CN109288797A - A kind of oral posaconazole preparation and preparation method thereof - Google Patents
A kind of oral posaconazole preparation and preparation method thereof Download PDFInfo
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- CN109288797A CN109288797A CN201811455348.4A CN201811455348A CN109288797A CN 109288797 A CN109288797 A CN 109288797A CN 201811455348 A CN201811455348 A CN 201811455348A CN 109288797 A CN109288797 A CN 109288797A
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- posaconazole
- preparation
- oral
- insoluble carrier
- water insoluble
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- RAGOYPUPXAKGKH-XAKZXMRKSA-N posaconazole Chemical compound O=C1N([C@H]([C@H](C)O)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3C[C@@](CN4N=CN=C4)(OC3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 RAGOYPUPXAKGKH-XAKZXMRKSA-N 0.000 title claims abstract description 67
- 229960001589 posaconazole Drugs 0.000 title claims abstract description 60
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- PVNIQBQSYATKKL-UHFFFAOYSA-N tripalmitin Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 239000001856 Ethyl cellulose Substances 0.000 claims description 10
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 10
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 10
- 229920001249 ethyl cellulose Polymers 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 229960001947 tripalmitin Drugs 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- XHRPOTDGOASDJS-XNTGVSEISA-N cholesteryl stearate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCCCCCCCCCCCC)C1 XHRPOTDGOASDJS-XNTGVSEISA-N 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000007962 solid dispersion Substances 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 3
- 229920005989 resin Polymers 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000007970 homogeneous dispersion Substances 0.000 claims description 2
- 239000000375 suspending agent Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 229920002678 cellulose Polymers 0.000 claims 1
- 239000001913 cellulose Substances 0.000 claims 1
- 239000006185 dispersion Substances 0.000 claims 1
- 239000002245 particle Substances 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 235000019605 sweet taste sensations Nutrition 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 4
- 230000008901 benefit Effects 0.000 abstract description 3
- 239000002552 dosage form Substances 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000006872 improvement Effects 0.000 description 8
- 229940099075 noxafil Drugs 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 206010017533 Fungal infection Diseases 0.000 description 3
- 208000031888 Mycoses Diseases 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 241000228212 Aspergillus Species 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000006069 physical mixture Substances 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- 206010017523 Fungaemia Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 102100021695 Lanosterol 14-alpha demethylase Human genes 0.000 description 1
- 101710146773 Lanosterol 14-alpha demethylase Proteins 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- -1 polyacrylic resinII Chemical compound 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 208000037922 refractory disease Diseases 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000010493 xanthan gum Nutrition 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of oral posaconazole preparations and preparation method thereof, wherein the oral posaconazole preparation includes posaconazole and the water insoluble carrier for dispersing posaconazole, and the mass ratio of posaconazole and water insoluble carrier is 1:0.5-5.The preparation method of disclosed oral posaconazole preparation has simple production process, advantage at low cost.The present invention improves the solubility and dissolution rate of posaconazole, to improve the bioavilability of posaconazole, curative effect is preferable compared with existing dosage form.
Description
Technical field
The invention belongs to technical field of medicine more particularly to a kind of oral posaconazole preparation and preparation method thereof.
Background technique
Currently, fungal infection is generally existing and inevitable, in recent years, since fungal infection and its case fatality rate are in rise
Gesture, posaconazole belongs to antifungal drug in triazole class to be digested to the fungus-caused fungemia of Pseudomonas, Cryptococcus, breathing is read
Road, urinary tract nosomycosis, peritonitis, meningitis etc. have good curative effect.
Posaconazole (posaconazole, trade name Noxafil) is to be ratified by U.S. FDA on September 15th, 2006
A kind of triazole antifungal agent of wide spectrum, for fungal infection (such as aspergillus caused by refractory disease or other drugs drug resistance
Bacterium disease, tulase disease and fusaridiosis etc.), which is developed by Schering-Plough company of the U.S. and is listed, and is a kind of new change
Credit fructification is first antibacterials for preventing to cause lesion by aggressive Aspergillus ratified by FDA, belongs to height
Lipophilicity second generation antifungal, it is identical as other azole antibacterials, the medicine be also by with 14 α of lanosterol-demethylation
The ferroheme confactor of enzyme (CYP51 or Erg11p) active site combines, and inhibits the biosynthesis of fungi ergosterol, destroys
Formation and the integrality of cell membrane and play antibacterial action.
Oral posaconazole form of administration is by posaconazole alkalescent and poor posaconazole free alkali compound at present,
Therefore bioavilability is lower.
Summary of the invention
It is an object of the invention to disclose a kind of oral posaconazole preparation and a kind of system of oral posaconazole preparation
Preparation Method, the posaconazole in the oral preparation not only has very high dissolution rate and bioavilability, and has good stabilization
Property.
To realize above-mentioned first goal of the invention, the present invention provides a kind of oral posaconazole preparations, including moor husky health
The mass ratio of azoles and water insoluble carrier for dispersing posaconazole, the posaconazole and water insoluble carrier is 1:0.5-
5。
As a further improvement of the present invention, water insoluble carrier is ethyl cellulose, cholesterol stearic acid, polyacrylic acid
The mixture of one of resinae and tripalmitin or two or more arbitrary proportions.
As a further improvement of the present invention, water insoluble carrier is ethyl cellulose, and the posaconazole and ethyl are fine
The mass ratio of dimension element is 1:1.3~2.0.
As a further improvement of the present invention, pharmaceutically acceptable excipients can be also added in oral preparation.
As a further improvement of the present invention, excipients are one of suspending agent, sweetener and binder or two kinds
The mixture of any of the above ratio.
The invention also discloses a kind of preparation methods of oral posaconazole preparation, comprising the following steps:
Step (1): water insoluble carrier is dissolved in ethyl alcohol or ethyl acetate, and obtaining mass concentration is 15%~35%
Water insoluble carrier；
Step (2): dispersing posaconazole in the water insoluble carrier made from step (1), make posaconazole with
The mass ratio of water insoluble carrier is 1:0.5~5, is stirred, and volatilizees and is evaporated after homogeneous dispersion, dry, obtains posaconazole solid
Dispersion；
Step (3): pharmaceutically acceptable excipients are added into the posaconazole solid dispersions of step (2), are made
Granule.
As a further improvement of the present invention, the water insoluble carrier in step (1) is ethyl cellulose, cholesterol tristearin
The mixture of one of acid, polyacrylic resins and tripalmitin or two or more arbitrary proportions.
As a further improvement of the present invention, water insoluble carrier is ethyl cellulose, and the posaconazole and ethyl are fine
The mass ratio of dimension element is 1:1.3~2.0.
As a further improvement of the present invention, the temperature that the volatilization in step (2) is evaporated is 65 DEG C~95 DEG C, and volatilization is evaporated
Time be 1.5h~3.5h.
As a further improvement of the present invention, the drying condition in step (2) is vacuum drying or fluidized bed drying.
Compared with prior art, the beneficial effects of the present invention are: disclosed oral posaconazole preparation and its
Preparation method has simple production process, advantage at low cost.The present invention improves the solubility and dissolution rate of posaconazole, from
And the bioavilability of posaconazole is improved, curative effect is preferable compared with existing dosage form.
Specific embodiment
Below with reference to each embodiment, the present invention is described in detail, but it should be stated that, these embodiments are simultaneously
Non- limitation of the present invention, those of ordinary skill in the art are according to these embodiments in made function, method or structure
Equivalent transformation or substitution, all belong to the scope of protection of the present invention within.
Embodiment one
Present embodiment discloses a kind of preparation methods of oral posaconazole preparation, follow the steps below:
Step (1): take ethyl cellulose, cholesterol stearic acid, polyacrylic resinⅡ, tripalmitin each respectively
50g is dissolved in the ethanol solution that mass concentration is 75%, obtains four kinds of water insoluble carrier solution that concentration is 25%.
Step (2): taking 100g posaconazole to be scattered in above-mentioned four kinds of water insoluble carrier solution respectively, stirring, homogeneous
Afterwards, revolving instrument volatilizees under the conditions of 65~95 DEG C is evaporated；It is spray-dried, control inlet air temperature is 115 DEG C, and leaving air temp is
65 DEG C, spray pressure is 0.02Mpa~0.05Mpa, obtains posaconazole solid dispersions.
Respectively by 6g xanthan gum, 9g silica, 9g titanium dioxide, 12g polysorbate 80, the hydration of 5g sodium citrate two
Object, tri- sucrose of 1000g cross 40 mesh screens, mix 15min in 30rpm/min blending tank, obtain physical mixture.
Step (3): it is separately added into physical mixture into four kinds of water insoluble carriers, blending tank is placed in, in 20rpm/min
Middle mixing 15min, fluidized bed granulation obtain suspension mix granule formulation.
Dissolution determination:
The granule and original for taking above-described embodiment one to be prepared grind posaconazole (Noxafil), by Chinese Pharmacopoeia 2015
Year second annex dissolution method of version, using paddle method, 50rpm/min, 37 ± 0.5 DEG C of temperature, with 1.0 hydrochloride buffer of PH
Solution is operated according to methods as dissolution medium, 10min, 20min, 30min, 45min, and 10ml solution 0.45um is extracted when 60min
Miillpore filter, filtration, precision measure 2ml subsequent filtrate into the volumetric flask of 50ml, constant volume, according to spectrophotometry, in wavelength
Its absorbance is measured at 262nm, and it is as shown in table 1 to calculate its dissolution rate.
Table 1:
| Preparation | 10min | 20min | 30min | 45min | 60min |
| Ethyl cellulose | 21.8 | 32.3 | 41.5 | 51.2 | 63.4 |
| Cholesterol stearic acid | 23.6 | 33.6 | 42.2 | 52.3 | 65.5 |
| Polyacrylic resinⅡ | 24.3 | 34.5 | 43.7 | 54.0 | 61.1 |
| Tripalmitin | 19.7 | 30.2 | 40.3 | 51.6 | 62.7 |
| Noxafil | 9.3% | 20.2% | 28.6% | 35.4% | 40.3% |
In terms of result, the dissolution rate of posaconazole formulations made from the preparation method according to embodiment one is obviously increased.
Internal pharmacokinetics experiment:
Experimental rat 30 (being averagely about 200g) is taken, 5 groups is divided into, every group 6, gavages embodiment one respectively and be made
Posaconazole formulations and original grind posaconazole (Noxafil), be administered by 40mg/Kg dosage, respectively in 30min, 60min,
90min, 120min, 180min, 240min, 300min hind leg take medicine 0.5ml, EtOH Sonicate 20min, and centrifugation takes supernatant
20ul sample introduction HPLC detection level, pharmacokinetic parameters such as following table indicate.
Posaconazole formulations and original grind posaconazole (Noxafil) in mouse Internal pharmacokinetics parameter, as shown in table 2.
Table 2:
| Ethyl cellulose | 483 | 712.4 | 3.5 |
| Sour cholesterol is stearic | 475 | 698.3 | 3.7 |
| Polyacrylic resinⅡ | 490 | 703.3 | 3.4 |
| Tripalmitin | 487 | 710.1 | 4.0 |
| Noxafil | 434 | 418.6 | 6.2 |
Upper table the result shows that, the dissolution rate of posaconazole formulations made from the preparation method according to embodiment one obviously increases
Add.
Disclosed oral posaconazole preparation and preparation method thereof has simple production process, and at low cost is excellent
Point.The present invention improves the solubility and dissolution rate of posaconazole, and existing to improve the bioavilability of posaconazole
It is preferable that dosage form compares curative effect.
The series of detailed descriptions listed above only for feasible embodiment of the invention specifically
Protection scope bright, that they are not intended to limit the invention, it is all without departing from equivalent implementations made by technical spirit of the present invention
Or change should all be included in the protection scope of the present invention.
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Benefit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent elements of the claims
Variation is included within the present invention.
In addition, it should be understood that although this specification is described in terms of embodiments, but not each embodiment is only wrapped
Containing an independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should
It considers the specification as a whole, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
The other embodiments being understood that.
Claims (10)
1. a kind of oral posaconazole preparation, which is characterized in that insoluble with the water for dispersing posaconazole including posaconazole
Property carrier, the mass ratio of the posaconazole and water insoluble carrier is 1:0.5-5.
2. oral posaconazole preparation according to claim 1, which is characterized in that the water insoluble carrier is that ethyl is fine
Tie up one of element, cholesterol stearic acid, polyacrylic resins and tripalmitin or two or more arbitrary proportions
Mixture.
3. oral posaconazole preparation according to claim 2, which is characterized in that the water insoluble carrier is that ethyl is fine
The mass ratio of dimension element, the posaconazole and ethyl cellulose is 1:1.3~2.0.
4. oral posaconazole preparation according to claim 1-3, which is characterized in that the oral preparation may be used also
Pharmaceutically acceptable excipients are added.
5. oral posaconazole preparation according to claim 4, which is characterized in that the excipients are suspending agent, sweet taste
The mixture of one of agent and binder or two or more arbitrary proportions.
6. a kind of preparation method of oral posaconazole preparation, which comprises the following steps:
Step (1): water insoluble carrier is dissolved in ethyl alcohol or ethyl acetate, obtains the water that mass concentration is 15%~35%
Insoluble carrier；
Step (2): dispersing posaconazole in the water insoluble carrier made from step (1), makes posaconazole and water not
The mass ratio of solubleness carrier is 1:0.5~5, is stirred, and volatilizees and is evaporated after homogeneous dispersion, dry, obtains the dispersion of posaconazole solid
Body；
Step (3): pharmaceutically acceptable excipients are added into the posaconazole solid dispersions of step (2), particle is made
Agent.
7. preparation method according to claim 6, which is characterized in that the water insoluble carrier in the step (1) is second
One of base cellulose, cholesterol stearic acid, polyacrylic resins and tripalmitin or two or more any ratios
The mixture of example.
8. preparation method according to claim 7, which is characterized in that the water insoluble carrier is ethyl cellulose, institute
The mass ratio for stating posaconazole and ethyl cellulose is 1:1.3~2.0.
9. preparation method according to claim 6, which is characterized in that the temperature that the volatilization in the step (2) is evaporated is
65 DEG C~95 DEG C, the time being evaporated of volatilizing is 1.5h~3.5h.
10. preparation method according to claim 6, which is characterized in that the drying condition in the step (2) is dry for vacuum
Dry or fluidized bed drying.
Priority Applications (1)
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150231081A1 (en) * | 2014-02-20 | 2015-08-20 | Cadila Healthcare Limited | Delayed release posaconazole tablets |
| CN104971045A (en) * | 2014-04-11 | 2015-10-14 | 上海宣泰医药科技有限公司 | Posaconazole medicine composition, preparation method and medicine preparation thereof |
| CN108125921A (en) * | 2017-12-28 | 2018-06-08 | 广州玻思韬控释药业有限公司 | A kind of posaconazole solid dispersion composition that can inhibit crystallization and be precipitated and preparation method thereof |
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2018
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Patent Citations (3)
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|---|---|---|---|---|
| US20150231081A1 (en) * | 2014-02-20 | 2015-08-20 | Cadila Healthcare Limited | Delayed release posaconazole tablets |
| CN104971045A (en) * | 2014-04-11 | 2015-10-14 | 上海宣泰医药科技有限公司 | Posaconazole medicine composition, preparation method and medicine preparation thereof |
| CN108125921A (en) * | 2017-12-28 | 2018-06-08 | 广州玻思韬控释药业有限公司 | A kind of posaconazole solid dispersion composition that can inhibit crystallization and be precipitated and preparation method thereof |
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| Title |
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| 郝继红等: "泊沙康唑干混悬剂的制备及稳定性研究", 《北方药学》 * |
| 高涛等: "《药剂学》", 31 May 2017, 延边大学出版社 * |
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