药物的水溶性差是其生物利用度和药理活性的限制因素。许多方法是已知的,以提高药物的溶解度,其中,物理方法,固体分散体(SD),是应用的。SDs是药物和载体的物理混合物,有时添加表面活性剂,可以通过铣削获得,冷冻研磨,喷雾干燥,或冻干过程。在这项研究中,使用不同的载体通过研磨方法制备含依托度酸的固体分散体(ETD-SD),比如羟丙甲纤维素,聚乙烯吡咯烷酮,共聚维酮,尿素,还有甘露醇.溶解度研究,溶出度试验,形态学评估,热分析,和FTIR成像用于评价SD性能。结果表明,球磨工艺可用于获得具有ETD的SD。与未加工的ETD相比,所有设计的ETD-SD的特征在于更高的水溶性和更快的溶解速率。具有无定形载流子的SDs(HPMC,PVP,和PVP/VA)提供了比具有结晶特征的分散体(尿素和甘露醇)更大的ETD溶解度。FTIR光谱证实了ETD与测试载体的相容性。
Poor water solubility of drugs is a limiting factor for their bioavailability and pharmacological activity. Many approaches are known to improve drug solubility, and among them, the physical method, solid dispersions (SDs), is applied. SDs are physical mixtures of a drug and a carrier, sometimes with the addition of a surfactant, which can be obtained by milling, cryomilling, spray-drying, or lyophilization processes. In this study, solid dispersions with etodolac (ETD-SDs) were prepared by the milling method using different carriers, such as
hypromellose, polyvinylpyrrolidone, copovidone, urea, and mannitol. Solubility studies, dissolution tests, morphological assessment, thermal analysis, and FTIR imaging were applied to evaluate the SD properties. It was shown that the ball-milling process can be applied to obtain SDs with ETD. All designed ETD-SDs were characterized by higher water solubility and a faster dissolution rate compared to unprocessed ETD. SDs with amorphous carriers (HPMC, PVP, and PVP/VA) provided greater ETD solubility than dispersions with crystalline features (urea and mannitol). FTIR spectra confirmed the compatibility of ETD with tested carriers.