Itraconazole nanocrystals and preparation method and application thereof

A technology of itraconazole and nano-crystallization, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, and medical preparations containing active ingredients. And clinical trials, low bioavailability of preparations and other issues, to achieve the effect of facilitating drug absorption, low cost, and low toxicity

Active Publication Date: 2011-02-02
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above-mentioned itraconazole nanosuspension can improve the dispersibility of the drug, improve the solubility and dissolution rate of the drug to a certain extent, but it is still far from meeting the dissolution and absorption requirements of itraconazole, and cannot pass animal and clinical tests.
[0006] The methods involved in the above documents and patents have improved the in vivo absorption of itraconazole to a certain extent, but there are still many problems, such as the bioavailability of the preparation is still low and is easily affected by ingestion, and the use of organic solvents such as Dichloromethane, significant individual differences in bioavailability, complex preparation process, high cost, etc.

Method used

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  • Itraconazole nanocrystals and preparation method and application thereof
  • Itraconazole nanocrystals and preparation method and application thereof
  • Itraconazole nanocrystals and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Mix and stir 100mg itraconazole with 3ml 3mol / L hydrochloric acid solution and 2ml absolute ethanol as a co-solvent to completely dissolve and form an acid phase;

[0039] Mix the polymer stabilizer 10mg hydroxypropyl methylcellulose (50cp), 0.3g NaOH and 10ml water, stir to dissolve each component completely to form an alkali phase;

[0040] The acid phase is added dropwise to the base phase under stirring at a stirring speed of 50 r / min. After the dropwise addition is completed, the itraconazole nanocrystalline drug suspension is obtained by stirring evenly.

[0041] The effective particle size was measured at 25° C. with a laser particle size analyzer (Nano ZS90, Malvern, UK), and the effective particle size was 309.26 nm.

[0042] Dissolution in vitro: adopt the second method by "Chinese Pharmacopoeia" 2005 edition two appendix X C dissolution assay method, adopt rotating speed per minute 100 turns; Dissolution medium pH=1.38 hydrochloric acid solution (degassing tr...

Embodiment 2

[0045] 100mg of itraconazole, 5ml of 3mol / L hydrochloric acid solution, mixed and stirred to dissolve completely, and then the solution formed by dissolving polymer stabilizer 50mg hydroxypropyl methylcellulose (50cp) in 4ml of distilled water was mixed with it to form an acid phase;

[0046] Polymer stabilizer 50mg hydroxypropyl methylcellulose (50cp), 0.3g NaOH and 10ml water were mixed, stirred to completely dissolve each component to form an alkali phase.

[0047] The acid phase is added dropwise into the alkali phase under stirring condition, and the stirring speed is 500r / min, and the itraconazole nano crystal drug suspension is obtained.

[0048] Measure its effective particle size with a laser particle size analyzer at 25°C, and the effective particle size is 287.9nm. 45min in vitro dissolution up to 91%.

[0049] X-diffraction (X'Pert PRO Dutch Panalytical B.V.) inspection see figure 2 , the results showed that itraconazole nanocrystals were in an amorphous state. ...

Embodiment 3

[0051] 100mg itraconazole, polymer stabilizer 200mg polyvinylpyrrolidone (K30), 2ml 3mol / L hydrochloric acid solution, mixed and stirred to completely dissolve to form an acid phase;

[0052] Surfactant 10mg poloxamer188, 0.3g NaOH mixed with 10ml water, stirred to completely dissolve each component to form an alkali phase.

[0053] The acid phase is added dropwise to the alkali phase under stirring condition, and the stirring speed is 5000r / min, and the itraconazole nano crystal drug suspension is obtained.

[0054] Measure its effective particle size with a laser particle size analyzer at 25°C, and the effective particle size is 296.33nm. 45min in vitro dissolution up to 92%.

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Abstract

The invention provides itraconazole nanocrystals and a preparation method and application thereof. Acid phase in which itraconazole is dissolved is dropwise added into alkaline phase to over-saturate the itraconazole; the itraconazole molecules are aggregated into amorphous nanocrystalline particles in the presence of a high molecular stabilizer to form a stable structure with itraconazole nanocrystals as a core and the high molecular stabilizer as a shell; and both the solubility and the dissolution rate of the itraconazole nanocrystals are greatly improved compared with those of normal itraconazole nanoparticle suspension. A hydrophilic fragment of the high molecular stabilizer, which is extended into the water, improves the hydrophobicity of the surfaces of the itraconazole nanoparticles, so that the high molecular stabilizer is more easily moistened and dissolved; and the high molecular stabilizer serving as the shell enhances the adhesion between the medicament particles and gastrointestinal mucous membrane, is favorable for improving the bioavailability and reduces the influence of a diet state on the bioavailability. The method of the invention has the advantages of no use of toxic solvent, simple preparation process, low cost and easy industrialization.

Description

field of invention [0001] The invention belongs to the field of pharmacy, and specifically relates to nano-pharmaceutical technology, in particular to a preparation method and application of itraconazole nano-crystals. Background of the invention [0002] Itraconazole is a triazole antifungal drug that inhibits the activity of fungal cytochrome P450-dependent sterol 14α-demethylase and prevents the synthesis of ergosterol, an important component of fungal cell membranes, leading to changes in the permeability of fungal cell membranes , so that the activity of enzymes on the cell membrane and the synthesis of chitin are hindered, thereby achieving the purpose of inhibiting fungal proliferation and promoting fungal death. It has few toxic and side effects, strong antibacterial effect, broad-spectrum antibacterial activity and good tolerance. Itraconazole is clinically used to treat fungal infections such as nails, hair and skin; systemic fungal infections in HIV-infected pati...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/48A61K9/10A61K31/496A61K9/46A61K47/38A61P31/10A61K9/16A61K9/20A61K9/14A61K47/32
Inventor 杨祥良牟东升周小顺万江陵陈华兵徐辉碧
Owner HUAZHONG UNIV OF SCI & TECH
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