Development and evaluation of wafer loaded with sertaconazole solid dispersion for the treatment of oral candidiasis

Abstract Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.

摘要 念珠菌病是人类最常见的口腔真菌感染性疾病之一，可引发显著口腔不适、疼痛及食欲减退。为开发更高效的口腔念珠菌病治疗用抗真菌给药系统，本研究制备了含舍他康唑固体分散体（sertaconazole solid dispersion，STZ-SD）的口腔黏膜黏附片。以Soluplus®作为增溶辅料，在不同STZ与Soluplus®质量配比条件下，采用熔融法、溶剂蒸发法与冷冻干燥法制备STZ-SD。随后将优化得到的STZ-SD分别掺入羧甲基纤维素钠（sodium carboxymethyl cellulose，SCMC）凝胶、黄原胶凝胶或二者的混合凝胶中，制备冻干口腔黏膜黏附片。对所得冻干片的溶胀能力、孔隙率、力学性能、释放特性、黏膜黏附性能及抗真菌活性进行了评价。结果显示，质量配比为8:1的熔融法制备样品在饱和溶解度与溶出速率方面表现最优。相较于单一SCMC聚合物制备的贴片，STZ-SD复合贴片具备更高的硬度与更优异的黏膜黏附性能。同时，STZ-SD贴片的抗真菌效果亦优于单纯舍他康唑贴片。综上，本研究证实STZ-SD贴片可作为一种新型高效的口腔念珠菌病治疗给药系统。