新型疏水化羟丙甲基纤维素硬脂氧醚乳剂型凝胶的处方设计与优化

Formulation and optimization of emulgel based on hydroxypropylmethylcellulose stearoxy ether

目的研究利用新型疏水化纤维素醚-羟丙甲基纤维素硬脂氧醚(hydroxypropylmethylcellulose stearoxy ether,Sangelose,SGL)制备乳剂型凝胶的处方及优化。方法以Sangelose 90 L、Span60、十八醇、液体石蜡用量作为影响因素,以乳剂型凝胶的手感、粒度大小、离心分层比作为响应指标,采用正交设计法进行处方优化;并以难溶性药物醋酸曲安奈德(triamcinolone acetonide acetate,TAA)及水溶性药物盐酸利多卡因(lidocaine hydrochloride,LH)作为模型药,采用改良的Franz扩散池进行体外释放试验,考察此乳剂型凝胶的释药特征,并通过模型拟合阐明其释药机制。结果优选处方为(w):0.6%Sangelose 90 L、0.5%Span 60、0.5%十八醇和8%液体石蜡。优选处方中TAA与LH在24 h的累积释放量分别为25.1%、71.8%。模型拟合结果显示,TAA的释放模型符合一级动力学,释药机制以骨架溶蚀为主;LH释放符合Higuchi方程,释药机制为药物扩散和骨架溶蚀协同作用。结论在Sangelose乳剂型凝胶中难溶性药物释放机制以骨架溶蚀作用为主,水溶性药物释放机制为扩散和骨架溶蚀的协同作用。

Objective To study the formulation and preparation of emulgel using hydroxypropylmethylcellu- lose stearoxy ether （ Sangelose ） as gelling agent. Methods Orthogonal design was employed with the amounts of Sangelose 90L, Span 60, stearyl alcohol and liquid paraffin as the investigation objects. The evaluation indexes were hand feel, mean diameter and centrifugal separation ratio. Triamcinolone acetonide acetate （TAA, water-insoluble）and lidocaine hydrochloride（ LH, water-soluble）as model drugs were loaded in this Sangelose emulgel. In vitro release test was carried out by using an improved Franz diffusion cell and the drug release mechanism was elucidated by fitting to different mathematical models. Results The optimized formulation was 0. 6% Sangelose,0. 5% Span 60,0. 5% stearyl alcohol and 8% liquid paraffin. The accu- mulated release rates （ % ） of TAA and LH from optimized formulation in 24 hours were found to be 25.1% and 71.8% respectively. The release data of TAA and LH were fitted best to first order（TAA） and Higuchi square root kinetic models （LH）. Conclusions The release mechanism of water-insoluble drug from the Sangelose emulgel was erosion depended, however, water-soluble drug was synergistic effect of diffusion and erosion depended.