Mottola Stefania, De Marco Iolanda
Department of Industrial Engineering, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy.
Research Centre for Biomaterials BIONAM, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy.
Polymers (Basel). 2023 Dec 20;16(1):29. doi: 10.3390/polym16010029.
In this study, corticosteroid-β-cyclodextrin (β-CD) inclusion complexes were prepared by using supercritical antisolvent (SAS) precipitation to enhance the dissolution rate of dexamethasone (DEX) and prednisolone (PRED), which are poorly water soluble drugs. The processing of the active principles in the absence of a carrier led to their almost complete extraction (the small amount of obtained material precipitates in the form of crystals). The coprecipitation of the ingredients in the presence of β-CD was investigated at different concentrations, pressures, and molar ratios. For both the corticosteroids, the optimized operating conditions were 40 °C, 120 bar, an equimolar ratio, and a concentration in DMSO of 20 mg/mL; these conditions led to the attainment of microparticles with mean diameters equal to 0.197 ± 0.180 μm and 0.131 ± 0.070 μm in the case of DEX and PRED, respectively. Job's method confirmed the formation of inclusion complexes with a 1/1 mol/mol ratio. Compared to the pure ingredients, the obtained powders have an improved release rate, which is about three times faster in both cases. The release curves obtained under the best operating conditions were fitted using different models. The best fitting was obtained using the Weibull model, whose parameters are compatible with a combined release mechanism involving Fickian diffusion and controlled release.
在本研究中,通过超临界抗溶剂(SAS)沉淀法制备了皮质类固醇-β-环糊精(β-CD)包合物,以提高地塞米松(DEX)和泼尼松龙(PRED)这两种水溶性差的药物的溶解速率。在没有载体的情况下对活性成分进行处理,导致它们几乎被完全萃取(少量获得的物质以晶体形式沉淀)。研究了在不同浓度、压力和摩尔比下,β-CD存在时各成分的共沉淀情况。对于这两种皮质类固醇,优化的操作条件为40℃、120巴、等摩尔比以及在二甲基亚砜中的浓度为20mg/mL;在这些条件下,分别得到了平均直径等于0.197±0.180μm和0.131±0.070μm的微粒,分别对应DEX和PRED。乔布法证实形成了摩尔比为1/1的包合物。与纯成分相比,所得粉末具有更高的释放速率,在两种情况下都快约三倍。使用不同模型对在最佳操作条件下获得的释放曲线进行拟合。使用威布尔模型获得了最佳拟合,其参数与涉及菲克扩散和控释的联合释放机制相符。