CN100413490C - Insoluble medicine transdemal absorption preparation and process for preparing same - Google Patents
Insoluble medicine transdemal absorption preparation and process for preparing same Download PDFInfo
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- CN100413490C CN100413490C CNB031116574A CN03111657A CN100413490C CN 100413490 C CN100413490 C CN 100413490C CN B031116574 A CNB031116574 A CN B031116574A CN 03111657 A CN03111657 A CN 03111657A CN 100413490 C CN100413490 C CN 100413490C
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Abstract
The present invention relates to an indissoluble medicine transdemal absorption preparation and a preparing method thereof. The present invention enhances the solubility of indissoluble medicines in transdemal absorption preparations and increases permeation rate for enhancing the bioavailability of skin absorption. The indissoluble medicine transdemal absorption preparation comprises the following components: 2 to 10 percents by weight of medicine comprising microemulsion, 4 to 6 percents by weight of high molecular polymers, 0.1 to 0.4 percent by weight of cross-linking agents, 0.1 to 0.5 of percent by weight of organic acid, 5 to 40 percents by weight of humectant, 30 to 50 percents by weight of distilled water and 3 to 5 percents by weight of penetration accelerants. In the method, firstly, a microemulsion preparation is prepared; afterwards, adhesive substrates are prepared, are added with the medicine comprising microemulsion by stirring and are finally added with the penetration accelerants. The present invention has no irritation to skin and enhances the compliance of patients, and the preparation comprises no organic solvent for reducing safety hidden dangers in large production.
Description
Technical field:
The present invention relates to medical technical field, particularly pastille microemulsion water base matter patch---insoluble drug transdermal absorption formulation and the preparation technology thereof who absorbs through human body skin.
Background technology:
In recent years, the hot subject of transdermal absorption formulation research having become pharmaceutical field, this kind preparation has the unrivaled advantage of other preparations: 1, can avoid the first pass effect and the gastrointestinal tract degraded of liver, make medicine directly enter blood of human body circulation performance drug effect, the absorption of medicine is not influenced by gastrointestinal factors, has reduced the individual variation of medication.2, can produce constant, controlled blood drug level, avoid the peak valley phenomenon of the blood drug level that oral administration etc. causes, keep blood level to be stabilized in effective treatment concentration range, thereby reduce toxicity.3, after the administration of many medicine oral administration, because the first pass effect bioavailability is lower, T
1/2Short, need frequent drug administration several times on the one, for the very inconvenience of patient of long-term medication, and transdermal patch only need be affixed on behind the ear or the front once a day, and administration is very convenient, is easily accepted by the patient, has improved compliance of patients.4, have why not suitablely as the patient, can interrupt at any time or resume treatment.In view of above advantage, medicine is made transdermal absorption formulation, the medicine more serious to first pass effect, especially the prefered method really for the medicine that needs are taken for a long time, but present studies show that, for water soluble drug, no matter be to consider or take all factors into consideration from the aspects such as control of suitability for industrialized production from the angle of preparation method, the difficulty that is made into transdermal absorption formulation is little more a lot of than insoluble drug.If insoluble drug is made transdermal absorption formulation, how to overcome the aqueous skin corium promptly becomes problem to the barrier action of insoluble drug emphasis.Insoluble drug generally has higher fat-soluble, than the easier horny layer that penetrates of water soluble drug, and directly arrives skin corium, and huge capillary network can absorb the drug very soon into blood under the skin corium, thereby reaches drug effect.But practical experience according to the inventor, insoluble drug is because dissolubility is very low, content in preparation is lower, thereby be difficult to form higher Concentraton gradient in the skin both sides, the diffusion and the infiltration of medicine have finally been limited, nor enter the skin corium of aqueous easily, so be difficult to reach effective therapeutic dose in the body, this point has seriously restricted the research of insoluble drug transdermal absorption formulation.
Japan publication A 61K 9,/70 341 discloses a kind of method of vinpocetine being made transdermal absorption formulation, the binder that this method relates generally to is the acrylic resin base polymer, with an organic solvent as solvent, medicine is dispersed in the acrylic resin viscose glue, forms the matrix-type transdermal absorbable preparation.Because the dissolubility of vinpocetine is very little, the drug loading of this kind preparation is less relatively, be affixed on the skin after, be difficult to the Concentraton gradient that reaches higher, thereby limited the percutaneous absorption rate of medicine; In addition,, in preparation process, can cause organic solvent residue, may cause zest skin because this kind preparation used organic solvent, and in big commercial production if with an organic solvent, will inevitably cause potential danger.
The inventor is when addressing this problem, adopted new medicinal preparation---microemulsion formulation, because the existence of surfactant, cosurfactant, formed very low interfacial tension at oil-water interfaces, even negative value, make the microemulsion particle can reach 10～100nm, and from its preparation technology, the formation of microemulsion is spontaneous, hardly need be by mechanical external force, or only need very little external force.After being wrapped in insoluble drug wherein, dissolubility can increase up to a hundred or thousands of times, and thermodynamic activity improves greatly, can reduce cuticular barrier action, and enter skin corium easily, thereby solved the problem that drug loading is little, difficulty is permeated behind the preparation capable of permeating skin that is made into.After its substrate with the aqueous patch being mixed, effect that can percutaneous aquation further increases the transdermal amount again, thereby improves bioavailability in the body.This patch does not have zest owing to contain a large amount of moisture and wetting agent to skin, has improved patient's compliance, owing to do not contain inflammable and explosive organic solvent in the preparation, has significantly reduced the security hidden trouble in the big production.
Summary of the invention:
The invention provides a kind of insoluble drug transdermal absorption formulation and preparation technology thereof, with insoluble drug---vincamine and methyl ester thereof, ethyl ester; Nitrendipine, nicardipine, nisoldipine, nimodipine and their hydrochlorate are made the method for transdermal absorption formulation, the problem that solves is the dissolubility that increases insoluble drug, further improve the bioavailability after insoluble drug absorbs by human body skin, and the zest of avoiding preparation that skin is caused to greatest extent, adopt microemulsion formulation described in the technical background and aqueous patch for this reason.
Water-based patch of the present invention comprises pastille microemulsion 2～10 weight portions, high molecular polymer 4～6 weight portions, cross-linking agent 0.1～0.4 weight portion, organic acid 0.1～0.5 weight portion, wetting agent 5～40 weight portions, distilled water 30～50 weight portions, penetration enhancer 3～5 weight portions.Optimized technical scheme is pastille microemulsion 2～5 weight portions, high molecular polymer 4～5 weight portions, cross-linking agent 0.2～0.4 weight portion, organic acid 0.2～0.4 weight portion, wetting agent 15～40 weight portions, distilled water 40～50 weight portions, penetration enhancer 4～5 weight portions.
Described pastille microemulsion formulation contains following composition: insoluble drug 0.05～10 weight portion, oil phase 1～10 weight portion, surfactant 10～40 weight portions, cosurfactant 5～30 weight portions, aqueous favoring 50～80 weight portions.Optimized technical scheme is insoluble drug 1～10 weight portion, oil phase 1～8 weight portion, surfactant 15～40 weight portions, cosurfactant 10～30 weight portions, aqueous favoring 60～80 weight portions.
Described insoluble drug has vincamine and methyl ester thereof, ethyl ester, and vincamine is the alkaloid that extracts in the little graceful Herba Catharanthi Rosei, and it is made methyl ester and ethyl ester respectively, obtains apo-Changchun amino acid methyl ester and Apovincaminic Acid Ethyl Ester (vinpocetine); Nitrendipine, nicardipine, nisoldipine, nimodipine and their hydrochlorate have similar chemical constitution and physicochemical properties to above-mentioned vincamine and esters thereof, when the preparation transdermal absorption formulation, can adopt similar methods, reach the transdermal effect of expection.
Described oil phase, its be further characterized in that the preferred glyceryl linoleate of described oil phase (Maisine 35-1), isostearyl isostearate ester (Isostearyl Isostearate), caprylic/capric triglyceride (Captex 355, Captex 200, Miglyol 810/812), isopropyl myristate (IPM), isopropyl palmitate (IPP), Polyethylene Glycol glyceryl laurate ester (Gelucire 44/14),
WL 1944CS, Labrafil WL 2125CS, Labrafac
Oleic acid (Oleic acid), Oleum Glycines (Soybean oil), oleic acid sorbitol ester (Arlacel 80), olein: propylene glycol (90: 10) (Arlacel 86), Oleum Cocois caprylic/capric glyceride (Capmul MCM), the acetylizad monoglyceride of purification (Myvacet), purification Oleum helianthi monoglyceride (Myverol 18-92) a kind of or their mixture.
Related surfactant comprises Polyethylene Glycol-8-caprylic/capric glyceride (Labrasol), polyoxyethylene castor oil (Cremophor EL), polyoxyethylene hydrogenated Oleum Ricini (Cremophor RH40), Labrafac M 1944CS, Oleum Cocois caprylic/capric polyethyleneglycol glyceride (Labrafac CM 10), Tween 80 (Tween 80), a kind of in the sorbester p17 (Span 80) or their mixture, Polyethylene Glycol-8-caprylic/capric glyceride (Labrasol) wherein, polyoxyethylene castor oil (Cremophor EL), polyoxyethylene hydrogenated Oleum Ricini (Cremophor RH40), Tween 80 (Tween 80), (Span80) is more commonly used for sorbester p17, and effect is better;
Related aqueous favoring comprises the hydrochloric acid solution of redistilled water, normal saline, phosphate buffer, 0.1N, and generally redistilled water is comparatively commonly used in preparation capable of permeating skin, when using buffer salt, should control pH 6.8 or 7.4;
Related cosurfactant comprise ethylene glycol, propylene glycol, ethanol, isopropyl alcohol, glycerol, polyglycereol,
The two isostearates (Plurol Diisostearique) of polyglycereol-6-dioleate (Plurol oleique), polyglycereol-3-, octoxinol-11 and polysorbate (Solubilisant gamma 2420), ethylene glycol monomethyl ether (
P), the ethyoxyl diethylene glycol (
CG) a kind of in or their mixture, wherein preferred cosurfactant is
Polyglycereol-6-dioleate (Plurol oleique), the two isostearates (Plurol Diisostearique) of polyglycereol-3-, polyglycereol-6-isostearate (Plurol isostearique), octoxinol-11 and polysorbate and Polyethylene Glycol-40 castor oil hydrogenated (Solubilisant gamma 2428), ethylene glycol monomethyl ether (
P), the ethyoxyl diethylene glycol (
CG) a kind of in or their mixture;
Described with the water-based patch of microemulsion as carrier, the mixed solution that it further is characterized as described pastille microemulsion is described component; Described high molecular polymer is a polyacrylate, is mainly the mixture of sodium polyacrylate or polyacrylic acid and sodium polyacrylate; Described cross-linking agent is mainly and comprises aluminium hydroxide; Described organic acid is mainly and is tartaric acid; Described wetting agent comprises a kind of in glycerol, propylene glycol, sorbitol, the Polyethylene Glycol or their mixture, preferably glycerine and Polyethylene Glycol; Related penetration enhancer comprises a kind of in terpenoid, quintessence oil, azone, almond oil polyethyleneglycol glyceride (Labrafil M1944CS), ethylene glycol monomethyl ether (Transcutol P), Polyethylene Glycol-8-caprylic/capric glyceride (Labrosol), the N methyl-ketopyrrolidine (NMP) or their mixture, according to applicant's practical experience, terpenoid (as: Borneolum Syntheticum, Mentholum etc.), azone, quintessence oil and N methyl-ketopyrrolidine (NMP) are comparatively commonly used in the preparation of being applied for.
Described microemulsion formulation preparation technology, mainly the problem of Xie Jueing is temperature and mixing speed, it is further characterized in that in the preparation process, some oil phase, surfactant at room temperature is solid or semisolid, need heating in water bath during use, as glyceryl linoleate (Maisine35-1), Polyethylene Glycol glyceryl laurate ester (Gelucire 44/14), oleic acid (Oleic acid) need be in 40～50 ℃ water-bath heating for dissolving, polyoxyethylene castor oil (CremophorEL), polyoxyethylene hydrogenated Oleum Ricini (Cremophor RH40) need be in 30～40 ℃ water-bath heating for dissolving.
Among the described microemulsion preparation technology, it is further characterized in that described stirring is meant that rotating speed is 10～200rpm, and temperature is 25 ± 1 ℃, and the inventor advises that preferred rotating speed is 50rpm.
Described key is the addition sequence of component with the preparation technology of microemulsion as the water-based patch of carrier, should at first cross-linking agent be added in the glycerol, fully disperses, and adds high molecular polymers such as polyacrylic acid, sodium polyacrylate again, mixes to form gel.Again organic acid is dissolved in the distilled water, add the organic acid aqueous solution in the gel slowly, add on one side, firmly stir on one side, the patch substrate transparent, that viscosity is moderate finally formed, under agitation add above-mentioned pastille microemulsion formulation then, add Percutaneous absorption enhancer at last, described patch preparation technology is characterized in that baking temperature should be controlled at 30～50 ℃, at room temperature also can operate, preferred temperature is 35 ℃.
Surfactant that is adopted among the present invention and cosurfactant are nontoxic, safe and effective pharmaceutic adjuvant, do not find any skin irritation.
Stability experiment shows, prepared microemulsion formulation is placed more than 1 year in room temperature, and particle size distribution does not change, and physicochemical properties such as pH value, viscosity all do not change, and illustrate that said preparation has good stable.See Table 1
Description of drawings:
Fig. 1 is the stability experiment investigation table of microemulsion among the present invention
Fig. 2 is the medicine steady-state permeation speed Js (ug/cm of embodiment among the present invention 6 with embodiment 7
2/ s)
Fig. 3 among the present invention according to the vinpocetine microemulsion formulation of embodiment 1 preparation through the Corium Mus penetration curve
Fig. 4 is the penetration curve of vinpocetine (Apovincaminic Acid Ethyl Ester)
Fig. 5 is the penetration curve of apo-Changchun amino acid methyl ester
Fig. 6 is the penetration curve of Licardipine Hydrochloride
Fig. 7 is the penetration curve of hydrochloric acid nimodipine
Fig. 8 is the penetration curve of hydrochloric acid nisoldipine
Fig. 9 is the penetration curve of hydrochloric acid nitrendipine
Fig. 4～Fig. 9 among the present invention according to the different pharmaceutical preparations of embodiment 6 and 7 preparations through the Corium Mus penetration curve
N=6 among the figure; Among Fig. 3～Fig. 9 the accumulation infiltration capacity Q (ug) time (h) of 24h, n=6, mean ± SD);
The specific embodiment
Embodiment 1:
Active medicine 1g
Oleic acid 4g
Cremophor?RH40 15g
Transcutol?P 15g
Redistilled water 65g
Full dose 100g
In the preparation process, oleic acid need be heated in water-bath, add medicine after the dissolving again, with Cremophor RH40 heating for dissolving, mix again, in oily mixture, slowly add entry, promptly get microemulsion formulation with cosurfactant.
Oleic acid still is good Percutaneous absorption enhancer not only as oil phase in the said preparation, can promote the transdermal penetration of insoluble drug.If the active medicine in the said preparation is a vinpocetine, externally show through the Corium Mus permeability test, in 24h, medicine is zero level and discharges, steady-state permeation speed is 0.0417ug/cm2/s, this kind microemulsion formulation is coated on the rabbit skin surface, and zest comprehensive grading index is not found any irritative response all less than 0.5.
Embodiment 2:
Pastille microemulsion (as described in embodiment 1) 6g
Glycerol 35g
Aluminium hydroxide 0.2g
Sodium polyacrylate 5g
Organic acid 0.3g
NMP 5g
Redistilled water 48.5g
Full dose 100g
Preparation method is according to claim 20 and 21 described technologies, and wherein NMP is a transdermal penetration promoter.Said preparation adds the pastille microemulsion in the aqueous patch substrate on the basis of embodiment 1, can make insoluble drug with effectively compatible with aqueous matrix, and by aqueous matrix to cuticular hydration, the percutaneous penetration of drugs amount is improved greatly.Externally increase to 0.062ug/cm2/s through Corium Mus steady-state permeation speed, irritant experiment shows, does not find any erythema, edema phenomenon.
Embodiment 3:
The pastille microemulsion:
Active medicine 3g
Maisine
35-1 5g
Labrasol 20g
Transcutol
10g
P
Redistilled water 62g
Full dose 100g
Preparation method is described with embodiment 1.Maisine 35-1 is as oil phase, and the stability region of made microemulsion formulation is bigger, and the drug loading of microemulsion formulation is increased to some extent.
With the water-based patch of microemulsion as carrier
Pastille microemulsion 5g
Glycerol 40g
Aluminium hydroxide 0.3g
Polyacrylic acid
Sodium 4g
Citric acid 0.2g
Oleum menthae 5g
Redistilled water 45.5g
Full dose 100g
Preparation method is ditto described.Add Oleum menthae in this preparation, can make dermal sensation salubriouser, and had the effect that promotes Transdermal absorption.
Embodiment 4:
The pastille microemulsion:
Active medicine 2g
IPM 3g
Cremophor
25g
EL
Transcutol
15g
P
Redistilled water 55g
Full dose 100g
Preparation method is described with embodiment 1.
With the water-based patch of microemulsion as carrier
Pastille microemulsion 3g
Glycerol/poly-second two
30/10g
Alcohol
Aluminium hydroxide 0.2g
Sodium polyacrylate 4.5g
Citric acid 0.3g
Azone 3g
Redistilled water 49g
Full dose 100g
The preparation method of said preparation is ditto described, wherein as the IPM of oil phase, as the Cremophor EL of surfactant be the good solvent of insoluble drug as the Transcutol P of cosurfactant, can increase the dissolubility of medicine, thereby increase the transdermal penetration of medicine.
Embodiment 5:
The pastille microemulsion:
Active medicine 5g
GELUCIRE44/14 8g
Cremophor?EL 25g
Transcutol?P 10g
Redistilled water 52g
Full dose 100g
Preparation method is described with embodiment 1.
With the water-based patch of microemulsion as carrier
Pastille microemulsion 3g
Glycerol/poly-second two
35/5g
Alcohol
Aluminium hydroxide 0.3g
Sodium polyacrylate 4.0g
Citric acid 0.1g
Azone 5g
Redistilled water 47.6g
Full dose 100g
The preparation method of said preparation is the same, and main advantage is that the oil phase that uses is GELUCIRE44/14, and formed microemulsion zone is very big, and the amount of the active medicine that can load increases to some extent.If in said preparation, improve the ratio of the Transcutol P of Cremophor EL, can also further increase the microemulsion zone, see embodiment 6
Embodiment 6:
The pastille microemulsion:
Active medicine 6
GELUCIRE44/14 8g
Cremophor?EL 26.25g
Transcutol?P 8.75g
Redistilled water 51g
Full dose 100g
Preparation method is described with embodiment 1.
With the water-based patch of microemulsion as carrier
Pastille microemulsion 3g
Glycerol/poly-second two
35g/5g
Alcohol
Aluminium hydroxide 0.3g
Sodium polyacrylate 4.0g
Citric acid 0.1g
Azone 5g
Redistilled water 47.6g
Full dose 100g
The preparation method of said preparation is the same, and in said preparation, the ratio of Cremophor EL and Transcutol P was increased to 3: 1 by 2.5: 1 among the embodiment, and it is 6% that drug loading further increases.
Embodiment 7:
The pastille microemulsion:
Active medicine 6
GELUCIRE44/14 8g
Cremophor?EL 26.25g
Transcutol?P 8.75g
Redistilled water 51g
Full dose 100g
Preparation method is described with embodiment 1.
With the water-based patch of microemulsion as carrier
Pastille microemulsion 3g
Glycerol/poly-second two 35g
Alcohol/5g
Aluminium hydroxide 0.3g
Sodium polyacrylate 4.0g
Citric acid 0.1g
Azone/NMP 3g/2g
Redistilled water 47.6g
Full dose 100g
The preparation method of said preparation is the same, in said preparation, with embodiment 6 unique different compositions that are in penetration enhancer, has used two kinds of penetration enhancers in the said preparation, and this use in conjunction has synergism, makes the percutaneous of medicine absorb further increase.Concrete data are seen accompanying drawing 2 and accompanying drawing 4.
Claims (5)
1. the insoluble drug transdermal absorption formulation is characterized in that, said preparation contains following composition:
A, pastille microemulsion 2～10 weight portions, its prescription is: insoluble drug 0.05～10 weight portion is selected from a kind of in vincamine or vinpocetine or apo-Changchun amino acid methyl ester or hydrochloric acid nitrendipine or Licardipine Hydrochloride or hydrochloric acid nisoldipine or the hydrochloric acid nimodipine; Oil phase 1～10 weight portion, be selected from the vegetable oil of Pegylation, medium chain length fatty acid triglyceride, long-chain and medium chain have a kind of in the triglyceride oil of different saturation or their mixture, also are selected from glyceryl linoleate, the isostearyl isostearate ester, caprylic/capric triglyceride Rou Dou Kou isopropyl propionate, isopropyl palmitate, the Polyethylene Glycol glyceryl laurate ester, the oleoyl polyethyleneglycol glyceride, inferior oleoyl polyethyleneglycol glyceride, sad certain herbaceous plants with big flowers acid glycerol three esters, oleic acid, Oleum Glycines, the oleic acid sorbitol ester, olein: propylene glycol (90: 10), Oleum Cocois caprylic/capric glyceride, the acetylizad monoglyceride of purification, purification Oleum helianthi monoglyceride a kind of or their mixture; Surfactant 10～40 weight portions are selected from a kind of of Polyethylene Glycol-8-caprylic/capric glyceride, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini, almond oil polyethyleneglycol glyceride, Oleum Cocois caprylic/capric polyethyleneglycol glyceride, Tween 80, sorbester p17 or their mixture; Cosurfactant 5～30 weight portions, be selected from a kind of of ethylene glycol, propylene glycol, ethanol, isopropyl alcohol, glycerol or their mixture, also be selected from polyglycereol, ethylene glycol monolaurate, polyglycereol-6-dioleate, the two isostearates of polyglycereol-3-, polyglycereol-6-isostearate, octoxinol-11 and polysorbate, octoxinol-1 and polysorbate stagnate and Polyethylene Glycol-40 castor oil hydrogenated, ethylene glycol monomethyl ether, ethyoxyl diethylene glycol a kind of or their mixture; Aqueous favoring 50～80 weight portions, being selected from redistilled water, normal saline, pH is the hydrochloric acid solution of 6.8 or 7.4 phosphate buffers, 0.1N;
B, high molecular polymer 4～6 weight portions are selected from a kind of in polyacrylic acid, the polyacrylate or their mixture;
C, cross-linking agent 0.1～0.4 weight portion are selected from a kind of in aluminium hydroxide, the Glycine sodium or their mixture;
D, organic acid 0.1～0.5 weight portion are selected from a kind of of tartaric acid, lactic acid or their mixture;
E, wetting agent 5～40 weight portions are selected from a kind of of glycerol, propylene glycol, sorbitol, Polyethylene Glycol or their mixture;
F, distilled water 30～50 weight portions;
G, penetration enhancer 3～5 weight portions are selected from a kind of of terpenoid, oleic acid, propylene glycol, ethanol, quintessence oil, azone, almond oil polyethyleneglycol glyceride, ethylene glycol monomethyl ether, Polyethylene Glycol-8-caprylic/capric glyceride, N methyl-ketopyrrolidine or their mixture.
2. the preparation technology of an insoluble drug transdermal absorption formulation as claimed in claim 1, it is characterized in that: a, preparation microemulsion formulation, in the prescription ratio, get insoluble drug, add in the selected oil phase, heating in water bath, stir, it is dissolved fully, add the surfactant and the cosurfactant of full dose again, mix homogeneously, behind the oily mixture that forms homogeneous, in proportion water is added slowly, the limit adds the waterside and stirs, final form transparent, opalescent microemulsion formulation is arranged, place 24h down until balance at 25 ± 1 ℃; B, cross-linking agent is added in the glycerol, fully disperse, add a kind of of polyacrylic acid, polyacrylate or their mixture, mix forming gel; Organic acid solution is added in the gel slowly, firmly stir, finally form the patch substrate transparent, that viscosity is moderate, under agitation add pastille microemulsion formulation a, add Percutaneous absorption enhancer at last, drying, coating, die-cut, packing is promptly.
3. the preparation technology of insoluble drug transdermal absorption formulation according to claim 2, it is characterized in that: in the preparation process, glyceryl linoleate, Polyethylene Glycol glyceryl laurate ester, oleic acid need be in 40～50 ℃ water-bath heating for dissolving, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini need be in 30～40 ℃ water-bath heating for dissolving.
4. the preparation technology of insoluble drug transdermal absorption formulation according to claim 2 is characterized in that: described stirring is meant that rotating speed is 10～200rpm, and temperature is 25 ± 1 ℃.
5. the preparation technology of insoluble drug transdermal absorption formulation according to claim 2 is characterized in that: baking temperature is 30～50 ℃.
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| CNB031116574A CN100413490C (en) | 2003-05-14 | 2003-05-14 | Insoluble medicine transdemal absorption preparation and process for preparing same |
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|---|---|---|---|
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| CN100413490C true CN100413490C (en) | 2008-08-27 |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100381175C (en) * | 2004-10-09 | 2008-04-16 | 山西中医学院 | Microemulsion formulation and its preparation process |
| CN101822652B (en) * | 2009-03-03 | 2013-10-16 | 杭州民生药业有限公司 | Vinpocetine transdermal patch and preparation method thereof |
| CN105669532B (en) * | 2014-12-03 | 2018-11-02 | 广州市恒诺康医药科技有限公司 | Nimodipine soluble derivative and its preparation method and application |
| CN106619491B (en) * | 2017-01-24 | 2019-04-30 | 泉州亚林新材料科技有限公司 | A kind of medicament slow release hydrogel and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0525039A (en) * | 1991-07-15 | 1993-02-02 | Teisan Seiyaku Kk | Plaster containing vinpocetines |
| WO2001007017A1 (en) * | 1999-07-22 | 2001-02-01 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system for administering a calcium antagonist |
-
2003
- 2003-05-14 CN CNB031116574A patent/CN100413490C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0525039A (en) * | 1991-07-15 | 1993-02-02 | Teisan Seiyaku Kk | Plaster containing vinpocetines |
| WO2001007017A1 (en) * | 1999-07-22 | 2001-02-01 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system for administering a calcium antagonist |
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