CN105395517A - Dutasteride soft capsule preparation and preparation process thereof - Google Patents
Dutasteride soft capsule preparation and preparation process thereof Download PDFInfo
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- CN105395517A CN105395517A CN201510920214.5A CN201510920214A CN105395517A CN 105395517 A CN105395517 A CN 105395517A CN 201510920214 A CN201510920214 A CN 201510920214A CN 105395517 A CN105395517 A CN 105395517A
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- Prior art keywords
- soft capsule
- dutasteride
- preparation
- gelatin
- prescription
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- 239000007901 soft capsule Substances 0.000 title claims abstract description 65
- JWJOTENAMICLJG-QWBYCMEYSA-N dutasteride Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)N[C@@H]4CC3)C)CC[C@@]21C)NC1=CC(C(F)(F)F)=CC=C1C(F)(F)F JWJOTENAMICLJG-QWBYCMEYSA-N 0.000 title claims abstract description 53
- 229960004199 dutasteride Drugs 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 39
- 229920000223 polyglycerol Polymers 0.000 claims abstract description 25
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 25
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 12
- 229940079593 drug Drugs 0.000 claims abstract description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 54
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 36
- 108010010803 Gelatin Proteins 0.000 claims description 32
- 229920000159 gelatin Polymers 0.000 claims description 32
- 239000008273 gelatin Substances 0.000 claims description 32
- 235000019322 gelatine Nutrition 0.000 claims description 32
- 235000011852 gelatine desserts Nutrition 0.000 claims description 32
- 238000003756 stirring Methods 0.000 claims description 26
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 24
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 18
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 claims description 18
- 239000004408 titanium dioxide Substances 0.000 claims description 18
- 239000003292 glue Substances 0.000 claims description 14
- 239000002775 capsule Substances 0.000 claims description 13
- 206010030113 Oedema Diseases 0.000 claims description 12
- 238000004513 sizing Methods 0.000 claims description 12
- 210000000952 spleen Anatomy 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 7
- 239000006187 pill Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 235000010603 pastilles Nutrition 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 238000010792 warming Methods 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 14
- 229940049964 oleate Drugs 0.000 abstract 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 abstract 1
- 239000007903 gelatin capsule Substances 0.000 description 20
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 18
- 238000005070 sampling Methods 0.000 description 10
- 102100020895 Ammonium transporter Rh type A Human genes 0.000 description 5
- 101100301844 Arabidopsis thaliana RH50 gene Proteins 0.000 description 5
- 101150107345 Rhag gene Proteins 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 238000005260 corrosion Methods 0.000 description 4
- 230000007797 corrosion Effects 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- 201000004384 Alopecia Diseases 0.000 description 3
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 3
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000004530 micro-emulsion Substances 0.000 description 3
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 2
- 108010044467 Isoenzymes Proteins 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 description 2
- 231100000360 alopecia Toxicity 0.000 description 2
- 229940054749 avodart Drugs 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical class CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 1
- 239000002677 5-alpha reductase inhibitor Substances 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229960003473 androstanolone Drugs 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007957 coemulsifier Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000000593 microemulsion method Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- -1 polyoxyethylene Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012372 quality testing Methods 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a dutasteride soft capsule preparation, comprising a soft capsule and contents. A prescription for the contents comprises 0.5 g of a dutasteride raw material, 200 to 250 g of labrasol, 30 to 60 g of polyglycerol oleate, 50 to 100 g of medium-chain triglyceride and 0.02 to 0.05 g of 2,6-di-t-butyl p-cresol. The dutasteride soft capsule prepared in the invention is substantially improved in accumulated dissolution in 5 minutes of dissolving-out and enhanced in the dissolving-out efficiency of a main drug in a preceding time period and has good stability and good appearance quality.
Description
Technical field
The present invention relates to technical field of medicine, be specifically related to a kind of dutasteride's soft capsule preparation and preparation technology thereof.
Background technology
Dutasteride is a kind of 5 alpha reductase inhibitors, and 5 alpha-reductases have two hypotypes, i.e. I type and II type, and I type isozyme plays a role to reproductive system, and the testosterone that II type isozyme mainly acts on skin and liver transforms.Dutasteride is 60 times of finasteride to the effect of suppression I type 5 alpha-reductase, also very strong to the effect of II type, dutasteride can suppress testosterone to change dihydrotestosterone (DHT) into, and then suppresses the generation of male DHT, therefore suppresses the prostatic growth of BPH.Be mainly used in the treatment of prostatauxe, male pattern alopecia, seborrheic alopecia, hereditary alopecia clinically.
Dutasteride's dosage form of listing is soft capsule, and commodity are called AVODART Anfu and reach, and are dutasteride to be dissolved in the mixture with butylated hydroxytoluene in sad list/bis-glyceride, then is filled in soft capsule and obtains; But its dissolution is not high or In Vitro Dissolution line is undesirable.
CN103655470A disclosed in, name is called in a kind of dutasteride's self-emulsion composition Chinese patent, disclose method dutasteride being prepared into microemulsion, in that patent, using median chain triglyceride oil as oil phase, polyoxyethylene hydrogenated Oleum Ricini 40 is emulsifying agent, and propylene glycol is co-emulsifier.The open micro emulsion composition of this patent can be prepared into hard capsule, soft capsule, oral liquid formulations or tablet.After being prepared into soft capsule preparation, due to the interpolation of propylene glycol in soft capsule content, be easy to cause pharmaceutical active compounds to migrate in rubber in drying and storage process, thus affect stability and the bioavailability of preparation.
Owing to adding, propylene glycol can move pharmaceutically active, preparation stability and bioavailability have certain influence, therefore adopt the conventional dissolved corrosion not adding the soft capsule preparation of propylene glycol of selecting better, conventional thinner significantly can not improve the dissolution of the soft capsule containing dutasteride, and its dissolution 45 minutes time is difficult to reach more than 80%.Such as, in Chinese patent literature disclosed in CN103830201A, caprylin and median chain triglyceride oil mixed solution prepare soft capsule as oily item, dutasteride's dissolution and stability can be improved preferably, particularly can improve period before stripping as the dissolution rate of first 35 minutes.But a microemulsion method adopted in CN103655470A, be not added with propylene glycol; The preparation of prepared dutasteride's self-microemulsion solid preparation and listing dutasteride's soft capsule (trade name: AVODART) and this patent comparing embodiment 3, in the 0.1mol/L hydrochloric acid solution containing 2% sodium lauryl sulphate, dissolved corrosion is suitable.As can be seen here, when preparation prescription is not identical, considerable influence is had to the dissolved corrosion of principal agent.
Summary of the invention
The object of this invention is to provide a kind of dutasteride's soft capsule preparation.
For reaching above-mentioned purpose, provide a kind of dutasteride's soft capsule preparation in one embodiment of the present of invention, comprise soft capsule and content, content prescription is:
Dutasteride's raw material 0.5g;
Labraso 200g ~ 250g;
Polyglycerol acrylate 30g ~ 60g;
Median chain triglyceride oil 50g ~ 100g;
2,6 ditertiary butyl p cresol 0.02g ~ 0.05g.
In a preferred version of the present invention, content prescription is:
Dutasteride's raw material 0.5g;
Labraso 220g ~ 240g;
Polyglycerol acrylate 40g ~ 50g;
Median chain triglyceride oil 60g ~ 90g;
2,6 ditertiary butyl p cresol 0.03g ~ 0.04g.
In a preferred version of the present invention, content prescription is:
Dutasteride's raw material 0.5g;
Labraso 220g;
Polyglycerol acrylate 45g;
Median chain triglyceride oil 75g;
2,6 ditertiary butyl p cresol 0.035g.
In a preferred version of the present invention, content prescription is:
Dutasteride's raw material 0.5g;
Labraso 235g;
Polyglycerol acrylate 48g;
Median chain triglyceride oil 78g;
2,6 ditertiary butyl p cresol 0.04g.
In a preferred version of the present invention, the prescription of soft capsule is:
Gelatin 140mg ~ 180mg;
Glycerol 70mg ~ 100mg;
Yellow ferric oxide 0.1mg ~ 0.4mg;
Titanium dioxide 1mg ~ 3mg.
In a preferred version of the present invention, the prescription of soft capsule is:
Gelatin 160mg;
Glycerol 85mg;
Yellow ferric oxide 0.28mg;
Titanium dioxide 2mg.
In a preferred version of the present invention, the prescription of soft capsule is:
Gelatin 155mg;
Glycerol 92mg;
Yellow ferric oxide 0.3mg;
Titanium dioxide 2.5mg.
Another object of the present invention improves a kind of technique preparing dutasteride's soft capsule preparation, comprises the following steps:
(1) content is prepared: get the Labraso of recipe quantity, polyglycerol acrylate and median chain triglyceride oil and stir, dutasteride's crude drug and 2 of recipe quantity is added after intensification, 6-ditertbutylparacresol, be down to room temperature after continuing to stir, obtain content;
(2) soft capsule is prepared: the glycerol getting recipe quantity adds in being placed in of water glue tank and is uniformly mixed, and then adds the titanium dioxide and yellow ferric oxide mix homogeneously that sieve, then adds gelatin and be heated to 60 DEG C ~ 80 DEG C; Continue to be stirred to gelatin to dissolve completely; Opening vacuum after Gelatin makes glue degassed, lowers the temperature after degassed;
(3) pill: use soft capsule that Contents Fill is inner to soft capsule, sizing, drying, obtain pastille soft capsule.
In a preferred version of the present invention, Labraso, polyglycerol acrylate and median chain triglyceride oil stir, and add dutasteride's crude drug and 2,6 ditertiary butyl p cresol after being warming up to 40 DEG C.
In a preferred version of the present invention, the capsule severe edema due to hypofunction of the spleen of pastille soft capsule is divided into 8% ~ 12%.
Polyglycerol acrylate of the present invention buys the product polyglycerol acrylate of praising method lion in France.
In sum, the present invention has the following advantages:
Dutasteride's soft capsule of the present invention, can significantly improve the stripping accumulation dissolution of 5 minutes, improves the dissolution efficiency of principal agent in the front time period; Have good stability, product appearance quality is good.Secondly the present invention is by the optimized choice to component, reduces the harmful effect of propylene glycol to principal agent migration, stability, dissolution and bioavailability.
Accompanying drawing explanation
Fig. 1 is one of them embodiment of the present invention and commercially available prod dissolution contrast table.
Detailed description of the invention
Embodiment 1
Dutasteride's soft capsule preparation content prescription:
Dutasteride's raw material 0.5g; Labraso 220g;
Polyglycerol acrylate 45g; Median chain triglyceride oil 75g;
2,6 ditertiary butyl p cresol 0.035g.
Soft capsule prescription:
Gelatin 160mg; Glycerol 85mg;
Yellow ferric oxide 0.28mg; Titanium dioxide 2mg.
Preparation method:
(1) content is prepared: get the Labraso of recipe quantity, polyglycerol acrylate and median chain triglyceride oil and stir, dutasteride's crude drug and 2 of recipe quantity is added after being warmed up to 40 DEG C, 6-ditertbutylparacresol, continue to stir 1h and be down to room temperature after evenly, obtain content;
(2) soft capsule is prepared: the glycerol getting recipe quantity adds in being placed in of water glue tank and is uniformly mixed, and then adds titanium dioxide and the yellow ferric oxide mix homogeneously of 80 mesh sieves, and then adds gelatin and be heated to 70 DEG C; Continue to stir 1h to stop stirring after gelatin dissolves completely; Opening vacuum after Gelatin keeps vacuum bag-0.09Mpa to make the degassed 30min of glue, lowers the temperature 60 DEG C after degassed, for subsequent use after leaving standstill 24h;
(3) pill: encapsulating machine heats sprinkler body after debugging; Adjustment revolving die pressure, is advisable just to extrude soft gelatin capsule, avoids pressure to cross conference mold damage.Carry out loading amount adjustment, sampling detects the crack quality, outward appearance, the content weight that extrude soft gelatin capsule, adjusts in time, till meeting the requirements; Open cylinder, by the sizing of the soft gelatin capsule of compacting; The soft gelatin capsule of compacting is taken out after cylinder sizing, is placed in 30 DEG C, dry in the environment of below RH50%, and sampling at any time detects the capsule severe edema due to hypofunction of the spleen divides, when the capsule severe edema due to hypofunction of the spleen divides 8% ~ 12% time, stop dry.
Embodiment 2
Dutasteride's soft capsule preparation content prescription:
Dutasteride's raw material 0.5g; Labraso 225g;
Polyglycerol acrylate 50g; Median chain triglyceride oil 72g;
2,6 ditertiary butyl p cresol 0.038g.
Soft capsule prescription:
Gelatin 165mg; Glycerol 83mg;
Yellow ferric oxide 0.27mg; Titanium dioxide 2.2mg.
Preparation method:
(1) content is prepared: get the Labraso of recipe quantity, polyglycerol acrylate and median chain triglyceride oil and stir, dutasteride's crude drug and 2 of recipe quantity is added after being warmed up to 40 DEG C, 6-ditertbutylparacresol, continue to stir 1h and be down to room temperature after evenly, obtain content;
(2) soft capsule is prepared: the glycerol getting recipe quantity adds in being placed in of water glue tank and is uniformly mixed, and then adds titanium dioxide and the yellow ferric oxide mix homogeneously of 80 mesh sieves, and then adds gelatin and be heated to 70 DEG C; Continue to stir 1h to stop stirring after gelatin dissolves completely; Opening vacuum after Gelatin keeps vacuum bag-0.09Mpa to make the degassed 30min of glue, lowers the temperature 60 DEG C after degassed, for subsequent use after leaving standstill 24h;
(3) pill: encapsulating machine heats sprinkler body after debugging; Adjustment revolving die pressure, is advisable just to extrude soft gelatin capsule, avoids pressure to cross conference mold damage.Carry out loading amount adjustment, sampling detects the crack quality, outward appearance, the content weight that extrude soft gelatin capsule, adjusts in time, till meeting the requirements; Open cylinder, by the sizing of the soft gelatin capsule of compacting; The soft gelatin capsule of compacting is taken out after cylinder sizing, is placed in 30 DEG C, dry in the environment of below RH50%, and sampling at any time detects the capsule severe edema due to hypofunction of the spleen divides, when the capsule severe edema due to hypofunction of the spleen divides 8% ~ 12% time, stop dry.
Embodiment 3
Dutasteride's soft capsule preparation content prescription:
Dutasteride's raw material 0.5g; Labraso 220g;
Polyglycerol acrylate 45g; Median chain triglyceride oil 75g;
Soft capsule prescription:
Gelatin 160mg; Glycerol 85mg;
Yellow ferric oxide 0.28mg; Titanium dioxide 2mg.
Preparation method:
(1) content is prepared: get the Labraso of recipe quantity, polyglycerol acrylate and median chain triglyceride oil and stir, the dutasteride's crude drug adding recipe quantity after being warmed up to 40 DEG C continues to stir 1h and be down to room temperature after evenly, obtains content;
(2) soft capsule is prepared: the glycerol getting recipe quantity adds in being placed in of water glue tank and is uniformly mixed, and then adds titanium dioxide and the yellow ferric oxide mix homogeneously of 80 mesh sieves, and then adds gelatin and be heated to 70 DEG C; Continue to stir 1h to stop stirring after gelatin dissolves completely; Opening vacuum after Gelatin keeps vacuum bag-0.09Mpa to make the degassed 30min of glue, lowers the temperature 60 DEG C after degassed, for subsequent use after leaving standstill 24h;
(3) pill: encapsulating machine heats sprinkler body after debugging, control temperature is at 35 DEG C; Adjustment revolving die pressure, is advisable just to extrude soft gelatin capsule, avoids pressure to cross conference mold damage.Carry out loading amount adjustment, sampling detects the crack quality, outward appearance, the content weight that extrude soft gelatin capsule, adjusts in time, till meeting the requirements; Open cylinder, by the sizing of the soft gelatin capsule of compacting; The soft gelatin capsule of compacting is taken out after cylinder sizing, is placed in 30 DEG C, dry in the environment of below RH50%, and sampling at any time detects the capsule severe edema due to hypofunction of the spleen divides, when the capsule severe edema due to hypofunction of the spleen divides 8% ~ 12% time, stop dry.
Embodiment 4
Dutasteride's soft capsule preparation content prescription:
Dutasteride's raw material 0.5g; Labraso 220g;
Polyglycerol acrylate 45g; Median chain triglyceride oil 75g;
Butylated hydroxyanisole BHA0.035g.
Soft capsule prescription:
Gelatin 160mg; Glycerol 85mg;
Yellow ferric oxide 0.28mg; Titanium dioxide 2mg.
Preparation method:
(1) content is prepared: get the Labraso of recipe quantity, polyglycerol acrylate and median chain triglyceride oil and stir, the dutasteride's crude drug and the Butylated hydroxyanisole BHA continuation stirring 1h that add recipe quantity after being warmed up to 40 DEG C are down to room temperature after evenly, obtain content;
(2) soft capsule is prepared: the glycerol getting recipe quantity adds in being placed in of water glue tank and is uniformly mixed, and then adds titanium dioxide and the yellow ferric oxide mix homogeneously of 80 mesh sieves, and then adds gelatin and be heated to 70 DEG C; Continue to stir 1h to stop stirring after gelatin dissolves completely; Opening vacuum after Gelatin keeps vacuum bag-0.09Mpa to make the degassed 30min of glue, lowers the temperature 60 DEG C after degassed, for subsequent use after leaving standstill 24h;
(3) pill: encapsulating machine heats sprinkler body after debugging; Adjustment revolving die pressure, is advisable just to extrude soft gelatin capsule, avoids pressure to cross conference mold damage.Carry out loading amount adjustment, sampling detects the crack quality, outward appearance, the content weight that extrude soft gelatin capsule, adjusts in time, till meeting the requirements; Open cylinder, by the sizing of the soft gelatin capsule of compacting; The soft gelatin capsule of compacting is taken out after cylinder sizing, is placed in 30 DEG C, dry in the environment of below RH50%, and sampling at any time detects the capsule severe edema due to hypofunction of the spleen divides, when the capsule severe edema due to hypofunction of the spleen divides 8% ~ 12% time, stop dry.
Embodiment 5
Dutasteride's soft capsule preparation content prescription:
Dutasteride's raw material 0.5g; Labraso 220g;
Polyglycerol acrylate 45g; Median chain triglyceride oil 75g;
Sodium pyrosulfite 0.035g.
Soft capsule prescription:
Gelatin 160mg; Glycerol 85mg;
Yellow ferric oxide 0.28mg; Titanium dioxide 2mg.
Preparation method:
(1) content is prepared: get the Labraso of recipe quantity, polyglycerol acrylate and median chain triglyceride oil and stir, dutasteride's crude drug and the sodium pyrosulfite of recipe quantity is added after being warmed up to 40 DEG C, continue to stir 1h and be down to room temperature after evenly, obtain content;
(2) soft capsule is prepared: the glycerol getting recipe quantity adds in being placed in of water glue tank and is uniformly mixed, and then adds titanium dioxide and the yellow ferric oxide mix homogeneously of 80 mesh sieves, and then adds gelatin and be heated to 70 DEG C; Continue to stir 1h to stop stirring after gelatin dissolves completely; Opening vacuum after Gelatin keeps vacuum bag-0.09Mpa to make the degassed 30min of glue, lowers the temperature 60 DEG C after degassed, for subsequent use after leaving standstill 24h;
(3) pill: encapsulating machine heats sprinkler body after debugging, control temperature is at 35 DEG C; Adjustment revolving die pressure, is advisable just to extrude soft gelatin capsule, avoids pressure to cross conference mold damage.Carry out loading amount adjustment, sampling detects the crack quality, outward appearance, the content weight that extrude soft gelatin capsule, adjusts in time, till meeting the requirements; Open cylinder, by the sizing of the soft gelatin capsule of compacting; The soft gelatin capsule of compacting is taken out after cylinder sizing, is placed in 30 DEG C, dry in the environment of below RH50%, and sampling at any time detects the capsule severe edema due to hypofunction of the spleen divides, when the capsule severe edema due to hypofunction of the spleen divides 8% ~ 12% time, stop dry.
Comparative example 3 ~ 5 is contrasted with embodiment 1, detect wherein storage after 6 months principal agent move to the content of soft capsule.Average containing principal agent 1.2% in capsule shells after 6 months in embodiment 1, i.e. migration amount reaches 1.2%, and in embodiment 3 ~ 5, migration amount is all more than 3%; Can obviously reduce migration amount as can be seen here after adding BHT, make the stability of drug component better.
Test example 1: stability experiment
The soft capsule prepared is placed in 25 DEG C and carries out long-time stability experiment, carry out Acceleration study in 40 DEG C.
The soft capsule that self-control sample adopts the method in embodiment 1 and formula preparation to obtain, employing Anfu, commercially available prod reaches; Its stability and quality testing are as table 1:
Table 1: study on the stability experimental result
Test example 2: stripping is tested
Dissolution medium: the hydrochloric acid solution of the 0.1mol/L of the sodium lauryl sulphate containing 2%
Leaching temperature: 37.5 DEG C
Speed of agitator: 50rpm
The dissolution rate adopting HPLC method to measure sample and commercial samples in embodiment 1 under above-mentioned leaching condition is tested, and experimental result is as table 2 and Fig. 1.
Table 2: dissolution rate experimental result
As can be seen here, dutasteride's soft capsule that prescription disclosed by the invention and preparation technology prepare, its stability is a little more than commercially available prod; Can find out in stripping experiment, soft capsule of the present invention had very high dissolution efficiency before 5 minutes, and the dissolved corrosion comparing commercially available prod is quicker, had onset faster action time.
Claims (10)
1. dutasteride's soft capsule preparation, comprises soft capsule and content, it is characterized in that: described content prescription is:
Dutasteride's raw material 0.5g;
Labraso 200g ~ 250g;
Polyglycerol acrylate 30g ~ 60g;
Median chain triglyceride oil 50g ~ 100g;
2,6 ditertiary butyl p cresol 0.02g ~ 0.05g.
2. soft capsule preparation as claimed in claim 1, is characterized in that: described content prescription is:
Dutasteride's raw material 0.5g;
Labraso 220g ~ 240g;
Polyglycerol acrylate 40g ~ 50g;
Median chain triglyceride oil 60g ~ 90g;
2,6 ditertiary butyl p cresol 0.03g ~ 0.04g.
3. soft capsule preparation as claimed in claim 1, is characterized in that: described content prescription is:
Dutasteride's raw material 0.5g;
Labraso 220g;
Polyglycerol acrylate 45g;
Median chain triglyceride oil 75g;
2,6 ditertiary butyl p cresol 0.035g.
4. soft capsule preparation as claimed in claim 1, is characterized in that: described content prescription is:
Dutasteride's raw material 0.5g;
Labraso 235g;
Polyglycerol acrylate 48g;
Median chain triglyceride oil 78g;
2,6 ditertiary butyl p cresol 0.04g.
5. soft capsule preparation as claimed in claim 1, it is characterized in that, the prescription of described soft capsule is:
Gelatin 140mg ~ 180mg;
Glycerol 70mg ~ 100mg;
Yellow ferric oxide 0.1mg ~ 0.4mg;
Titanium dioxide 1mg ~ 3mg.
6. soft capsule preparation as claimed in claim 5, it is characterized in that, the prescription of described soft capsule is:
Gelatin 160mg;
Glycerol 85mg;
Yellow ferric oxide 0.28mg;
Titanium dioxide 2mg.
7. soft capsule preparation as claimed in claim 5, it is characterized in that, the prescription of described soft capsule is:
Gelatin 155mg;
Glycerol 92mg;
Yellow ferric oxide 0.3mg;
Titanium dioxide 2.5mg.
8. prepare the technique of arbitrary dutasteride's soft capsule preparation in claim 1 ~ 7, comprise the following steps:
(1) content is prepared: get the Labraso of recipe quantity, polyglycerol acrylate and median chain triglyceride oil and stir, dutasteride's crude drug and 2 of recipe quantity is added after intensification, 6-ditertbutylparacresol, is down to room temperature after continuing to stir, obtains content;
(2) soft capsule is prepared: the glycerol getting recipe quantity adds in being placed in of water glue tank and is uniformly mixed, and then adds the titanium dioxide and yellow ferric oxide mix homogeneously that sieve, then adds gelatin and be heated to 60 DEG C ~ 80 DEG C; Continue to be stirred to gelatin to dissolve completely; Opening vacuum after Gelatin makes glue degassed, lowers the temperature after degassed;
(3) pill: use soft capsule that Contents Fill is inner to soft capsule, sizing, drying, obtain pastille soft capsule.
9. preparation technology as claimed in claim 8, is characterized in that: described Labraso, polyglycerol acrylate and median chain triglyceride oil stir, adds dutasteride's crude drug and 2,6 ditertiary butyl p cresol after being warming up to 40 DEG C.
10. preparation technology as claimed in claim 8, is characterized in that: the capsule severe edema due to hypofunction of the spleen of described pastille soft capsule is divided into 8% ~ 12%.
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