盐酸米诺环素软膏含量及释放度测定方法研究

Study on Content and Release Determination of Minocycline Hydrochloride Ointment

目的:测定盐酸米诺环素软膏的含量及体外释放度,探讨其释药机制。方法:采用高效液相色谱法。色谱柱为InertsilC8-3,流动相为0.2mol/L醋酸铵-N,N二甲基甲酰胺-四氢呋喃(600:398:2,内含0.01mol/L乙二胺四乙酸二钠),流速为1ml/min,柱温为室温,检测波长为274nm。采用自制药盒进行体外释放度研究,方法为桨法,释放介质为水500ml,转速为100r/min,温度为(37.0±0.5)℃,释放时间为1、4、8、12、24h;对释药数据采用不同的模型进行拟合。结果:盐酸米诺环素检测质量浓度线性范围为0.05～1.90mg/m(lr=0.9997,n=5),平均回收率为100.1%,RSD=0.61%(n=9)。制剂在1、4、8、12、24h的体外释放度分别为11.03%、25.01%、36.14%、51.06%、64.62%,各拟合方程相关系数均相似且接近1,其中以按一级方程拟合的相关系数最大(r=0.9990)。结论:建立的含量和体外释放度测定方法操作简便、快速、准确度好,能有效控制盐酸米诺环素软膏的质量;该制剂具有复合释药机制,但以一级释放机制更明显。

OBJECTIVE ： To determine the content and release rate in vitro of Minocycline hydrochloride ointment, and to dis- cuss the mechanism of drug release. METHODS： HPLC method was adopted. The Inertsil C8-3 column was adopted with mobile phase consisted of 0：2 mol/L ammonium acetate-DMF-THF （600：398：2, including 0.01 mol/L EDTA-2Na） at the flow rate of 1 ml/ min. The detection wavelength was set at 274 nm under room temperature. Self-made kit was used to determine release rate in vitro. Paddle method was adopted using 500 ml distilled water as medium at rotational speed of 100 r/min and the temperature of （37.0 ± 0.5） ℃. Release time of them were 1, 4, 8, 12 and 24 h, and the data of drug release was fitted with different models. RE- SULTS： The linear range of minocycline hydrochloride was 0.05-1.90 mg/ml （r=0.999 7, n=5）, with an average recovery Of 100.1% （RSD=0.61%, n=9）. The release rate in vitro of the preparation at 1, 4, 8, 12, 24 h was 11.03%, 25.01%, 36.14%, 51.06% and 64.62% , respectively, which showed that the related coefficient fitted by equations were similar and close to 1, among which that fitted by first-order equation was the greatest （r=0.999 0）. CONCLUSIONS： Established method is simple, rap- id and accurate, and it is suitable for the quality control of minocycline hydrochloride and ointment. The ointment displays the ex- tended-release function, and first-order release is more obvious.