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目的研究二氯甲烷-乙醇混合溶剂组分比对喷雾干燥制备伊曲康唑固体分散体物理性质的影响。方法采用HPLC测定室温下伊曲康唑在不同体积比的二氯甲烷-乙醇混合溶剂中的平衡溶解度。以PVP VA64为载体,体积比分别为100︰0、90︰10、70︰30、50︰50的二氯甲烷-乙醇混合液为溶剂,采用喷雾干燥法制备伊曲康唑固体分散体,通过扫描电镜、差示扫描量热法、接触角测定仪和体外溶出试验对制得的固体分散体进行表征。采用差示扫描量热法考察固体分散体在90℃放置48,96,192 h后的物理稳定性。结果伊曲康唑溶解度的大小取决于二氯甲烷-乙醇混合溶剂的组成,在不同体积比的二氯甲烷-乙醇混合溶剂中的溶解度差别很大。喷雾干燥制得的4种伊曲康唑固体分散体均为无定形固体分散体,具有单一的玻璃化转变温度、不同的形态和润湿性。体外溶出试验表明相对于原料药,制备得到的4种伊曲康唑固体分散体溶出速率显著提高。90℃高温加速稳定性试验放置后的固体分散体显示不同的物理稳定性。结论二氯甲烷-乙醇混合溶剂组分比会对喷雾干燥制备伊曲康唑固体分散体的物理性质产生显著影响,其原因是由于伊曲康唑在混合溶剂中的溶解度差异会导致药物沉淀析出的时间不同,并进一步影响药物在固体分散体中的分布行为和物理稳定性。
Aim To study the effect of solvent mixture ratio of dichloromethane to ethanol on the physical properties of itraconazole solid dispersion prepared by spray drying. Methods The equilibrium solubility of itraconazole in different volumes of dichloromethane-ethanol mixed solvents was determined by HPLC at room temperature. PVP VA64 as a carrier, respectively, the volume ratio of 100: 0, 90:10, 70:30, 50:50 dichloromethane - ethanol mixture as a solvent spray drying method to prepare itraconazole solid dispersion by Scanning electron microscopy, differential scanning calorimetry, contact angle measurement instrument and in vitro dissolution test of the resulting solid dispersion was characterized. The physical stability of the solid dispersion after 48,96,192 h at 90 ° C was investigated by differential scanning calorimetry. Results Itraconazole solubility depends on the composition of dichloromethane - ethanol mixed solvent, in different volume ratio of dichloromethane - ethanol mixed solvent solubility vary greatly. The four solid forms of itraconazole prepared by spray drying are amorphous solid dispersions with a single glass transition temperature, different morphology and wettability. In vitro dissolution tests showed that compared with the drug substance, the dissolution rate of the four isoconazole solid dispersions prepared was significantly increased. Solid dispersion after 90 ° C high temperature accelerated stability test placement shows different physical stability. CONCLUSIONS: The ratio of dichloromethane to ethanol mixed solvent has a significant effect on the physical properties of itraconazole solid dispersions prepared by spray drying. The reason for this is that the difference in solubility of itraconazole in a mixed solvent leads to precipitation of the drug Of the time, and further affect the drug in the solid dispersion of the distribution behavior and physical stability.