热熔挤出技术制备伊曲康唑固体分散体及体外溶出考察

以羟丙甲纤维素(HPMC E5)为分散载体,利用热熔挤出技术制备难溶性药物伊曲康唑固体分散体,并探究不同挤出工艺参数和增塑剂1,2-丙二醇(PG)含量对固体分散体溶出度的影响。结果表明,二次挤出制得的固体分散体中药物的溶出率大于直接挤出的固体分散体,且二者均明显大于物理混合物。使用PG作增塑剂后伊曲康唑固体分散体的溶出率得到了显著提高,当PG用量较高(10%)时,固体分散体在0.1 mol/L盐酸介质中的溶出率可达到93%。本研究可以为热熔挤出的工艺开发提供更多的思路,同时为进一步制备高规格(200 mg)伊曲康唑片剂提供帮助。

Preparation and Dissolution of Itraconazole Solid Dispersion by Hot Melt Extrusion Method

In this study, hydroxypropyl methylcellulose(HPMC) E5 was used as a dispersion carrier to prepare a solid dispersion of the poorly soluble drug itraconazole by hot melt extrusion technique, and the effects of different extrusion process parameters and amount of plasticizer(1,2-propanediol, PG) on the dissolution of different solid dispersions were investigated. The results showed that the dissolution of the secondarily extruded solid dispersion was higher than that of the directly extruded solid dispersion, and both were significantly higher than the physical mixture(PM). The dissolution of the itraconazole solid dispersion was significantly improved by adding PG as a plasticizer. When the amount of PG added was increased to 10%, the dissolution of the solid dispersion rose to 93% in 0.1 mol/L hydrochloric acid. This study could provide more ideas for the application of hot melt extrusion process in improving dissolution of poorly soluble drug, and the development of high dosage itraconazole tablets(200 mg).