非水溶媒水合氯醛灌肠剂的制备及体外释放研究

Preparation and in vitro release of non-aqueous solvents chloral hydrate enema

目的采用非水溶媒制备一种高稳定性的水合氯醛灌肠剂,以解决水合氯醛在水溶液中不稳定的问题。方法以日本市售水合氯醛灌肠剂为参比制剂,考察以非水溶媒甘油和PEG 400作为辅料制备的水合氯醛灌肠剂在不同pH调节剂中的稳定性,筛选出适宜的pH调节剂;同时考察制剂在不同pH中的稳定性以确定制剂的pH,得到最佳处方,并与水合氯醛水溶液的稳定性进行比较;采用透析袋进行体外释放研究评估其释放能力,并拟合释放模型。结果最优处方为使用盐酸调节水合氯醛灌肠剂的pH为2.5。采用非水溶媒制备的水合氯醛灌肠剂与水合氯醛水溶液相比稳定性更好。自研制剂与日本市售水合氯醛灌肠剂体外释放相似,药物释放均服从Ritger peppas方程。结论本研究制备的非水溶媒水合氯醛灌肠剂工艺简单可靠,处方重现性好,稳定性佳,具有良好的应用前景。

Objective To prepare a highly stable chloral hydrate enema with non-aqueous solvents to solve the problem of chloral hydrate enema being unstable in water.Methods Commercially available chloral hydrate enema from Japan was used as a reference formulation.The stability of chloral hydrate enema prepared with non-aqueous solvents glycerol and PEG 400 as excipients was determined in different pH adjusters.Suitable pH adjusters were screened;the stability of the formulation in different pH values was also investigated to determine the pH of the formulation and to obtain the optimal prescription.The stability of the formulation was compared with that of aqueous solution;in vitro release studies were conducted with dialysis bags to assess the release capacity and a release model was fitted.Results The optimal prescription included the chloral hydrate enema was set at pH 2.5(adjusted with hydrochloric acid).The chloral hydrate enema prepared with a non-aqueous solvent was more stable than that of aqueous chloral hydrate solution.The in vitro release of the self-developed agent was similar to that of the commercially available chloral hydrate enema in Japan,with drug release obeying the Ritger peppas equation.Conclusion The non-aqueous solvents chloral hydrate enema prepared in this study is simple,reliable,reproducible,and stable,and has good application prospects.