CN104721827A - Insoluble antifungal medicament solid dispersion and preparation method thereof - Google Patents
Insoluble antifungal medicament solid dispersion and preparation method thereof Download PDFInfo
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Abstract
The invention relates to the field of pharmaceutical preparation, and in particular to a posaconazole solid dispersion and a preparation method of the solid dispersion. More specifically, the invention provides a posaconazole solid dispersion composed of posaconazole and hydroxy propyl methyl cellulose (HPMC) in the weight ratio of 1:0.5-20. Preferably, HPMC contains 4%-12% (wt) of hydroxypropyl group, and 19.0%-30.0% (wt) of methoxyl group, and has viscosity of 5-15 mpa.s at 20 DEG C in 2% (wt) aqueous solution, more preferably. The posaconazole solid dispersion provided by the invention can significantly increase the solubility of the posaconazole in gastrointestinal tract and improve the bioavailability. The solid dispersion provided by the invention is simple for preparation of medicinal preparation and facilitates the guarantee of the quality of the medicament preparation.
Description
Technical field
The invention belongs to pharmaceutical technology sectors, be specifically related to a kind of slightly solubility antifungal drug solid dispersion and preparation method thereof, more specifically, relate to a kind of solid dispersion of posaconazole and the preparation method of this solid dispersion and medicinal application.
Background technology
Posaconazole (posaconazole, commodity are called Noxafil) be the triazole antifungal agent of a kind of wide spectrum that JIUYUE in 2006 is ratified by U.S. FDA on the 15th, for the fungal infection caused by refractory disease or other drug drug resistance (as aspergillosis, tulase disease and fusaridiosis etc.), this medicine develops listing by Schering-Plough company of the U.S., it is a kind of new chemical molecular entity, first antibacterials for preventing to be caused by aggressive aspergillosis pathological changes ratified by FDA, belong to highly lipophilic antifungal agent, identical with other azole antibacterials, this medicine is also by being combined with the haemachrome cofactor of lanosterol 14 α-demethylase (CYP51 or Erg11p) active site, the biosynthesis of Antifungi ergosterol, destroy the formation of cell membrane and integrity and play antibacterial action.Posaconazole overcomes the problems such as the low and drug resistance of first generation triazole type medicine narrow antimicrobial spectrum, bioavailability, its antifungal effect has all been proved the activity with wide spectrum with external in vivo, to candidiasis, various aspergillosis and other common all have larger activity with non-common pathomycete.
Suspension containing the posaconazole (40 mg/ml) of crystal form is especially approved for oral medication invasive fungal infection as Noxafil at US and European, such as treat oropharangyl candidiasis, comprise the infection of other azole antifungal agent of tolerance treatment, likely there is these patients infected with prevention due to sever immune disappearance with as prophylactic treatment, as there is hematopoietic stem cell transplantation (HSCT) receptor of graft versus host disease (GVHD) or having from the fungal infection in the hematologic malignancies patient of the long-term neutropenia of chemotherapy.
The supply comprising the solid composite of posaconazole being applicable to prepare oral dosage form is limited by poor solubility and the alkalescence of posaconazole free alkali compound so far.Posaconazole is solvable at a low ph.Such as, in the environment of stomach (about pH 1), posaconazole free alkali has the dissolubility of about 0.8 mg/ml.But, when being dissolved in the posaconazole in gastric juice and arriving intestinal environment (usual acidity is less than about pH6.4), the posaconazole the dissolved precipitation of significant quantity, thus hinder the absorption in intestinal.Determine, be in the environment of about pH 6.4 or more alkaline at pH, the dissolubility of posaconazole free alkali is less than about 1 mcg/ml.
Solid dispersion (SD) refers to a kind of disperse system existed in solid form being highly dispersed in by medicine and being formed in solid carrier.The stripping of conventional acceleration lipotropy and insoluble drug and the method for its bioavailability of increase.The existence of carrier not only prevents the gathering of the single drug particles with higher solid-liquid surface tension/stick and the microenvironment that the dissolubility constructing its Chinese medicine is higher, thus increases the dissolubility of insoluble drug.Although pharmacy literature often reports the application of solid dispersion, but due to these structure physical instabilities (aging action), between the storage life, be separated, crystalline growth or unformed (metastable state) transform to crystalline state, all inevitably cause dissolubility and dissolution rate to reduce.Therefore, for the suitable carrier of concrete medicament selection to prevent recrystallize extremely important.
Summary of the invention
The object of the invention is to overcome antifungal drug in triazole class posaconazole in prior art poorly soluble at small intestinal, the shortcoming that bioavailability is low, a kind of novel posaconazole solid dispersion and preparation method thereof and its medicinal application are provided.
For foregoing invention object, the invention provides following technical scheme:
The invention provides a kind of posaconazole solid dispersion, it is characterized in that, be made up of posaconazole and hypromellose (HPMC).
In posaconazole solid dispersion provided by the invention, wherein the weight ratio of posaconazole and hydroxypropyl emthylcellulose is 1:0.5 ~ 20, the weight ratio of preferred posaconazole and HPMC is 1:11 ~ 20 or 1:1 ~ 5, and further, the weight ratio of preferred posaconazole and HPMC is 1:1.5.
When the weight ratio of posaconazole and HPMC in solid dispersion of the present invention is lower than 1:0.5, find that posaconazole can not be dispersed in carrier HPMC completely, and when the weight ratio of posaconazole and HPMC more than 1:20 time, prepare solid dispersion surface viscosity to increase, and during by further for prepared solid dispersion molding, when the posaconazole containing effective dose, make the tablet sizes prepared excessive or be difficult to load into capsule.Therefore, determine posaconazole and HPMC weight ratio be 1:0.5 ~ 20.
Wherein, the HPMC used in the present invention contains enough methoxyl groups and hydroxypropyl to ensure that it has good water solublity, and described HPMC is preferably 4% ~ 12%(wt containing hydroxypropyl content), methoxyl content is 19.0% ~ 30.0%(wt).Further, in preferably described HPMC, methoxyl content is 28% ~ 30%(wt), hydroxypropyl content is 7% ~ 12%(wt).
Hydroxypropyl emthylcellulose another name is hypromellose, HPMC, according to the specification defining four kinds of HPMC in methoxyl group American Pharmacopeia (USP32) different from the content of hydroxypropyl, that is: HPMC1828, HPMC2208, HPMC2906 and HPMC2910.Wherein, in HPMC1828, HPMC2208, HPMC2906 and HPMC2910, methoxyl content is respectively 16.5 – 20.0%, 19.0 – 24.0%, 27.0 – 30.0%, 28.0 – 30.0%, and hydroxypropyl content is respectively 23.0 – 32.0%, 4.0 – 12.0%, 4.0 – 7.5%, 7.0 – 12.0%.
Specification is the hydroxypropyl content of HPMC2208, HPMC2906 and HPMC2910 is 4% ~ 12%(wt), methoxyl content is 19.0% ~ 30.0%(wt), preferably as HPMC of the present invention; The preferred HPMC2910 of further HPMC of the present invention.
HPMC molecular size range also has certain influence to the stripping curve of solid dispersion and the physical property of medicine, for obtaining desirable drug release patterns, in immediate release drug, and preferred low-molecular-weight HPMC; And in sustained and controlled release medicament the HPMC of preferred high component.Water-soluble cellulose ether, the apparent viscosity of described cellulose ether in 20 DEG C of aqueous solutions that the molecular weight of such as HPMC commonly uses 2% weight represents.Be applicable to the HPMC that the preferred viscosity of HPMC of the present invention is 1 ~ 100 mPa.s, further preferably viscosity is the HPMC of 3 ~ 15 mPa.s, further preferably selects viscosity to be the HPMC of 5 mPa.s.What preferred viscosity was HPMC described in 5 mPa.s is can the specification that obtains of commodity be HPMC2910, and viscosity is the HPMC of 5 mPa.s.
The particle size distribution of HPMC is that another affects the factor of the quality of solid dispersion, and HPMC preferred size of the present invention is that 100 order percent of pass are greater than 98.5%, and 80 order percent of pass are greater than 100%.
On the other hand, present invention also offers a kind of preparation method of posaconazole solid dispersion, comprise the following steps:
The HPMC that posaconazole mixes with one or more is done fusion, forms uniform admixture; Described admixture is heated under the temperature pre-set (such as 70 ~ 280 DEG C), mixing speed condition, obtains uniform molten mass; Described molten mass is extruded by head nib, cooling, pulverize and obtain posaconazole solid dispersion.
Posaconazole solid dispersion provided by the present invention can be melt extruded method and prepared by above-mentioned, also can according to the customary preparation methods of the known solid dispersion of those skilled in the art of the present technique as hot pressing mixing method, spray drying method, coprecipitation, freeze-drying, polishing and supercritical methanol technology etc. prepare altogether.
Illustrative, the step adopting freeze-drying to prepare posaconazole solid dispersion of the present invention comprises:
Posaconazole and HPMC are dissolved in organic solvent respectively; Two kinds of solution mixtures are stirred 2h, obtain settled solution, filter, freezing, lyophilizing, dissolved or white solid powder in molecular dispersion HPMC.
Wherein said organic solvent is the acidic aqueous solution of methanol, ethanol or isopropyl alcohol, and its concentration is 85% ~ 100%; Acid is concentrated hydrochloric acid, sulphuric acid or glacial acetic acid, preferred concentrated hydrochloric acid; Organic solvent and the sour preferred 10:1(v/v of consumption); Described organic solvent can also be dichloromethane.Described freezing that liquid nitrogen can be used to carry out is freezing, and cooling time is about 48h.
When posaconazole solid dispersion of the present invention is used for the treatment of as active component, directly can give the posaconazole solid dispersion that patient is simple, as oral in given patient by posaconazole solid dispersion with the form of powder or direct fill capsulae vacuus.In order to ensure the multiformity of medicine quality and pharmaceutical dosage form, also posaconazole solid dispersion of the present invention can be mixed with one or more pharmaceutically acceptable auxiliaries and this mixture is pressed into Tabules and maybe give patient by the form that this mixture incapsulates and take, in the pharmaceutical preparation wherein prepared at solid dispersion and pharmaceutic adjuvant, posaconazole content is 100 ~ 500mg, and preferred posaconazole content is 200mg.
Pharmaceutic adjuvant of the present invention refers to the filler, binding agent, disintegrating agent, lubricant, coloring agent, flavoring agent, pH adjusting agent etc. that carry out required interpolation when preparation is produced, the interpolation of these excipient substances belongs to the routine techniques means of those skilled in the art, and addition belongs to the scope not affecting effect of the present invention.
Described filler comprises lactose, starch, microcrystalline Cellulose, dextrin, pregelatinized Starch etc.; Described binding agent comprises hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, ethyl cellulose, starch slurry, Polyethylene Glycol, polyvidone etc.; Described disintegrating agent comprises the hydroxypropyl cellulose, polyvinylpolypyrrolidone, carboxymethylstach sodium, gas-producing disintegrant etc. of low replacement; Described lubricant comprises magnesium stearate, Pulvis Talci, silicon dioxide, micropowder silica gel, Polyethylene Glycol etc.; Described coloring agent comprises that beet red, lac are red, red pigment of cowberry, cassava leaf meal, Fructus Citri Limoniae nucleic etc.; Described flavoring agent comprises maltose alcohol, steviosin, fructose, Fructus Citri tangerinae essence etc.; Described pH adjusting agent comprises phosphate buffer, citric acid, sodium citrate, acetate buffer, sodium hydroxide, dilute hydrochloric acid, sodium carbonate etc.; Two outer that also can comprise other routines, appropriate additives, as wetting agent or emulsifying agent etc.
Pharmaceutical composition of the present invention is semi-finished product, preparation, preparation compositions containing active constituents of medicine and pharmaceutic adjuvant composition, and the preparation formulation usually can produced comprises tablet, capsule, granule, powder, suspensoid etc.Solid preparation can also pass through coat film coating, to cover the relevant taste of medicine or to improve product stability further.Pharmaceutical composition of the present invention is preferably oral formulations, described oral formulations preferred tablet or capsule.Film coating on tablet further contributes to being swallowed.
As known in the art, Tablet blends can before tableting with dry granulation or wet granulation.Flaking method itself is standard, and can use the tablet of the suitable character of conventional tablet pressure initiation.Tablet of the present invention can with improved taste, conveniently be swallowed by film coating further, and obtains good outward appearance.Suitable thin film coating material is known in the art, preferred HPMC, further preferred HPMC 2910 5mPa.s.Other thin film coating material comprises HPMC and acrylate-methyl olefin(e) acid ester copolymer, also may be used for the present invention.
Posaconazole solid dispersion of the present invention, it is the pressed powder that posaconazole is highly dispersed in HPMC, adopt the carrier of HPMC as solid dispersion of low-viscosity, good water solubility, significantly increase posaconazole in gastrointestinal dissolubility, thus overcome the low defect of the bioavailability that causes because posaconazole dissolubility is low.Adopt posaconazole and HPMC with the ratio of 1:0.5 ~ 20, especially the solid dispersion for preparing with the ratio of 1:1.5 of posaconazole and HPMC 2910 5mPa.s, stable in properties, not easily aging, significantly improve in gastrointestinal tract dissolubility.
Easy and be easy to ensure the quality of pharmaceutical preparation by solid dispersion preparation pharmaceutical preparation preparation method provided by the present invention, good with the tablet compactibility of solid dispersion preparation provided by the invention, under guarantee posaconazole effective dose condition, tablet sizes is suitable for.Compared with the oral posaconazole suspensoid (trade name: Noxafil) of listing, solid dispersion provided by the present invention or aobvious high, the good stability of pharmaceutical composition dissolution rate, and significantly improve the bioavailability of posaconazole.
Following drawings and Examples further illustrate other aspects and advantages of the present invention.
Accompanying drawing explanation
X-the ray powder diffraction of the posaconazole solid dispersion that Fig. 1 display is prepared according to embodiment 2 method, collection of illustrative plates shows, and posaconazole exists with unformed state.
Fig. 2 shows the posaconazole solid dispersion prepared according to the method for embodiment 1,2,3 and the Dissolution of Tablet curve prepared according to embodiment 7.
Specific embodiment
In order to make technical problem solved by the invention, technical scheme and beneficial effect clearly understand, below in conjunction with specific embodiment, the present invention will be further described.
HPMC buys in Dow Chemical company.Other reagent and adjuvant are common agents and adjuvant if no special instructions, commercially available acquisition.
embodiment 1containing the preparation of the solid dispersion of posaconazole and HPMC
100g posaconazole is dissolved in 500ml methanol, the hydroxypropyl methylcellulose (HPMC 2208 15mPa.s) of 1100g is fully dissolved in 2000g dichloromethane, by two kinds of solution mixing, stir, spray dryer (B-191 Mini Spray-Drier, Buchi Co., Switzerland) is adopted to spray to posaconazole and HPMC mixed solution, be scattered in solid dispersion in HPMC to form posaconazole, generate white armorphous powder.Posaconazole: HPMC weight ratio is 1:11.
embodiment 2containing the preparation of the solid dispersion of posaconazole and HPMC
Preparation method: 100g posaconazole is dissolved in 500ml methanol, then, the hydroxypropyl methylcellulose (HPMC 2906 15mPa.s) of 150g is fully dissolved in 300ml dichloromethane, by two kinds of solution mixing, stir, adopt spray dryer (B-191 Mini Spray-Drier, Buchi Co., Switzerland) mixed solution of posaconazole and HPMC is sprayed, then 22 DEG C of pulverizing are cooled to, after crossing 80 mesh sieves, solid dispersion in HPMC is scattered in form posaconazole, generate white armorphous powder (Fig. 1 is the X-powder diffraction spectrum of posaconazole solid dispersion).The weight ratio of posaconazole: HPMC is 1:1.5.
embodiment 3containing the preparation of posaconazole and HPMC solid dispersion
By posaconazole and HPMC(HPMC 2910 5mPa.s) even with the weight ratio mixture of 33.3:166.7, then Ke Bei Long Keya company of parallel dual-screw extruding machine TE-20(Germany is adopted), set the temperature of each section to head, after balance 20Min, setting screw speed is 25r/min, the physical mixture 200g of above-mentioned posaconazole and HPMC is dropped in loading hopper, after 1min, material head nib is extruded with strip, by extrudate access on glass plate, after placing 4h under being cooled to room temperature condition, pulverize, cross 80 mesh sieves, obtain white powder.The weight ratio of posaconazole: HPMC is 1:5.
embodiment 4containing the preparation of the solid dispersion of posaconazole and HPMC
100g posaconazole is dissolved in 500ml methanol, then, HMPC(HPMC 2910 5mPa.s by 50g) in 150ml dichloromethane, by two kinds of solution mixing, stir, through drying under reduced pressure except desolventizing, then dry, be cooled to 25 DEG C of pulverizing, after crossing 80 mesh sieves, obtain posaconazole solid dispersion.The weight ratio of posaconazole: HPMC is 1:0.5.
embodiment 5containing the preparation of the solid dispersion of posaconazole and HPMC
100g posaconazole is dissolved in 500ml methanol, then, HMPC(HPMC 2910 5mPa.s by 100g) and 300ml dichloromethane in, by the mixing of two kinds of solution, stir, adopt spray dryer (B-191 Mini Spray-Drier, Buchi Co., Switzerland) mixed solution of posaconazole and HPMC is sprayed, be then cooled to 22 DEG C of pulverizing, after crossing 80 mesh sieves, be scattered in solid dispersion in HPMC to form posaconazole.The weight ratio of posaconazole: HPMC is 1:1.
embodiment 6containing the preparation of posaconazole and HPMC solid dispersion
By posaconazole and HPMC(HPMC 2910 5mPa.s) mix homogeneously with the weight ratio of 10:200, then Ke Bei Long Keya company of parallel dual-screw extruding machine TE-20(Germany is adopted), set the temperature of each section to head, after balance 20Min, setting screw speed is 25r/min, the physical mixture 210g of above-mentioned posaconazole and HPMC is dropped in loading hopper, after 1min, material head nib is extruded with strip, by extrudate access on glass plate, after placing 4h under being cooled to room temperature condition, pulverize, cross 80 mesh sieves, obtain white powder.The weight ratio of posaconazole: HPMC is 1:20.
embodiment 7the preparation of tablet,
Posaconazole solid dispersion obtained for embodiment 2 and colloidal silica are passed through 30 object mesh screens sieve and fully mix.Then, add other components except magnesium stearate and Talcum in lower list 1 wherein, mixing, dry also pelletize, obtains the granule of size uniform by 25 order mesh screens.Subsequently, add magnesium stearate and Talcum also abundant mix homogeneously wherein, mixture is made tablet.
Table 1:
Also above-mentioned tablet can be mixed with suitable pharmaceutical coating material according to those skilled in the art of the present technique's known method, adopt tablet-coating machine to be prepared into film coating, sweet tablet or enteric coated tablet.
Illustrative, such as, by the tablet of above-mentioned preparation, use the suspension comprising following ingredients (percentage by weight) to carry out thin film coated: HPMC 2910 5mPa.s(8.0%), propylene glycol (2.0%), Pulvis Talci (1.5%) titanium dioxide (2.5%).HPMC 2910 5mPa.s to be joined in purified water and mixing until disperse completely.Standing solution knows clarification, adds mixed with propylene glycol to even.Pulvis Talci and titanium dioxide to be added in solution and mixture to evenly.The tablet of above-mentioned preparation is placed in coating pan, by suspension spray in core.The heavy 920g of average sheet.
embodiment 8the preparation of capsule
The solid dispersion prepared by above-described embodiment 5 mixes by ratio with excipient substance listed by lower list 2, according to the customary preparation methods of capsule, prepares capsule.
Table 2:
test example 1solid dispersion Their Dissolution Test in vitro
The posaconazole solid dispersion prepared according to the method for embodiment 1,2,3 and the tablet prepared according to embodiment 7, as test group a;
With commercially available oral posaconazole suspensoid (Noxafil) for matched group b.
Get matched group a sample, according to dissolution detection method (China's coastal port two annex XC the 3rd method), employing slurry processes measures, with phosphate buffer (pH6.8) 250ml for dissolution medium, rotating speed is 75 turns per minute, dissolution fluid 10ml is respectively taken out 5,10,15,20,30,45,60,80 minutes time, and fluid infusion 10ml, with 0.8 μm of filtering with microporous membrane, add stripping medium to scale, shake up, measure with ultraviolet visible spectrophotometry, measure trap respectively at the wavelength place of 254nm; It is appropriate that another precision takes posaconazole reference substance, first dissolves with absolute methanol, adds to state solvent dilution and make solution containing 25 μ g in every 1ml, is measured in the same method trap, often organizes survey 3 groups of data, obtain the meansigma methods of dissolution.Result of the test is shown in accompanying drawing 2, and vertical coordinate is posaconazole Cumulative release amount (%).
As shown in Figure 2, the posaconazole solid dispersion dissolution prepared by the inventive method, in 45 minutes, Cumulative release amount is all more than 80%, wherein the posaconazole solid dispersion prepared of the method for embodiment 2 is best, in 45 minutes, the Cumulative release amount of posaconazole reaches 91%, is significantly higher than reference substance.
test example 2bioavailability study in body
Bioavailability may be defined as the speed and degree that active pharmaceutical ingredient or treatment part absorb from the dosage form taken to the blood circulation being rapidly absorbed into system relative to standard substance or reference substance.C
maxvalue is defined as the maximum plasma concentration (that is: peak value) of the antifungal compound recorded.AUC
(tf)for from the zero-time to the lower area of blood concentration-time curve of final measurable sample time, calculated by trapezoidal area method, and calculate infinite value (I) by company below: AUC (I)=AUC
(tf)* C
(tf)/ K, wherein C
(tf)it is the estimated concentration at time tf calculated with linear regression.
For measuring the bioavailability of the solid dispersion of posaconazole provided by the invention and the pharmaceutical preparation containing it, test as follows:
Tablet prepared by the posaconazole solid dispersion prepared according to the method for embodiment 2 and embodiment 7 is as mensuration group a.
With commercially available oral posaconazole suspensoid (Noxafil) for matched group b.
After 24 body weight being the male Sprague-Dawly Rat Fast 12h in 14 or 15 week age of about 300g, it is divided into 3 groups at random, often group is containing 8 rats.
To three groups of rats respectively gavage give the embodiment of the present invention 2 prepare solid dispersion, embodiment 7 prepare tablet and Noxafil oral suspensions, dosage is 20mg posaconazole/kg rat body weight.Upon administration 0,2,4,6,8,10,12,24,48,72 and 96h, get blood by eye socket, then therefrom isolate serum, process, measure posaconazole content.
Result of the test find tablet prepared by the solid dispersion prepared by the embodiment of the present invention 3 and embodiment 7 upon administration 3.6h reach maximum plasma concentration, compared with commercially available oral posaconazole suspensoid Noxafil, solid dispersion provided by the invention and tablet bioavailability are significantly increased, the solid dispersion C of wherein embodiment 2 preparation
max217% and 211% is improve respectively compared with commercially available oral posaconazole suspensoid Noxafil with AUC.Embodiment 7 prepare tablet compared with commercially available oral posaconazole suspensoid Noxafil, C
max198% and 192% is improved respectively with AUC.
The solid dispersion prepared according to the method for embodiment 4,5,6 carries out bioavailability study in similar Dissolution Rate Testing and body, obtains and above-mentioned substantially identical result of the test.
Can draw from above-mentioned several groups of result of the tests, posaconazole solid dispersion prepared by technology provided by the present invention or preparation all have good performance in dissolution rate, bioavailability.
It should be noted that and the foregoing is only preferred embodiment of the present invention, be not limited to the present invention, all any amendments done within the spirit and principles in the present invention, equivalent replacement and improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. a posaconazole solid dispersion, is characterized in that, is made up of posaconazole and hydroxypropyl emthylcellulose.
2. posaconazole solid dispersion as claimed in claim 1, it is characterized in that, the weight ratio of posaconazole and hydroxypropyl emthylcellulose is 1:0.5 ~ 20.
3. posaconazole solid dispersion as claimed in claim 1, it is characterized in that, the weight ratio of posaconazole and hydroxypropyl emthylcellulose is 1:11 ~ 20.
4. posaconazole solid dispersion as claimed in claim 1, it is characterized in that, the weight ratio of posaconazole and hydroxypropyl emthylcellulose is 1:1 ~ 5.
5. posaconazole solid dispersion as claimed in claim 1, it is characterized in that, the weight ratio of posaconazole and hydroxypropyl emthylcellulose is 1:1.5.
6. the posaconazole solid dispersion as described in as arbitrary in claim 1 ~ 5, it is characterized in that, in described hydroxypropyl emthylcellulose, hydroxypropyl content is 4% ~ 12%(wt), methoxyl content is 19.0% ~ 30.0%(wt).
7. posaconazole solid dispersion as claimed in claim 6, is characterized in that, described hydroxypropyl emthylcellulose at 20 DEG C, 2%(wt) viscosity in aqueous solution is 5 ~ 15 mpa.s.
8. a pharmaceutical composition, is characterized in that, comprises posaconazole solid dispersion according to claim 1, and at least one pharmaceutically acceptable auxiliaries.
9. pharmaceutical composition as claimed in claim 8, it is characterized in that, described pharmaceutical composition is tablet or capsule.
10. described in a claim 1, posaconazole solid dispersion is treating and/or preventing the purposes in fungal infections in mannals.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017032908A1 (en) | 2016-07-08 | 2017-03-02 | Synthon B.V. | Pharmaceutical composition comprising amorphous posaconazole |
| CN108066289A (en) * | 2017-12-28 | 2018-05-25 | 广州玻思韬控释药业有限公司 | A kind of posaconazole solid dispersions and preparation method thereof and posaconazole enteric coated preparations |
| CN110960499A (en) * | 2019-12-31 | 2020-04-07 | 卓和药业集团有限公司 | Posaconazole gastric floating tablet and preparation method thereof |
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| CN1209740A (en) * | 1996-05-20 | 1999-03-03 | 詹森药业有限公司 | Anti-fungus composition with improved biological utilization ratio |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017032908A1 (en) | 2016-07-08 | 2017-03-02 | Synthon B.V. | Pharmaceutical composition comprising amorphous posaconazole |
| CN108066289A (en) * | 2017-12-28 | 2018-05-25 | 广州玻思韬控释药业有限公司 | A kind of posaconazole solid dispersions and preparation method thereof and posaconazole enteric coated preparations |
| CN110960499A (en) * | 2019-12-31 | 2020-04-07 | 卓和药业集团有限公司 | Posaconazole gastric floating tablet and preparation method thereof |
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