CN103463637B - Novel sustained-release medicine solid preparation framework material - Google Patents
Novel sustained-release medicine solid preparation framework material Download PDFInfo
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- CN103463637B CN103463637B CN201310379681.2A CN201310379681A CN103463637B CN 103463637 B CN103463637 B CN 103463637B CN 201310379681 A CN201310379681 A CN 201310379681A CN 103463637 B CN103463637 B CN 103463637B
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Abstract
The invention relates to the technical field of pharmaceutical production and provides a novel sustained-release framework material. The material is prepared by mixing crosslinked dextran with other framework materials and is applied to the preparation of a sustained-release solid preparation, so that the sustained-release solid preparation achieves an ideal dissolution effect.
Description
Technical field
The invention belongs to pharmaceutical production technical field, relating to a kind of new sustained-release matrix material for using in pharmaceutical solid preparation production process.
Background technology
At present, domestic and international sustained and controlled release medicament type of preparation is a lot, wherein matrix tablet cost is low, technique simple, it is easy to carry to apply, occupy important share in the market, the key of framework sustained controlling sheet selects suitable framework material, and current framework material mainly comprises single framework material and mixed matrix material two kinds.Single framework material can reach the effect of Drug controlled release to a certain extent, but is difficult to reach steady release; Mixed matrix material combines the advantage of each component material, has both reduced the consumption of framework material, has enhanced safety, solves again the problems such as the not enough and stability of single framework material controlled release is not good.The mixed matrix of the mixed matrix material mainly hypromellose type of existing market application, mainly comprise hydroxypropyl methylcellulose and sodium carboxymethyl cellulose, sodium alginate, octadecanol, compritol 888, polyvinyl alcohol, acrylic resin and polyvinylpyrrolidone etc. used in combination, slow-release solid preparation selects the space selected of framework material smaller, yet there are no cross linked dextran and other framework materials precedent as slow-release solid preparation framework material used in combination both at home and abroad, but cross linked dextran is employed at medical instruments field, its safety visible can be guaranteed, its good water absorption and can be well suited for being applied to the stripping problem solving sustained and controlled release medicament with hydroexpansivity.
Summary of the invention
In order to solve problems of the prior art, the invention provides a kind of new sustained-release matrix material, mix primarily of cross linked dextran and other framework materials, for the preparation of slow-release solid preparation, make slow-release solid preparation reach more preferably result of extraction.
In order to realize object of the present invention, the technical scheme of employing is summarized as follows:
A new pharmaceutical solid preparation sustained-release matrix material, is characterized in that, described framework material is mixed by cross linked dextran and other framework materials.
Described cross linked dextran forms by low molecular dextran is crosslinked.
The preparation were established of described cross linked dextran is: be raw material with low molecular dextran, and add emulsifying agent, cross-linking agent, reverse microemulsion method carries out cross-linking reaction, two-phase laminated flow, extraction, distillation, drying, refining, finally obtains cross linked dextran.
Other framework materials described comprise in hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, sodium alginate, octadecanol, compritol 888, polyvinyl alcohol, acrylic resin and polyvinylpyrrolidone one or several.
The mixed proportion scope of described a kind of new pharmaceutical solid preparation sustained-release matrix material is: cross linked dextran: other framework material=1: 99 ~ 99: 1.
The mixed method of described a kind of new pharmaceutical solid preparation sustained-release matrix material, it is specially: mechanical mixing method mixing, spray drying method mixing, the mixing of congruent melting extrusion molding and wet-dry change are granulated and mixed.
Compared with prior art, the good effect that the present invention has is: because China's preparation technique is delayed for a long time, slow controlled release is less, prepare the hydrophilic and hydrophobic polymer material of sustained-release preparation needs, and the research of China to these macromolecular materials is fewer, main controlled slowly releasing adjuncts dependence on import, thus constrain the development of medicine sustained and controlled release preparation technique, for above-mentioned situation, develop this product, the space selected of sustained-release preparation adjuvant can be enriched, thus improve drug preparation technique, vast medication crowd is benefited.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is described further.
Example 1---the test recipe of mizolastine slow releasing tablet and preparation technology
(1) formula
Principal agent mizolastine 10g
Sustained-release matrix crosslink material Dextran 5 g
Hydroxypropyl methylcellulose (K4M) 6.5g
Acidulant potassium hydrogen tartrate 45g
Diluent lactose 95g
Microcrystalline Cellulose 50g
The ethyl cellulose alcoholic solution of binding agent 10% is appropriate
Magnesium stearate lubricant 1%
Make 1000.
(2) preparation technology
The cross linked dextran of recipe quantity, hydroxypropyl methylcellulose mixer are uniformly mixed 30 minutes, add mizolastine again and continue stirring 30 minutes, after mix homogeneously, add potassium hydrogen tartrate, lactose and microcrystalline Cellulose again and continue mixing 30 minutes to mix homogeneously, cross 80 mesh sieves, add the ethyl cellulose alcoholic solution of appropriate 10%, wet granulation, 20 mesh sieve granulate, add magnesium stearate, tabletting after mix homogeneously.
(3) brief summary
Recording tablet hardness is 10kg, and through In Vitro Dissolution test, the Dissolution of Sustained Release Tablet curve obtained is close with the stripping of external like products, is that sustained-release matrix material has obvious adjustment advantage more separately with hydroxypropyl methylcellulose.
Example 2---the test recipe of ibuprofen slow-release matrix tablet and preparation technology
(1) formula
Principal agent ibuprofen 200g
Sustained-release matrix crosslink material Dextran-20 g
Hydroxypropyl methylcellulose (K100LV) 50g
Diluent lactose 28g
The ethyl cellulose alcoholic solution of binding agent 10% is appropriate
Magnesium stearate lubricant 1.5g
Make 1000.
(2) preparation technology
The cross linked dextran of recipe quantity, hydroxypropyl methylcellulose mix and blend 30 minutes, pre-mixing agent and ibuprofen and lactose are crossed 60 mesh sieves, and mix and blend 30 minutes, mix homogeneously, add the ethyl cellulose alcoholic solution of appropriate 10%, wet granulation, 40 mesh sieve granulate, add magnesium stearate, tabletting after mix homogeneously.
(3) brief summary
Viscosity and the consumption of sustained-release matrix material have a significant effect to release, by the conbined usage of cross linked dextran and hydroxypropyl methylcellulose, select different proportionings, obvious advantage is had to the viscosity and consumption that regulate framework material, easier optimization is suitable for the different formulations of different pharmaceutical, this tests sheet is tested through In Vitro Dissolution, and the Dissolution of Sustained Release Tablet curve obtained is close with the stripping of external like products, is that sustained-release matrix material has obvious adjustment advantage more separately with hydroxypropyl methylcellulose.
The test recipe of example 3---Theo-Dur and preparation technology
(1) prescription
Principal agent theophylline anhydrous 101g
Sustained-release matrix crosslink material dextran 1 .0g
Sodium carboxymethyl cellulose 0.8g
Hydroxypropyl methylcellulose (K100) 1.2g
Diluent lactose 69g
Starch 10g
Binding agent 95% appropriate amount of ethanol
Magnesium stearate lubricant 0.5%
Make 1000.
(2) preparation technology
By the cross linked dextran of recipe quantity, hydroxypropyl methylcellulose mix homogeneously, pre-composition and sodium carboxymethyl cellulose, starch mixer are uniformly mixed 30 minutes, after mix homogeneously, add theophylline anhydrous again, lactose continuation mixing is crossed 80 mesh sieves to mix homogeneously, added appropriate 95% alcoholic solution for 30 minutes, wet granulation, 20 mesh sieve granulate, add magnesium stearate, tabletting after mix homogeneously.
(3) brief summary
Through In Vitro Dissolution test, the Dissolution of Sustained Release Tablet curve obtained is close with the stripping of external like products, by the cooperation of cross linked dextran with other framework materials, for different drug demands, regulates consumption and the viscosity of framework material, demonstrates clear superiority.
The preparation of example 4---cross linked dextran
(1) prepare polysaccharide alkaline solution: claim Dextran 10 g, NaCl 1g, distilled water 30 ~ 100ml, dextran is dissolved in distilled water, regulates pH 8.5 ~ 10.5 with 1mol/L NaOH, stir 2h, mixing speed is 400-600r/min, obtains activating rear dextran alkaline solution;
(2) prepare vegetable oil-dextran mixed solution: after getting surfactant span60 1-3g, vegetable oil 200-1000ml mixing, at 60 ~ 80 DEG C of stirred in water bath 0.5 ~ 2h, then join in step dextran alkali liquor (1), be uniformly mixed 2 ~ 4h, obtain vegetable oil-dextran mixed solution;
(3) crosslinking Treatment: the vegetable oil-dextran mixed solution and dripping cross-linking agent epoxychloropropane 1 ~ 5ml (2) obtained to step, time for adding is 1 ~ 2h, forming reactions system, reaction 4 ~ 6h, temperature 50 C, and mixing speed is 400-600/min;
(4) refine: by step product sucking filtration (3), obtain solid, add 8 ~ 10 times of volume of ethylacetate and stir 4 ~ 8h, mixing speed is 200 ~ 500r/min, sucking filtration; Then 5 ~ 10 times of volume washes of absolute alcohol are added in solids, sucking filtration; Finally use 5 ~ 10 times of volume distilled water washs, lyophilization, obtains pressed powder, obtains product after screening, co-60 radiation sterilizing.
Exemplary scenario described here is only the explanation to the principle of the invention, and preferred embodiment of the present invention, should not by any way, utilizes describing and limit the scope of the invention above.The professional person of this area, can utilize principle of the present invention, designs various different embodiment, and does not exceed scope of the present invention.
Claims (4)
1. a pharmaceutical solid preparation sustained-release matrix material, mixed by cross linked dextran and other framework materials, it is characterized in that, other described framework materials be selected from hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, sodium alginate, octadecanol, compritol 888, polyvinyl alcohol, acrylic resin and polyvinylpyrrolidone one or several; Described cross linked dextran preparation technology is:
1. polysaccharide alkaline solution is prepared: claim Dextran 10 g, NaCl 1g, distilled water 30 ~ 100ml, dextran is dissolved in distilled water, regulates pH 8.5 ~ 10.5 with 1mol/L NaOH, stir 2h, mixing speed is 400-600r/min, obtains activating rear dextran alkaline solution;
2. vegetable oil-dextran mixed solution is prepared: after getting surfactant span60 1-3g, vegetable oil 200-1000ml mixing, at 60 ~ 80 DEG C of stirred in water bath 0.5 ~ 2h, then join in step dextran alkali liquor (1), be uniformly mixed 2 ~ 4h, obtain vegetable oil-dextran mixed solution;
3. crosslinking Treatment: the vegetable oil-dextran mixed solution and dripping cross-linking agent epoxychloropropane 1 ~ 5ml (2) obtained to step, time for adding is 1 ~ 2h, forming reactions system, reaction 4 ~ 6h, temperature 50 C, and mixing speed is 400-600/min;
4. refine: by step product sucking filtration 3., obtain solid, add 8 ~ 10 times of volume of ethylacetate and stir 4 ~ 8h, mixing speed is 200 ~ 500r/min, sucking filtration; Then 5 ~ 10 times of volume washes of absolute alcohol are added in solids, sucking filtration; Finally use 5 ~ 10 times of volume distilled water washs, lyophilization, obtains pressed powder, obtains product after screening, co-60 radiation sterilizing.
2. a kind of pharmaceutical solid preparation sustained-release matrix material as claimed in claim 1, is characterized in that, described cross linked dextran forms by low molecular dextran is crosslinked.
3. a kind of pharmaceutical solid preparation sustained-release matrix material as claimed in claim 1, it is characterized in that, mixed proportion scope is: cross linked dextran: other framework material=1: 99 ~ 99: 1.
4. a kind of pharmaceutical solid preparation sustained-release matrix material as claimed in claim 1, it is characterized in that, mixed method is specially: mechanical mixing method mixing, spray drying method mixing, the mixing of congruent melting extrusion molding and wet-dry change are granulated and mixed.
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| CN1067281C (en) * | 1997-05-22 | 2001-06-20 | 吴湘君 | Cohesive and hydrophilic gel for medical use, and method for preparing same |
| WO2013039993A1 (en) * | 2011-09-14 | 2013-03-21 | Royer Biomedical, Inc. | Bioresorbable drug delivery matrices based on cross-linked polysaccharides, dosage forms designed for delayed/controlled release |
| CN102603417A (en) * | 2012-03-31 | 2012-07-25 | 山东喜丰田生态肥业有限公司 | Xyloglucan enveloped water-retention slow release fertilizer |
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