellulose molecular weight is 97.5kDa.
The aspirin sustained release tablet of making as stated above, the dissolution test result does not meet the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Embodiment 18
Aspirin sustained release tablet
Aspirin 10.0g
Chitosan 8.4g
Sodium carboxymethyl cellulose 3.6g
Carrageenan 3.6g
Sodium alginate 3.6g
Microcrystalline Cellulose 0.8g
Magnesium stearate 0.03g
Make 100 preparation technologies:
Medicine and adjuvant are crossed 100 mesh sieves, with the equivalent method mixing that progressively increases, are pressed into the sheet of the heavy 300mg of average sheet.Described chitosan is molecular weight 400kDa, the chitosan of deacetylation 86%.Described sodium carboxymethyl cellulose molecular weight is 300kDa.Described carrageenan molecule amount is 160kDa.Described sodium alginate molecular weight is 350kDa, and G/M is 30: 70.
The aspirin sustained release tablet of making as stated above, the dissolution test result meets the requirement of the coherent detection project of regulation in " 2005 editions two ones of Chinese Pharmacopoeias " ' rules of preparations '.
Claims (10)
1. self-assembled composite membrane controlled sustained-release preparation, it is characterized in that: be made up of following material, each component is in dry, and percentage by weight is:
Medicine 2.5-67%,
Cation type polymer 12-76%,
Anionic polymer 12-76%,
Other adjuvant surplus.
2. self-assembled composite membrane controlled sustained-release preparation according to claim 1 is characterized in that: described cation type polymer is the chitosan that mean molecule quantity is not less than the different deacetylations of 100kDa.
3. self-assembled composite membrane controlled sustained-release preparation according to claim 1, it is characterized in that: described anionic polymer is the sodium alginate that molecular weight is not less than different mannuronic acids/guluronic acid ratio of 100kDa, molecular weight is not less than the carrageenan of 100kDa, molecular weight be not less than in the sodium carboxymethyl cellulose of 100kDa one of or its compositions.
One of 4. self-assembled composite membrane controlled sustained-release preparation according to claim 1 is characterized in that: described medicine is a theophylline, acetaminophen, and ligustrazine phosphate, aspirin, diclofenac sodium, in the glipizide.
5. self-assembled composite membrane controlled sustained-release preparation according to claim 1 is characterized in that: described other adjuvant is a binding agent, lubricant, solubilizing agents for drugs, one of diluent or its compositions.
6. self-assembled composite membrane controlled sustained-release preparation according to claim 5 is characterized in that: described binding agent is selected from starch, microcrystalline Cellulose, polyvinylpyrrolidone, Polyethylene Glycol, a kind of or its compositions in the ethanol.
7. self-assembled composite membrane controlled sustained-release preparation according to claim 5 is characterized in that: described lubricant is selected from a kind of or its compositions in the following material: magnesium stearate, Pulvis Talci, micropowder silica gel, stearic acid, Polyethylene Glycol.
8. self-assembled composite membrane controlled sustained-release preparation according to claim 5 is characterized in that: described solubilizing agents for drugs is a sodium lauryl sulphate, a kind of or its compositions in the poloxamer; Described diluent is a starch, lactose, sucrose, microcrystalline Cellulose, mannitol, Polyethylene Glycol, a kind of or its compositions in the polyvinylpyrrolidone.
9. the preparation method of a self-assembled composite membrane controlled sustained-release preparation as claimed in claim 1 is characterized in that medicine, cation type polymer, and anionic polymer and other auxiliary materials and mixing, powder directly is pressed into tablet.
10. the preparation method of a self-assembled composite membrane controlled sustained-release preparation as claimed in claim 1, it is characterized in that medicine, cation type polymer, anionic polymer and other auxiliary materials and mixing are granulated, and dry, granulate becomes granule or further is pressed into tablet.
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| CN102274200A (en) * | 2011-08-10 | 2011-12-14 | 深圳致君制药有限公司 | Diclofenac sodium sustained release tablets and preparation process thereof |
| CN102579359A (en) * | 2011-12-29 | 2012-07-18 | 北京科信必成医药科技发展有限公司 | Tamsulosin sustained release pellet and preparation method thereof |
| CN102579358A (en) * | 2011-12-29 | 2012-07-18 | 北京科信必成医药科技发展有限公司 | Drug sustained-release pellet and method for preparing same |
| CN102764261A (en) * | 2012-07-30 | 2012-11-07 | 沈阳药科大学 | Oral composition controlling release of trimetazidine dihydrochloride and preparation method of oral composition |
| CN103442698A (en) * | 2010-12-16 | 2013-12-11 | 细胞基因公司 | Controlled release oral dosage forms of poorly soluble drugs and uses thereof |
| CN115565621A (en) * | 2022-11-29 | 2023-01-03 | 则正(济南)生物科技有限公司 | Internal and external correlation model of theophylline sustained-release tablet, construction method and application |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102133433B (en) * | 2011-03-09 | 2013-12-18 | 中国人民解放军军事医学科学院基础医学研究所 | Injectable cardiac muscular tissue engineering product and preparation method thereof |
| CN102772826B (en) * | 2011-05-12 | 2015-03-25 | 远东新世纪股份有限公司 | Composite particle, its preparation method and composite materials for filling bone defects |
| CN102512512B (en) * | 2011-12-26 | 2014-02-19 | 重庆科技学院 | Preparation method for self-assembly medical composite facial mask |
| CN102579379B (en) * | 2011-12-29 | 2016-08-10 | 北京科信必成医药科技发展有限公司 | A kind of medicament slow release preparation and preparation method thereof |
| CN104497363A (en) * | 2015-01-05 | 2015-04-08 | 中国科学院化学研究所 | Composite material as well as preparation method and application thereof |
| CN106420649A (en) * | 2016-11-21 | 2017-02-22 | 中国药科大学 | Acetaminophen press-coated controlled release tablet based on polyelectrolyte self-assembled film and preparation method of acetaminophen press-coated controlled release tablet |
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2010
- 2010-07-26 CN CN201010245089.XA patent/CN101904818B/en not_active Expired - Fee Related
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| 仲静洁: "门冬氨酸左氧氟沙星缓释片和缓释微丸胶囊的研究", 《中国优秀博硕士学位论文全文数据库 (硕士) 医药卫生科技辑》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103442698A (en) * | 2010-12-16 | 2013-12-11 | 细胞基因公司 | Controlled release oral dosage forms of poorly soluble drugs and uses thereof |
| CN103442698B (en) * | 2010-12-16 | 2016-10-05 | 细胞基因公司 | Controlled release oral dosage form of insoluble drug and application thereof |
| CN102274200A (en) * | 2011-08-10 | 2011-12-14 | 深圳致君制药有限公司 | Diclofenac sodium sustained release tablets and preparation process thereof |
| CN102274200B (en) * | 2011-08-10 | 2013-06-05 | 深圳致君制药有限公司 | Diclofenac sodium sustained release tablets and preparation process thereof |
| CN102579359A (en) * | 2011-12-29 | 2012-07-18 | 北京科信必成医药科技发展有限公司 | Tamsulosin sustained release pellet and preparation method thereof |
| CN102579358A (en) * | 2011-12-29 | 2012-07-18 | 北京科信必成医药科技发展有限公司 | Drug sustained-release pellet and method for preparing same |
| CN102579359B (en) * | 2011-12-29 | 2016-07-06 | 北京科信必成医药科技发展有限公司 | A kind of Tamsulosin sustained release pellet and preparation method thereof |
| CN102579358B (en) * | 2011-12-29 | 2016-08-03 | 北京科信必成医药科技发展有限公司 | A kind of drug sustained-release pellet and preparation method thereof |
| CN102764261A (en) * | 2012-07-30 | 2012-11-07 | 沈阳药科大学 | Oral composition controlling release of trimetazidine dihydrochloride and preparation method of oral composition |
| CN115565621A (en) * | 2022-11-29 | 2023-01-03 | 则正(济南)生物科技有限公司 | Internal and external correlation model of theophylline sustained-release tablet, construction method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101700235A (en) | 2010-05-05 |
| CN101904818B (en) | 2015-03-25 |
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