CN101254180A - Nimodipine capsule containing semi-solid combination and preparation - Google Patents
Nimodipine capsule containing semi-solid combination and preparation Download PDFInfo
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- CN101254180A CN101254180A CNA2008100107728A CN200810010772A CN101254180A CN 101254180 A CN101254180 A CN 101254180A CN A2008100107728 A CNA2008100107728 A CN A2008100107728A CN 200810010772 A CN200810010772 A CN 200810010772A CN 101254180 A CN101254180 A CN 101254180A
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Abstract
The invention discloses a nimodipine capsule with high dissolution and semi-solid composition as content and a preparation method thereof, and belongs to the pharmaceutical preparation field. The method comprises the following steps of mixing micronized nimodipine and a hydrophilic carrier, preparing into solid dispersion by melting extrusion method, cooling, pulverizing, mixing with semi-solid matrix, surfactant, melting point regulator under heating, and filling the content into hard capsule with a capsule filling machine. The invention combines the melting extrusion technique and semi-solid filling hard capsule technique, and after the prepared novel nimodipine capsule is administered into human body, the nimodipine quickly diffuses in molecular form and saturates metabolic enzymes, so as to improve bioavailability. The inventive nimodipine capsule solves the low dissolution and low utilization ratio problems of prior nimodipine preparation; and has the advantages of high dissolution, good stability, simple preparation method, and applicability to industrial production.
Description
Technical field:
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of content and be semi-solid combination, high-dissolution nimodipine capsules agent and preparation method thereof.
Background technology:
The dissolution that utilizes solid dispersions technique to improve poorly water soluble drugs is an a kind of relative effective method commonly used in recent years.Solid dispersion is meant that medicine is dispersed in formed dispersion in a certain solid-state carrier material with states such as molecule, colloidal state, amorphous, crystallites.Its mechanism of release is that the dissolution rate of medicine and its specific surface area are closely related, and promptly unit volume medicine specific surface area is big more, and dissolution is high more, and carrier itself has facilitation to the stripping of medicine in addition.In recent years, be the starting point with the convenience of suitability for industrialized production solid dispersion, extrusion by melting prepares solid dispersion to be developed gradually.Material is delivered into one piecemeal in the machine barrel of temperature control with the frequency of setting, and be preheated, material in the machine barrel is extruded, under the promotion of screw rod medial surface counteracting force and machine tube inner wall frictional force, move forward, in four zones, apply the multistep unit operations continuously, by the cutting peptizaiton of shearing elements and the shunting of hybrid element, configuration and immixture, add the heat energy of machine barrel heating watt and the two-axis extruder tool energy of screw rod, making material is molecular state by aggregation state change, realize the refinement of material of the same race and the homogenize of xenogenesis storeroom, finally reach the uniform mixing of molecular state.But for most of medicine, after making solid dispersion,, face long-time placement again because there is the particularity of form in medicine, temperature or humidity make the medicine molecular aggregates become nucleus, metastable-state crystal to be converted into stable type improperly, so that the problem of dissolution reduction.Therefore, delaying solid dispersion aging is another difficult problem in the commercial production.
The seventies in 20th century, abroad begin one's study liquid or semi-solid fill hard capsule technology, and obtained development faster.Its technical characterstic is under the high temperature liquid state or semi-solid content to be filled into hard capsule, and dosage was accurate when good flowability had guaranteed to load; Preparation is at room temperature fastened for semisolid, solid or capsule, is easy to preserve and transportation; Do not need binding agent, lubricant, fluidizer in the preparation process, avoid dust from flying, prevent the air oxidation of medicine chance, and technology is simple, with low cost.This technology is widely used in improving the insoluble drug oral administration biaavailability, low melting point substance is made the preparation of oral solid formulation, assurance low dosage or potent content of medicines uniformity, hygroscopicity medicine processing, sustained and controlled release medicament etc. in recent years.
Nimodipine is a dihydropyridine calcium ion antagonist, can selectively acting in calcium channel, specifically with the reversible combination of relevant receptor, regulate calcium ion concentration in the vascular smooth muscle, cause smooth muscle loosening, reverse vasospasm, improve blood supply.Because nimodipine is a fat-soluble medicine, can pass through blood brain barrier, therefore can protect brain cell, improve it to anoxybiotic toleration.Clinical practice at present is in disordered brain functioies such as treatment ischemic cerebrovascular, migraine, cerebral infarction, cerebral hemorrhage, light, moderate hypertension, senile dementia, diseases such as vertebra 2 basilar artery insufficiencies.
Nimodipine is fat-soluble medicine (LogP=3.855), dissolubility minimum (about 4 μ g/ml) in the water, enter gastrointestinal tract after, its hydrophobicity makes it to be easy to assemble, and is difficult to realize transmembrane transport, curative effect can't be brought into play, oral administration biaavailability is not high.So, improve its dissolution and become the crucial part that improves the said preparation biological utilisation.Bibliographical information is not arranged for the nimodipine capsules agent of nimodipine capsules agent that can prepare semi-solid medicament and semi-solid medicament and Nimodipine solid dispersant can improving aspect the high-dissolution so far.
Summary of the invention:
Goal of the invention: the invention provides a kind of content is high-dissolution nimodipine capsules agent of semi-solid combination and preparation method thereof, it is low and existing Nimodipine solid dispersoid is easily aging that its purpose is to solve in the past the nimodipine medicament dissolution, the problem that causes aspect such as dissolution reduction to exist.
Technical scheme: the present invention is achieved through the following technical solutions:
A kind of content is the nimodipine capsules agent of semi-solid combination, capsule material by content and contents of parcel thing is formed, it is characterized in that: this content is a semi-solid state, and its component mainly is made up of Nimodipine solid dispersoid, semisolid matrix, surfactant; The content of Nimodipine solid dispersoid wherein accounts for the 2.5-35% of content weight percentage ratio, and the content of semisolid matrix accounts for the 35.5-92.5% of content weight percentage ratio, and the content of surfactant accounts for the 5-30% of content weight percentage ratio.
Content in this capsule also includes the fusing point regulator, and the content of fusing point regulator accounts for the 0-2.5% of content weight percentage ratio.
Nimodipine solid dispersoid is prepared with extrusion by melting by nimodipine and hydrophilic carrier; Nimodipine and hydrophilic carrier are 1: 0.5～20 with weight ratio.
Described hydrophilic carrier is one or more among Polyethylene Glycol, polyvinylpyrrolidone, copolyvidone, hypromellose, poloxamer, No. 4, acrylic resin, the strange E100 of You Te and the strange EPO of You Te.
Described semisolid matrix is one or more in Polyethylene Glycol, glycerol, polyvidone, copolyvidone, Myrj 45, polyethylene glycol fatty acid glyceride, polyoxyethylene castor oil, the polyoxyethylene hydrogenated Oleum Ricini.
Described surfactant is one or more in anhydro sorbitol fatty acid ester, polyethenoxy sorbitan fatty acid ester, the poloxamer.
Described fusing point regulator is a Polyethylene Glycol.
The preparation method of the nimodipine capsules agent that a kind of aforesaid content is a semi-solid combination is characterized in that: this preparation method is carried out according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: is 1: 0.5～20 to carry out premixing by micronized nimodipine and hydrophilic carrier with weight ratio, add single screw rod or twin screw and melt extrude machine, the temperature of each section is not higher than 200 ℃, melt extrude being lower than under 100 rev/mins the rotating speed, obtain faint yellow again after the quenching to golden transparent or translucent solid dispersion; Refrigerative solid dispersion is pulverized, sieved, making particle diameter is the 40-200 order, promptly gets Nimodipine solid dispersoid;
B. the preparation of nimodipine capsules agent: with percentage by weight is that the semisolid matrix of 35.5-92.5%, the surfactant that percentage by weight is 5-30% mix, 40-200 ℃ of heated and stirred, evenly adding percentage by weight in back is the Nimodipine solid dispersoid powder of 2.5-35%, continue heated and stirred to even, when treating that system temperature is reduced to 45-100 ℃, form the content of semi-solid state, with liquid-filling capsule filling machine quantitatively content is packed into gelatine capsule or cellulose capsule, wherein, every capsules contains nimodipine 10-30mg.
The fusing point regulator that also with percentage by weight is 0-2.5% in step b mixes with semisolid matrix, surfactant.
Advantage and effect: the invention provides a kind of content is high-dissolution nimodipine capsules agent of semi-solid combination and preparation method thereof, this method is at first made nimodipine the Nimodipine solid dispersant, use liquid or semi-solid fill hard capsule technology that Nimodipine solid dispersoid, semisolid matrix, surfactant, fusing point regulator are prepared into capsule again, the fusing point regulator in this component has the effect of suspending agent concurrently; This capsule has changed the dosage form of former nimodipine capsules agent; The capsule of this method preparation has solved also that Nimodipine solid dispersoid is easily aging in the past when having improved the nimodipine dissolution greatly, influence the problem of dissolution, is convenient to transport and deposit; This preparation method is simple, is easy to suitability for industrialized production; The novel nimodipine capsules dissolution rate of preparation is fast; In medicine enters body, be converted into liquid for semisolid content under the room temperature, after softgel shell breaks, the content that has been converted into liquid state scatter immediately, the molecular state nimodipine spreads rapidly with adjuvant, its specific surface area infinitely increases in limited space, and dissolution significantly increases, and metabolic enzyme is by saturated rapidly, high amount of drug is absorbed in short time, can weaken first pass effect to a certain extent, improve bioavailability; This nimodipine capsules agent is placed for a long time by commercially available back, still has than high-dissolution.
Description of drawings
Fig. 1 is the dissolution comparison diagram of the various dosage forms of nimodipine in 900mL 0.1MHCl;
Fig. 2 is 75 ± 5% for temperature at 40 ± 2 ℃, humidity, at 900mL 0.1MHCl, the comparison diagram of Nimodipine solid dispersant and dissolution of the present invention in 30 minutes the solution (press commercially available back in 1,2,3,4,, 5,6 months dissolution);
Fig. 3 is 60 ± 10% for temperature at 25 ± 2 ℃, humidity, at 900mL 0.1MHCl, and the comparison diagram of Nimodipine solid dispersant and dissolution of the present invention in 30 minutes the solution (pressing commercially available back) in 3,6,9,12 months dissolution.
The specific embodiment:
The present invention will be further described below in conjunction with accompanying drawing:
Embodiment 1: prepare the nimodipine capsules agent according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: with copolyvidone S630 and the strange E100 of You Te is carrier, get 3 parts of micronization nimodipine, 5 parts of strange E100 of You Te and 2 parts of copolyvidone S630 (by weight), behind the uniform mixing, add the loading hopper that twin screw melt extrudes machine, it is 115 ℃ that district's temperature is set, two, three, four district's temperature are 130 ℃, revolution is 36 rev/mins, extrudate is put quenching in (70) ℃ refrigerator, pulverizes, cross 120 mesh sieves, promptly get Nimodipine solid dispersoid.
B. the preparation of nimodipine capsules agent: get semisolid matrix copolyvidone S630/72g, polyethenoxy sorbitan fatty acid ester (Tween 80)/96g, semisolid matrix PEG400/360g, polyethylene glycol 6000/8.4g, 90 ℃ of heated and stirred evenly add Nimodipine solid dispersoid powder/120g in the back, continue to be stirred to evenly, be cooled to 60 ℃, with the liquid-filling capsule filling machine cellulose capsule of quantitatively content being packed into, its content is a semi-solid state, every capsules contains the about 550mg of content, wherein contains nimodipine 30mg.
Polyethylene Glycol is as the fusing point regulator, has the effect of suspending agent simultaneously again, and the homodisperse of effective ingredient in the medicine is played important effect.
Embodiment 2: prepare the nimodipine capsules agent according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: with copolyvidone S630 is carrier, get 2 parts of micronization nimodipine and 8 parts of copolyvidone S630 (by weight), behind the uniform mixing, add the loading hopper that twin screw melt extrudes machine, it is 115 ℃ that district's temperature is set, two, three, four district's temperature are 125 ℃, revolution is 30 rev/mins, extrudate is put quenching in (30) ℃ refrigerator, pulverizes, cross 100 mesh sieves, promptly get Nimodipine solid dispersoid.
B. the preparation of nimodipine capsules agent: get anhydro sorbitol fatty acid ester (sorbester p18)/120g, semisolid matrix PEG400/300g, glycerol/72g, Polyethylene Glycol 8000/12g, 80 ℃ of heated and stirred evenly add Nimodipine solid dispersoid powder/120g in the back, continue to be stirred to evenly, be cooled to 60 ℃, with the liquid-filling capsule filling machine cellulose capsule of quantitatively content being packed into, every capsules contains the about 520mg of content, wherein contains nimodipine 20mg.
Embodiment 3: prepare the nimodipine capsules agent according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: with acrylic resin is for No. 4 carrier, get 3 parts of micronization nimodipine, 7 parts of No. 4, acrylic resins (by weight), behind the uniform mixing, add the loading hopper that single screw rod melt extrudes machine, it is 105 ℃ that district's temperature is set, two, three, four district's temperature are 135 ℃, revolution is 24 rev/mins, and extrudate is put the room temperature cooling, pulverizes, cross 100 mesh sieves, promptly get Nimodipine solid dispersoid.
B. the preparation of nimodipine capsules agent: get poloxamer 188/120g, glycerol 300g, 75 ℃ of heated and stirred evenly add Nimodipine solid dispersoid powder/120g in the back, continue to be stirred to evenly, be cooled to 70 ℃, with the liquid-filling capsule filling machine cellulose capsule of quantitatively content being packed into, every capsules contains the about 450mg of content, wherein contains nimodipine 30mg.
Embodiment 4: prepare the nimodipine capsules agent according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: with the hypromellose is carrier, get 1 part of micronization nimodipine, 9 parts of hypromelloses, behind the uniform mixing, add the loading hopper that twin screw melt extrudes machine, it is 100 ℃ that district's temperature is set, two, three, four district's temperature are 130 ℃, revolution is 30 rev/mins, and extrudate is put the room temperature cooling, pulverizes, cross 80 mesh sieves, promptly get Nimodipine solid dispersoid.
B. the preparation of nimodipine capsules agent: taking polyethylene glycol fatty glyceride (Gelucire44/14)/120g, poloxamer 188/72g, glycerol/240g, Polyethylene Glycol 8000/12g, 85 ℃ of heated and stirred evenly add Nimodipine solid dispersoid powder/120g in the back, continue to be stirred to evenly, be cooled to 65 ℃, with the liquid-filling capsule filling machine cellulose capsule of quantitatively content being packed into, every capsules contains the about 470mg of content.
Embodiment 5: prepare the nimodipine capsules agent according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: with the Polyethylene Glycol is carrier, get 1 part of micronization nimodipine, 9 parts of Polyethylene Glycol, behind the uniform mixing, add the loading hopper that twin screw melt extrudes machine, it is 100 ℃ that district's temperature is set, two, three, four district's temperature are 130 ℃, revolution is 30 rev/mins, and extrudate is put the room temperature cooling, pulverizes, cross 80 mesh sieves, promptly get Nimodipine solid dispersoid.
B. the preparation of nimodipine capsules agent: get polyvidone 120g, poloxamer 188/72g, polyoxyethylene (40) stearate 240g, 85 ℃ of heated and stirred evenly add Nimodipine solid dispersoid powder/120g in the back, continue to be stirred to evenly, be cooled to 65 ℃, with the liquid-filling capsule filling machine cellulose capsule of quantitatively content being packed into, every capsules contains the about 470mg of content.
Present embodiment does not have the fusing point regulator, and also can prepare content is the nimodipine capsules agent of semi-solid combination, and just effective ingredient is difficult for homodisperse in the medicine.
Embodiment 6: prepare the nimodipine capsules agent according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: with the poloxamer is carrier, get 3 parts of micronization nimodipine, 7 parts of poloxamers, behind the uniform mixing, add the loading hopper that twin screw melt extrudes machine, it is 105 ℃ that district's temperature is set, two, three, four district's temperature are 135 ℃, revolution is 24 rev/mins, and extrudate is put the room temperature cooling, pulverizes, cross 100 mesh sieves, promptly get Nimodipine solid dispersoid.
B. the preparation of nimodipine capsules agent: get poloxamer 188/120g, polyoxyethylene castor oil 300g, 75 ℃ of heated and stirred evenly add Nimodipine solid dispersoid powder/120g in the back, continue to be stirred to evenly, be cooled to 70 ℃, with the liquid-filling capsule filling machine cellulose capsule of quantitatively content being packed into, every capsules contains the about 450mg of content.
Embodiment 7: prepare the nimodipine capsules agent according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: with the polyvinylpyrrolidone is carrier, get 2 parts of micronization nimodipine and 8 parts of polyvinylpyrrolidones, behind the uniform mixing, add the loading hopper that twin screw melt extrudes machine, it is 115 ℃ that district's temperature is set, two, three, four district's temperature are 125 ℃, revolution is 30 rev/mins, extrudate is put quenching in (20) ℃ refrigerator, pulverizes, cross 100 mesh sieves, promptly get Nimodipine solid dispersoid.
B. the preparation of nimodipine capsules agent: get sorbester p18/120g, PEG400/300g, polyoxyethylene (40) castor oil hydrogenated 72g, Polyethylene Glycol 8000/12g, 80 ℃ of heated and stirred evenly add Nimodipine solid dispersoid powder/120g in the back, continue to be stirred to evenly, be cooled to 60 ℃, with the liquid-filling capsule filling machine cellulose capsule of quantitatively content being packed into, every capsules contains the about 520mg of content, wherein contains nimodipine 20mg.
Embodiment 8: prepare the nimodipine capsules agent according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: with copolyvidone S630 and the strange EPO of You Te is carrier, get 3 parts of micronization nimodipine, 5 parts of strange EPO of You Te and 2 parts of copolyvidone S630, behind the uniform mixing, add the loading hopper that twin screw melt extrudes machine, it is 115 ℃ that district's temperature is set, two, three, four district's temperature are 130 ℃, revolution is 36 rev/mins, extrudate is put quenching in (70) ℃ refrigerator, pulverizes, cross 120 mesh sieves, promptly get Nimodipine solid dispersoid.
B. the preparation of nimodipine capsules agent: get copolyvidone S630/72g, Tween 80/96g, PEG400/360g, polyethylene glycol 6000/8.4g, 90 ℃ of heated and stirred evenly add Nimodipine solid dispersoid powder/120g in the back, continue to be stirred to evenly, be cooled to 60 ℃, with the liquid-filling capsule filling machine cellulose capsule of quantitatively content being packed into, every capsules contains the about 550mg of content, wherein contains nimodipine 30mg.
Is that the preparation method of the high-dissolution nimodipine capsules agent of semi-solid combination compares below in conjunction with common preparation method and accompanying drawing to this content:
Among Fig. 1,2,3: " ◇ " symbol is commercially available homemade nimodipine tablet; " ● " symbol is commercially available homemade nimodipine capsules; " zero " symbol is commercially available import nimodipine tablet; " ■ " symbol is the nimodipine capsules of embodiment 1 preparation; " " symbol is the solid dispersion physical mixture of comparative example 1 preparation; " ▲ " symbol is the Nimodipine solid dispersoid powder of comparative example 2; " ◆ " symbol is the nimodipine capsules of comparative example 3; "-" symbol is a nimodipine micronization crude drug.
Comparative example 1:
Get 3 parts of micronization nimodipine, 5 parts of strange E100 of You Te and 2 parts of copolyvidone S630, uniform mixing, the preparation physical mixture quantitatively incapsulates, and every capsules contains nimodipine 30mg.
Comparative example 2:
Nimodipine solid dispersoid powder among the embodiment 1 quantitatively incapsulates, and every capsules contains nimodipine 30mg.
Comparative example 3:
Use the nimodipine crude drug directly to prepare capsule.Preparation method with reference to capsule among the embodiment 1 is changed slightly, get copolyvidone S630/72g, Tween 80/96g, PEG400/360g, polyethylene glycol 6000/7.2g, 90 ℃ of heated and stirred evenly add micronization nimodipine/36g in the back, continue to be stirred to evenly, be cooled to 60 ℃, with the liquid-filling capsule filling machine cellulose capsule of quantitatively content being packed into, every capsules contains the about 480mg of content, wherein contains nimodipine 30mg.
Dissolution determination
For simulated in vivo environment more truly, do not add solubilizing agent, cosolvents such as surfactant, ethanol in the dissolution medium.With the 900mL0.1M hydrochloric acid solution through the degassing is dissolution medium, adopt the slurry method, 75 rev/mins, keep 37 ± 0.5 ℃, respectively at sampling in 10,20,30,45,60 minutes, 0.45 μ m filtering with microporous membrane discarded subsequent filtrate, ultraviolet visible spectrophotometry working sample trap, the detection wavelength is 355nm.Calculate dissolution, dissolution was certified products greater than 80% in 30 minutes.
Working sample is the nimodipine capsules of commercially available homemade nimodipine tablet, commercially available homemade nimodipine capsules, commercially available import nimodipine tablet, embodiment 1 preparation, the solid dispersion physical mixture of comparative example 1 preparation, the Nimodipine solid dispersoid powder of comparative example 2, the nimodipine capsules of comparative example 3.
Show according to accompanying drawing 1,2,3 and correlated dissolution result: the dissolution of Nimodipine solid dispersoid all is significantly increased than micronization crude drug and physical mixture, utilize semi-solid content to load these post processing means of hard capsule, can obtain the even more ideal nimodipine preparation of dissolution; Nimodipine directly mixes with semisolid matrix, surfactant, fusing point regulator, also can obtain the nimodipine capsules of high-dissolution, but stability test shows: press commercially available back, placed 6 months under 40 ± 2 ℃, humidity 75 ± 5% conditions, 25 ± 2 ℃, humidity are to place 12 months under 60 ± 10% conditions, the content that contains solid dispersion of the present invention is that semisolid nimodipine capsules dissolution can keep being not less than 90%, and the capsule dissolution that solid dispersion powder and crude drug directly prepare all has obvious reduction.
For poorly water soluble drugs, the semi-solid post processing means of loading the hard capsule technology as a kind of solid dispersion can make high-dissolution and the still more stable nimodipine quick releasing formulation of long-term placement.
Claims (9)
1, a kind of content is the nimodipine capsules agent of semi-solid combination, capsule material by content and contents of parcel thing is formed, it is characterized in that: this content is a semi-solid state, and its component mainly is made up of Nimodipine solid dispersoid, semisolid matrix, surfactant; The content of Nimodipine solid dispersoid wherein accounts for the 2.5-35% of content weight percentage ratio, and the content of semisolid matrix accounts for the 35.5-92.5% of content weight percentage ratio, and the content of surfactant accounts for the 5-30% of content weight percentage ratio.
2, a kind of content according to claim 1 nimodipine capsules agent that is semi-solid combination, it is characterized in that: the content in this capsule also includes the fusing point regulator, and the content of fusing point regulator accounts for the 0-2.5% of content weight percentage ratio.
3, a kind of content according to claim 1 nimodipine capsules agent that is semi-solid combination, it is characterized in that: Nimodipine solid dispersoid is prepared with extrusion by melting by nimodipine and hydrophilic carrier; Nimodipine and hydrophilic carrier are 1: 0.5～20 with weight ratio.
4, a kind of content according to claim 3 nimodipine capsules agent that is semi-solid combination, it is characterized in that: described hydrophilic carrier is one or more among Polyethylene Glycol, polyvinylpyrrolidone, copolyvidone, hypromellose, poloxamer, No. 4, acrylic resin, the strange E100 of You Te and the strange EPO of You Te.
5, a kind of content according to claim 1 nimodipine capsules agent that is semi-solid combination, it is characterized in that: described semisolid matrix is one or more in Polyethylene Glycol, glycerol, polyvidone, copolyvidone, Myrj 45, polyethylene glycol fatty acid glyceride, polyoxyethylene castor oil, the polyoxyethylene hydrogenated Oleum Ricini.
6, a kind of content according to claim 1 nimodipine capsules agent that is semi-solid combination, it is characterized in that: described surfactant is one or more in anhydro sorbitol fatty acid ester, polyethenoxy sorbitan fatty acid ester, the poloxamer.
7, a kind of content according to claim 1 nimodipine capsules agent that is semi-solid combination, it is characterized in that: described fusing point regulator is a Polyethylene Glycol.
8, the preparation method of a kind of content as claimed in claim 1 nimodipine capsules agent that is semi-solid combination, it is characterized in that: this preparation method is carried out according to the following steps:
A. Preparation of Nimodipine Solid Dispersion: is 1: 0.5～20 to carry out premixing by micronized nimodipine and hydrophilic carrier with weight ratio, add single screw rod or twin screw and melt extrude machine, the temperature of each section is not higher than 200 ℃, melt extrude being lower than under 100 rev/mins the rotating speed, obtain faint yellow again after the quenching to golden transparent or translucent solid dispersion; Refrigerative solid dispersion is pulverized, sieved, making particle diameter is the 40-200 order, promptly gets Nimodipine solid dispersoid;
B. the preparation of nimodipine capsules agent: with percentage by weight is that the semisolid matrix of 35.5-92.5%, the surfactant that percentage by weight is 5-30% mix, 40-200 ℃ of heated and stirred, evenly adding percentage by weight in back is the Nimodipine solid dispersoid powder of 2.5-35%, continue heated and stirred to even, when treating that system temperature is reduced to 45-100 ℃, form the content of semi-solid state, with liquid-filling capsule filling machine quantitatively content is packed into gelatine capsule or cellulose capsule, wherein, every capsules contains nimodipine 10-30mg.
9, the preparation method of a kind of content according to claim 8 nimodipine capsules agent that is semi-solid combination, it is characterized in that: the fusing point regulator that also with percentage by weight is 0-2.5% in step b mixes with semisolid matrix, surfactant.
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| CN101474177A (en) * | 2008-11-26 | 2009-07-08 | 沈阳药科大学 | Nimodipine solid dispersoid and preparation method thereof |
| CN101836981B (en) * | 2009-12-01 | 2011-12-14 | 严洁 | Compound valsartan benzenesulfonic acid amlodipine medicament composition and new preparation method thereof |
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| CN101474177A (en) * | 2008-11-26 | 2009-07-08 | 沈阳药科大学 | Nimodipine solid dispersoid and preparation method thereof |
| CN101474177B (en) * | 2008-11-26 | 2014-07-23 | 沈阳药科大学 | Nimodipine solid dispersoid and preparation method thereof |
| CN101836981B (en) * | 2009-12-01 | 2011-12-14 | 严洁 | Compound valsartan benzenesulfonic acid amlodipine medicament composition and new preparation method thereof |
| CN102946871A (en) * | 2010-06-04 | 2013-02-27 | 埃斯蒂文博士实验室股份有限公司 | Pharmaceutical compositions of co-crystals of tramadol and coxibs |
| CN103006536A (en) * | 2011-09-26 | 2013-04-03 | 沈阳药科大学 | Preparation method of nimodipine solid dispersible medicament by supercritical fluid technology |
| CN103169676A (en) * | 2011-12-23 | 2013-06-26 | 石药集团中奇制药技术（石家庄）有限公司 | Butylphthalide sublingual tablet and preparation method thereof |
| CN103169676B (en) * | 2011-12-23 | 2016-12-14 | 石药集团中奇制药技术（石家庄）有限公司 | A kind of butylphthalide sublingual tablet and preparation method thereof |
| CN105287427A (en) * | 2015-10-20 | 2016-02-03 | 沈阳红旗制药有限公司 | Semi-solid rifampicin capsule and preparation method thereof |
| CN111405894A (en) * | 2017-11-30 | 2020-07-10 | 比特制药股份有限公司 | Method and apparatus for preparing solid dispersion |
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