CN104146966A - Dutasteride self-microemulsion freeze-dried composition and preparation method thereof - Google Patents
Dutasteride self-microemulsion freeze-dried composition and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a dutasteride self-microemulsion freeze-dried composition and a preparation method thereof. The dutasteride self-microemulsion freeze-dried composition disclosed by the invention comprises dutasteride self-microemulsion and a freeze-dried excipient in the weight ratio of (0.5-2):1, wherein the dutasteride self-microemulsion is mainly composed of the following components in percentage by weight: 0.05-0.3% of dutasteride, 5-75% of oil phase, 20-60% of emulsifier, and 4-50% of co-emulsifier. The dutasteride self-microemulsion freeze-dried composition disclosed by the invention is more suitable for preparing dutasteride solid preparations and is capable of increasing the bioavailability of dutasteride.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of dutasteride's self-microemulsion freeze-dried composition and preparation method thereof, and the oral solid formulation that contains this freeze-dried composition.
Background technology
Dutasteride's chemical name: (5 α, 17 β)-(two (trifluoromethyl) phenyl of 2,5-)-3-oxygen-4-azepine-androstane-1-alkene-17-Methanamide, its chemical structural formula is:
Dutasteride is 2nd generation 5 alpha reductase inhibitors, the research and development of You Gelansu company, and the approval of 2002 Nianl0 Yue10You FDA Food and Drug Administrations (FDA) is gone on the market in the U.S., trade name Avodart, the commodity Avolve by name in European market.Be mainly used in clinically the treatment of prostate hyperplasia, male pattern baldness, seborrheic alopecia, hereditary alopecia, that current the first is also unique a kind of medicine that simultaneously suppresses I type and II type 5 alpha-reductases, compare with other 5α-reductase inhibitor, it is useful that dutasteride's dual function is proved to be clinically.In China, 5α-reductase inhibitor and androgen receptor antagonist have approximately occupied the share of half in anti-prostatic hyperplasia market.However, because dutasteride is water-soluble hardly, limited by its physicochemical property, its preparation bioavailability is not high, so dutasteride's preparation of development of new is very necessary.
At present dutasteride's dosage form of listing is soft capsule, and commodity are called AVODART, is dutasteride is dissolved in the mixture of sad list/bis-glyceride and butylated hydroxytoluene, then is filled into soft capsule and obtains.But its dissolution is not high.Its Patent KR100962447 and patent KR101055412, dutasteride is prepared as to the solid state preparation of self emulsifying, can improve to a certain extent dutasteride's dissolution, but it is more complicated to write out a prescription, limited to improving the effect of dutasteride's dissolution, dissolution in having the dissolution fluid of surfactant is suitable with the Avodart of listing, and complicated process of preparation, and the industrialization of restriction technology is used.
The inventor adopts dutasteride's self-microemulsion is made to freeze-dried composition, and the male amine solvent degree of degree of solution is low, and the problem that stripping is slower meanwhile, also makes dutasteride make solid preparation and becomes easier and simpler, is conducive to scale, suitability for industrialized production.
summary of the invention
Object of the present invention provides a kind of dutasteride's self-microemulsion freeze-dried composition, and this freeze-dried composition has solved dutasteride's stripping difficulty, and bioavailability is low, the problem that formulation application scope is narrow, solid preparation industrialization is more difficult etc.
For realizing object of the present invention, provide following embodiment.
In one embodiment, dutasteride's self-microemulsion freeze-dried composition of the present invention, comprise dutasteride's self-microemulsion and lyophilizing excipient, its weight ratio is 0.5～2:1, wherein, described dutasteride's self-microemulsion is mainly comprised of the component of following percentage by weight: 0.05%-0.3% dutasteride, 5%-75% oil phase, 20%-60% emulsifying agent, 4%-50% co-emulsifier.
In the above-described embodiment, dutasteride's self-microemulsion freeze-dried composition of the present invention, described oil phase is selected from vegetable oil, modified vegetable oil, fatty acid ester, isopropyl myristate, median chain triglyceride oil, Capmul MCM C8 and their any mixture, preferably median chain triglyceride oil (MCT), Capmul MCM C8 (CMG) or their mixture; Described emulsifying agent is selected from Tween 80 (Tween80), polyoxyethylene castor oil 35 (Cremophor EL35, abbreviation CrEL35), polyoxyethylene hydrogenated Oleum Ricini 40 (Cremophor RH40), sad certain herbaceous plants with big flowers acid polyethylene glycol glyceride (Labrasol), lecithin and their any mixture, preferably Tween 80, polyoxyethylene castor oil 35, polyoxyethylene hydrogenated Oleum Ricini 40 or their mixture; Described co-emulsifier is selected from propylene glycol, PEG400 (PEG400) and their any mixture; Described excipient is selected from one or more in Dextran 40, maltodextrin, lactose, mannitol, arabic gum, glucose and glycine, preferably glycine, Dextran 40, maltodextrin, mannitol or their mixture.
In a preferred embodiment, dutasteride's self-microemulsion freeze-dried composition of the present invention, comprise dutasteride's self-microemulsion and lyophilizing excipient, its weight ratio is 0.5～2:1, wherein, described dutasteride's self-microemulsion is mainly comprised of the component of following percentage by weight: 0.05%-0.3% dutasteride, 5%-75% oil phase, 20%-60% emulsifying agent, 4%-50% co-emulsifier, and wherein, described oil phase is selected from median chain triglyceride oil (MCT), Capmul MCM C8 (CMG) and their mixture; Described emulsifying agent is selected from Tween 80 (Tween80), polyoxyethylene castor oil 35 (Cremophor EL35, abbreviation CrEL35), polyoxyethylene hydrogenated Oleum Ricini 40 (Cremophor RH40), sad certain herbaceous plants with big flowers acid polyethylene glycol glyceride (Labrasol), their any mixture, preferably Tween 80, polyoxyethylene castor oil 35, polyoxyethylene hydrogenated Oleum Ricini 40 or their mixture; Described co-emulsifier is selected from propylene glycol, PEG400 (PEG400) and their any mixture; Described excipient is selected from one or more in Dextran 40, maltodextrin, lactose, mannitol, arabic gum, glucose and glycine, preferably glycine, Dextran 40, maltodextrin, mannitol or their mixture.
In a more preferred embodiment, dutasteride's self-microemulsion freeze-dried composition of the present invention, comprise dutasteride's self-microemulsion and lyophilizing excipient, its weight ratio is 0.5～2:1, wherein, described dutasteride's self-microemulsion is mainly comprised of the component of following percentage by weight: 0.05%-0.3% dutasteride, 5%-75% oil phase, 20%-60% emulsifying agent, 4%-50% co-emulsifier, and wherein, described oil phase is selected from median chain triglyceride oil (MCT), Capmul MCM C8 (CMG) and their mixture; Described emulsifying agent is selected from Tween 80 (Tween80), polyoxyethylene castor oil 35 (Cremophor EL35, be called for short CrEL35) and their any mixture, described co-emulsifier is selected from propylene glycol, PEG400 (PEG400) and their any mixture; Described excipient is selected from glycine, Dextran 40, maltodextrin, mannitol and their mixture.
Another object of the present invention provides a kind of method of the dutasteride's of preparation self-microemulsion freeze-dried composition, comprises the following steps:
1) in dutasteride, add oil phase, heating for dissolving, add emulsifying agent and co-emulsifier again, after stirring, become self-microemulsion;
2) lyophilizing excipient is scattered in water, then adds in the self-microemulsion of step 1), stir, the O/W type microemulsion making, then carry out lyophilization and obtain dutasteride's self-microemulsion freeze-dried composition;
3) optionally, dutasteride's self-microemulsion freeze-dried composition mixes with pharmaceutic adjuvant and makes solid preparation as tablet or capsule.
In the above-described embodiment, dutasteride's self-microemulsion freeze-dried composition of the present invention, described oil phase is selected from vegetable oil, modified vegetable oil, fatty acid ester, isopropyl myristate, median chain triglyceride oil, Capmul MCM C8 and their any mixture, preferably median chain triglyceride oil (MCT), Capmul MCM C8 (CMG) or their mixture; Described emulsifying agent is selected from Tween 80 (Tween80), polyoxyethylene castor oil 35 (Cremophor EL35, abbreviation CrEL35), polyoxyethylene hydrogenated Oleum Ricini 40 (Cremophor RH40), sad certain herbaceous plants with big flowers acid polyethylene glycol glyceride (Labrasol), lecithin and their any mixture, preferably Tween 80, polyoxyethylene castor oil 35, polyoxyethylene hydrogenated Oleum Ricini 40 or their mixture; Described co-emulsifier is selected from propylene glycol, PEG400 (PEG400) and their any mixture; Described excipient is selected from one or more in Dextran 40, maltodextrin, lactose, mannitol, arabic gum, glucose and glycine, preferably glycine, Dextran 40, maltodextrin, mannitol or their mixture.
A further object of the present invention provides a kind of pharmaceutical composition, comprises dutasteride's self-microemulsion freeze-dried composition of the present invention and pharmaceutic adjuvant.
The pharmaceutical composition of the invention described above, its dosage form can be tablet, also can be granule, capsule etc., pharmaceutic adjuvant comprises filler, disintegrating agent, binding agent or lubricant etc., these adjuvants are all the adjuvants of this area routine, preferably, filler is soluble starch, lactose, microcrystalline Cellulose, xylitol etc. or their mixture, disintegrating agent is cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl methylcellulose, polyvinylpolypyrrolidone, crosslinked carboxymethyl fecula sodium etc., lubricant is magnesium stearate, Pulvis Talci, silicon dioxide or their mixture.The preparation method of its tablet or capsule is the conventional method of this area.
Dutasteride's self-microemulsion freeze-dried composition of the present invention has not only solved the low problem of the oral stripping of dutasteride, has also solved the problem that is only applicable to making soft capsule oral unitary agent.Dutasteride's self-microemulsion freeze-dried composition of the present invention make oral solid formulation as tablet or capsule after; dissolution rate is compared soft capsule and is obviously improved; make reducing in dutasteride's consumption situation; the blood drug level of still remaining valid; reduce dutasteride's side effect, and be applicable to making various conventional oral solid formulations, preparation processing adaptive surface is wider; manufacturing process is simple, is applicable to industrialization and large-scale production.Especially more surprised is makes oral solid formulation by self-microemulsion freeze-dried composition of the present invention and makes oral solid formulation with direct employing self-microemulsion and compare, and its dissolution is more superior, and result of extraction is better.
Accompanying drawing explanation
The In Vitro Dissolution curve chart of Fig. 1 comparing embodiment 1 and embodiment 45-52 preparation.
The specific embodiment
The following example is explained essence of the present invention for further, but does not limit the scope of the invention in any form.
Comparing embodiment 1
Prescription:
Preparation method:
First dutasteride, PVPK17, sucrose ester 15 are together distributed in Capryol 90, and are dissolved in the ethanol of 250g, make the mixed solution of homogenizing.Then above-mentioned solution is added in solidification forming agent microcrystalline Cellulose 256g and crospolyvinylpyrrolidone (Kollidoncl) 50g; carry out the mixed processing of 5min; and utilize No. 16 containers to mention ready-mixed thing; in 60 ℃ of temperature, carry out drying and processing; evaporate organic solvent ethanol; and by above-mentioned wet type granule method, drying in the granulate mixture producing; fusion microcrystalline Cellulose (AvicelPh102) 34.5g; make final admixture, then on suitable tablet machine, be crushed to tablet.
Comparing embodiment 2
A) dutasteride's self-microemulsion
Prescription:
Above-mentioned dutasteride's self-microemulsion can take following technique to be prepared:
Self-microemulsion is prepared work: precision takes recipe quantity dutasteride, adds recipe quantity oil phase, and 40-50 ℃ of water-bath dissolved it, by recipe quantity, adds emulsifying agent and co-emulsifier, obtains dutasteride's self-microemulsion after stirring.
B) dutasteride's self-microemulsion lyophilized powder
The preparation of self-microemulsion lyophilized powder:
Lyophilizing excipient is scattered in purified water, continues to stir until excipient dissolves completely; Add dutasteride's self-microemulsion again, stir 10min, the O/W type microemulsion making, pours into this microemulsion in cillin bottle, to carry out lyophilization.
Result:
This prescription cannot obtain good dutasteride's self-microemulsion freeze-dried powder.
Comparing embodiment 3
A, dutasteride's self-microemulsion
Prescription:
Above-mentioned dutasteride's self-microemulsion can take following technique to be prepared:
Self-microemulsion is prepared work: precision takes recipe quantity dutasteride, adds recipe quantity oil phase, and 40-50 ℃ of water-bath dissolved it, by recipe quantity, adds emulsifying agent and co-emulsifier, obtains dutasteride's self-microemulsion after stirring.
B, dutasteride's self-microemulsion lyophilized powder
Prescription:
The preparation of self-microemulsion lyophilized powder:
Lyophilizing excipient is scattered in purified water, continues to stir until excipient dissolves completely; Add dutasteride's self-microemulsion again, stir 10min, the O/W type microemulsion making, pours into this microemulsion in cillin bottle, to carry out lyophilization.
Lyophilizing result:
| ?character | redissolution character |
| cellular, translucent. | redissolve slower, and muddy |
This prescription cannot obtain good dutasteride's self-microemulsion freeze-dried powder because lactose consumption is lower.
Comparing embodiment 4
Dutasteride's self-microemulsion
Prescription:
Above-mentioned dutasteride's self-microemulsion can take following technique to be prepared:
Self-microemulsion is prepared work: precision takes recipe quantity dutasteride, adds recipe quantity oil phase, and 40-50 ℃ of water-bath dissolved it, by recipe quantity, adds emulsifying agent and co-emulsifier, obtains dutasteride's self-microemulsion after stirring.
Dutasteride's self-microemulsion lyophilized powder
Prescription:
The preparation of self-microemulsion lyophilized powder:
Lyophilizing excipient is scattered in purified water, continues to stir until excipient dissolves completely; Add dutasteride's self-microemulsion again, stir 10min, the O/W type microemulsion making, pours into this microemulsion in cillin bottle, to carry out lyophilization.
Result:
This prescription cannot obtain good dutasteride's self-microemulsion freeze-dried powder because lactose consumption is higher.
Comparing embodiment 5
Dutasteride's self-microemulsion
Prescription:
Above-mentioned dutasteride's self-microemulsion can take following technique to be prepared:
Self-microemulsion is prepared work: precision takes recipe quantity dutasteride, adds recipe quantity oil phase, and 40-50 ℃ of water-bath dissolved it, by recipe quantity, adds emulsifying agent and co-emulsifier, obtains dutasteride's self-microemulsion after stirring.
Dutasteride's self-microemulsion lyophilized powder
Prescription:
The preparation of self-microemulsion lyophilized powder:
Lyophilizing excipient is scattered in purified water, continues to stir until excipient dissolves completely; Add dutasteride's self-microemulsion again, stir 10min, the O/W type microemulsion making, pours into this microemulsion in cillin bottle, to carry out lyophilization.
Result:
This prescription cannot obtain good dutasteride's self-microemulsion freeze-dried powder because mannitol consumption is too high.
Embodiment 1～22
Self-emulsion composition
Prescription:
Preparation technology:
Above-mentioned dutasteride's self-microemulsion can take following technique to be prepared.
Self-microemulsion is prepared work: precision takes recipe quantity dutasteride, adds recipe quantity oil phase, and 40-50 ℃ of water-bath dissolved it, by recipe quantity, adds emulsifying agent and co-emulsifier, obtains dutasteride's self-microemulsion after stirring.
Embodiment 23～44
Self-microemulsion dried frozen aquatic products
Prescription:
The preparation of self-microemulsion lyophilized powder:
Lyophilizing excipient is scattered in purified water, continues to stir until excipient dissolves completely; Add dutasteride's self-microemulsion again, stir 10min, the O/W type microemulsion making, pours into this microemulsion in cillin bottle, to carry out lyophilization.
Dutasteride's self-microemulsion dried frozen aquatic products result:
The freeze-dried powder that above-mentioned prescription obtains is all powdered, after redissolution, all can obtain clear liquid.
Embodiment 45 Peroral solid dosage form capsules
Prescription forms:
Dutasteride's self-microemulsion dried frozen aquatic products (deriving from embodiment 26) 29g(is containing dutasteride 14.5mg)
Starch 29g
Preparation method: soluble starch 29g, under stirring, add dutasteride's self-microemulsion dried frozen aquatic products (29g(containing dutasteride 14.5mg) of embodiment 26, after mixing, encapsulated by dutasteride 0.5mg/ grain content, make altogether 29 of Peroral solid dosage form capsules.
Embodiment 45 A Peroral solid dosage form capsules (as the comparative example of embodiment 45)
Prescription forms:
Dutasteride's self-microemulsion (deriving from embodiment 4) 29g(is containing dutasteride 14.5mg)
Starch 58g
Preparation method: starch 58g, under stirring, add dutasteride's self-microemulsion (29g(containing dutasteride 14.5mg) of embodiment 4, after mixing, encapsulated by dutasteride 0.5mg/ grain content, make altogether 29 of Peroral solid dosage form capsules.
Embodiment 45B Peroral solid dosage form capsule (as the comparative example of embodiment 45)
Prescription forms:
Dutasteride's self-microemulsion (deriving from embodiment 4) 29g(is containing dutasteride 14.5mg)
Starch 29g
Mannitol 58g
Preparation method: under agitation the starch of recipe quantity, mannitol are joined to dutasteride's self-microemulsion 29g(of embodiment 4 containing dutasteride 14.5mg) in, after mixing, encapsulated by dutasteride 0.5mg/ grain content, make altogether 29 of Peroral solid dosage form capsules.
Embodiment 46 Peroral solid dosage form capsules
Prescription forms:
Dutasteride's self-microemulsion dried frozen aquatic products (deriving from embodiment 29) 29g(is containing dutasteride 43.4mg)
Starch 29g
Preparation method: soluble starch 29g, under stirring, add dutasteride's self-microemulsion dried frozen aquatic products (containing dutasteride 43.4mg) of embodiment 29, after mixing, encapsulated by dutasteride 0.5mg/ grain content, make altogether 86 of Peroral solid dosage form capsules.
Embodiment 47 Peroral solid dosage form capsules
Prescription forms:
Dutasteride's self-microemulsion dried frozen aquatic products (deriving from embodiment 32) 29g(is containing dutasteride 43.4mg)
Silica 1 9g
Preparation method: silica 1 9g, under stirring, add dutasteride's self-microemulsion dried frozen aquatic products (containing dutasteride 43.4mg) of embodiment 32, after mixing, encapsulated by dutasteride 0.5mg/ grain content, make altogether 86 of Peroral solid dosage form capsules.
Embodiment 47 A Peroral solid dosage form capsules (as the comparative example of embodiment 47)
Prescription forms:
Dutasteride's self-microemulsion (deriving from embodiment 10) 29g(is containing dutasteride 43.4mg)
Silicon dioxide 58g
Preparation method: silicon dioxide 58g, under stirring, add dutasteride's self-microemulsion (containing dutasteride 43.4mg) of embodiment 10, after mixing, encapsulated by dutasteride 0.5mg/ grain content, make altogether 86 of Peroral solid dosage form capsules.
Embodiment 48 Peroral solid dosage form capsules
Prescription forms:
Dutasteride's self-microemulsion dried frozen aquatic products (deriving from embodiment 39) 29g(is containing dutasteride 43.4mg)
Starch 29g
Preparation method: soluble starch 29g, under stirring, add dutasteride's self-microemulsion dried frozen aquatic products (containing dutasteride 43.4mg) of embodiment 29, after mixing, encapsulated by dutasteride 0.5mg/ grain content, make altogether 86 of Peroral solid dosage form capsules.
Embodiment 49 tablets
Prescription forms:
Dutasteride's self-microemulsion dried frozen aquatic products (deriving from embodiment 26) 29g(is containing dutasteride 14.5mg)
Starch 28g
Cross-linking sodium carboxymethyl cellulose 2g
Magnesium stearate 2.2g
Preparation method: soluble starch 28g, under stirring, add dutasteride's self-microemulsion dried frozen aquatic products 29g(of embodiment 26 containing dutasteride 14.5mg), then add successively 2g cross-linking sodium carboxymethyl cellulose, 2.2g magnesium stearate, after mixing, press content tabletting, must be containing 29 of tablet.
Embodiment 50 tablets
Prescription forms:
Dutasteride's self-microemulsion dried frozen aquatic products (deriving from embodiment 35) 29g(is containing dutasteride 43.4mg)
Microcrystalline Cellulose 10g
Cross-linking sodium carboxymethyl cellulose 0.6g
Magnesium stearate 0.2g
Preparation method: add successively under stirring dutasteride's self-microemulsion dried frozen aquatic products 29g(of embodiment 35 containing dutasteride 43.4mg), microcrystalline Cellulose 10g, cross-linking sodium carboxymethyl cellulose 0.6g, magnesium stearate 0.2g, after mixing, press content tabletting, must be containing 86 of tablet.
Embodiment 50A tablet (as the comparative example of embodiment 50)
Prescription forms:
Dutasteride's self-microemulsion (deriving from embodiment 13) 29g(is containing dutasteride 86.8mg)
Microcrystalline Cellulose 87g
Cross-linking sodium carboxymethyl cellulose 1.8g
Magnesium stearate 0.6g
Preparation method: add successively under stirring dutasteride's self-microemulsion 29g(of embodiment 13 containing dutasteride 86.8mg), microcrystalline Cellulose 87g, cross-linking sodium carboxymethyl cellulose 1.8g, magnesium stearate 0.6g, after mixing, by content tabletting, must be containing 172 of tablet.
Embodiment 51 tablets
Prescription forms:
Dutasteride's self-microemulsion dried frozen aquatic products (deriving from embodiment 32) 29g(is containing dutasteride 43.4mg)
Xylitol 14g
Microcrystalline Cellulose 3.5g
Cross-linking sodium carboxymethyl cellulose 0.63g
Magnesium stearate 0.21g
Preparation method: xylitol 14g, under stirring, add dutasteride's self-microemulsion dried frozen aquatic products 29g(of embodiment 32 containing dutasteride 43.4mg), add successively again 3.5g microcrystalline Cellulose, 0.63g cross-linking sodium carboxymethyl cellulose, 0.21g magnesium stearate, after mixing, press content tabletting, must be containing 86 of tablet.
Embodiment 52 tablets
Prescription forms:
Dutasteride's self-microemulsion dried frozen aquatic products (deriving from embodiment 39) 29g(is containing dutasteride 43.4mg)
Starch 14g
Microcrystalline Cellulose 3.5g
Cross-linking sodium carboxymethyl cellulose 0.63g
Magnesium stearate 0.21g
Preparation method: soluble starch 14g, under stirring, add dutasteride's self-microemulsion dried frozen aquatic products 29g(of embodiment 39 containing dutasteride 43.4mg), add successively again 3.5g microcrystalline Cellulose, 0.63g cross-linking sodium carboxymethyl cellulose, 0.21g magnesium stearate, after mixing, press content tabletting, must be containing 86 of tablet.
Embodiment 53 dissolution determinations
Measure comparing embodiment 1, embodiment 45A and 45B, embodiment 47A, embodiment 50A, and preparation and the preparation of embodiment 49,50,51,52 and the stripping behavior of dutasteride's soft capsule of listing in 0.1mol/l aqueous hydrochloric acid solution of the random embodiment 45,46,47,48 selecting.
Data from table 1, table 2, dutasteride's self-microemulsion freeze-dried powder preparation of the present invention (embodiment 45,46,47,48,49,50,51,52) 60min accumulation dissolution in 0.1mol/l hydrochloric acid solution is higher than comparing embodiment 1, embodiment 45A, embodiment 47A, embodiment 50A, embodiment 45B, and far away higher than commercially available dutasteride's soft capsule (trade name: AVODART), under comparatively gentle leaching condition, the 45min dissolution that does not add surfactant in dissolution medium reaches more than 85%.
Embodiment 54 dissolution determinations
Relatively make embodiment dutasteride self-micro emulsion formulation, comparing embodiment and listing dutasteride soft capsule (trade name: stripping behavior AVODART) by oneself.
The result of table 3, table 4 shows, dutasteride's self-microemulsion lyophilized powder solid preparation of the present invention (embodiment 45,46,47,48,49,50,51,52) and listing dutasteride soft capsule (trade name: AVODART) and the preparation of comparing embodiment 1, embodiment 45A, embodiment 47A, embodiment 50A, embodiment 45B, stripping behavior is suitable in the 0.1mol/l hydrochloric acid solution that contains 1% sodium lauryl sulphate.Owing to having added surfactant in dissolution medium, can not distinguish the quality of each comparison dissolution.
Claims (10)
1. dutasteride's self-microemulsion freeze-dried composition, comprise dutasteride's self-microemulsion and lyophilizing excipient, its weight ratio is 0.5～2:1, wherein, described dutasteride's self-microemulsion is mainly comprised of the component of following percentage by weight: 0.05%-0.3% dutasteride, 5%-75% oil phase, 20%-60% emulsifying agent, 4%-50% co-emulsifier.
2. compositions as claimed in claim 1, described oil phase is selected from vegetable oil, modified vegetable oil, fatty acid ester, isopropyl myristate, median chain triglyceride oil, Capmul MCM C8 and their any mixture, preferably median chain triglyceride oil, Capmul MCM C8 or their mixture.
3. compositions as claimed in claim 1, described emulsifying agent is selected from Tween 80, polyoxyethylene castor oil 35, polyoxyethylene hydrogenated Oleum Ricini 40, sad certain herbaceous plants with big flowers acid polyethylene glycol glyceride, lecithin and their any mixture, preferably Tween 80, polyoxyethylene castor oil 35, polyoxyethylene hydrogenated Oleum Ricini 40 or their mixture.
4. compositions as claimed in claim 1, described co-emulsifier is selected from propylene glycol, PEG400 and their any mixture.
5. compositions as claimed in claim 1, described excipient is selected from one or more in Dextran 40, maltodextrin, lactose, mannitol, arabic gum, glucose and glycine.
6. compositions as claimed in claim 5, described excipient is glycine, Dextran 40, maltodextrin, mannitol or their mixture.
7. a pharmaceutical composition, the dutasteride's self-microemulsion freeze-dried composition and the pharmaceutic adjuvant that comprise claim 1.
8. a method of preparing dutasteride's self-microemulsion freeze-dried composition, comprises the following steps
1) in dutasteride, add oil phase, heating for dissolving, add emulsifying agent and co-emulsifier again, after stirring, become self-microemulsion;
2) lyophilizing excipient is scattered in water, adds the self-microemulsion of step 1), in add lyophilizing excipient, stir, the O/W type microemulsion making, carries out lyophilization and obtains dutasteride's self-microemulsion freeze-dried composition;
3) optionally, dutasteride's self-microemulsion freeze-dried composition mixes with pharmaceutic adjuvant and makes tablet or capsule.
9. method as claimed in claim 8, described oil phase is selected from vegetable oil, modified vegetable oil, fatty acid ester, isopropyl myristate, median chain triglyceride oil, Capmul MCM C8 and their any mixture, or described emulsifying agent is selected from Tween 80, polyoxyethylene castor oil 35, polyoxyethylene hydrogenated Oleum Ricini 40, sad certain herbaceous plants with big flowers acid polyethylene glycol glyceride, lecithin and their any mixture, or described co-emulsifier is selected from propylene glycol, PEG400 and their any mixture; Or described excipient is selected from one or more in Dextran 40, maltodextrin, lactose, mannitol, arabic gum, glucose and glycine.
10. method as claimed in claim 9, described oil phase is median chain triglyceride oil, Capmul MCM C8 or their mixture; Or described emulsifying agent is Tween 80, polyoxyethylene castor oil 35, polyoxyethylene hydrogenated Oleum Ricini 40 or their mixture; Or described co-emulsifier is selected from propylene glycol, PEG400 and their any mixture; Or described excipient is selected from one or more in Dextran 40, maltodextrin, mannitol and glycine.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2017503866A (en) * | 2014-12-23 | 2017-02-02 | ハンミ ファーム． シーオー．， エルティーディー． | Composition for self-emulsifying drug delivery system comprising dutasteride |
| WO2017043913A1 (en) * | 2015-09-10 | 2017-03-16 | Yuyu Pharma, Inc. | Pharmaceutical composition including dutasteride and capsule formulation comprising the same |
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| JP2017503866A (en) * | 2014-12-23 | 2017-02-02 | ハンミ ファーム． シーオー．， エルティーディー． | Composition for self-emulsifying drug delivery system comprising dutasteride |
| WO2017043913A1 (en) * | 2015-09-10 | 2017-03-16 | Yuyu Pharma, Inc. | Pharmaceutical composition including dutasteride and capsule formulation comprising the same |
| US10512654B2 (en) | 2015-09-10 | 2019-12-24 | Yuyu Pharma, Inc. | Pharmaceutical composition including dutasteride and capsule formulation comprising the same |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104146966B (en) | 2021-02-26 |
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