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使用SLN和NLC作为咪唑类抗真菌药物的局部微粒载体。

The use of SLN and NLC as topical particulate carriers for imidazole antifungal agents.

作者信息

Souto E B, Müller R H

机构信息

Department of Pharmaceutics, Biopharmaceutics and Biotechnology, Free University of Berlin, Germany.

出版信息

Pharmazie. 2006 May;61(5):431-7.

Abstract

Two different imidazole antifungal agents have been used as model drugs to be incorporated into solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), once they are very well established as anti-mycotics for the treatment of topical fungal infections. Because of the high mucoadhesive properties and the strong in situ gelling properties of polyacrylic acid polymers, hydrogels prepared with those macromolecules might be a promising vehicle for imidazole-loaded lipid nanoparticles, such as the above-mentioned SLN and NLC. Thus, in this study Carbopol 934 has been selected for the preparation of semi-solid formulations based on SLN and NLC. Formulations have been stored at three different temperatures before and after particle incorporation into polyacrylate hydrogels. The particle size and the chemical stability of incorporated model drugs have been monitored by HPLC analysis for two years. On the day of production 91.7% and 98.7% of clotrimazole, but only 62.1% and 70.3% of ketoconazole have been recovered from SLN and NLC, respectively. More than 95% of clotrimazole but less than 30% of ketoconazole were detected in the developed formulations after a shelf life of two years. Those values showed to be higher than those obtained with reference emulsions of similar composition and droplet sizes. By rheological measurements a pseudoplastic behaviour with thixotropic properties has been characterized for all semi-solid systems.

摘要

两种不同的咪唑类抗真菌剂已被用作模型药物,用于制备固体脂质纳米粒(SLN)和纳米结构脂质载体(NLC),因为它们作为抗真菌药物用于治疗局部真菌感染已得到充分认可。由于聚丙烯酸聚合物具有高粘膜粘附性和强原位凝胶化特性,用这些大分子制备的水凝胶可能是负载咪唑类脂质纳米粒(如上述的SLN和NLC)的一种有前景的载体。因此,在本研究中,选择了卡波姆934来制备基于SLN和NLC的半固体制剂。在将颗粒掺入聚丙烯酸水凝胶之前和之后,制剂分别在三种不同温度下储存。通过高效液相色谱分析监测掺入的模型药物的粒径和化学稳定性,为期两年。在生产当天,从SLN和NLC中分别回收了91.7%和98.7%的克霉唑,但酮康唑的回收率分别仅为62.1%和70.3%。在两年的保质期后,在开发的制剂中检测到超过95%的克霉唑,但酮康唑不到30%。这些值高于具有相似组成和液滴尺寸的参考乳液所获得的值。通过流变学测量,所有半固体系统均表现出具有触变性的假塑性行为。

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