Compatibility of raw material and excipients in dexmetomidine hydrochloride gel / 国际药学研究杂志

ABSTRACT

Objective: To establish a method for the determination of related substances in dexmetomidine hy- drochloride gels,and investigate the compatibility of dexmedetomidine hydrochloride and excipients in the dexmetomi- dine hydrochloride gels. Methods: HPLC was performed on an octadecylsilane bonded silica gel column by a gradient elution with acetonitrile/0.008 mol/L NaH2PO4 solution as mobile phase. Flow rate was 1.0 ml/min. Column temperature was 30℃. Injection volume was 50 μl. Detection wavelength was 210 nm. According to the Basic Technical Guidelines for the Research of Chemical Drug Preparations,dexmetomidine hydrochloride was mixed with excipients in a certain propor- tion,and the mixtures were treated as test sample at the conditions of high temperature(60℃)and strong light(4500± 500)Lx irradiation. Sampling was performed on the 0,10th and 30th day of treatment,respectively. The appearance of the test samples was examined,and related substances in the samples were determined by the established HPLC method. Results: The established HPLC method showed a good specificity and durability,which could be used to accurately and effectively determine the changes of related substances. The appearance of the test samples the mixtures of dexmetomi- dine hydrochloride and excipients showed no changes in the full course of treatment at the tested conditions,and the re- lated substances were also not increased under the same conditions. Conclusion: The selected excipients(HPMC,pro- pylene glycol,methylparaben,sodium benzoate,and benzyl alcohol)all showed a good compatibility with dexmetomi- dine hydrochloride,and the tested mixture samples with the excipients and dexmetomidine hydrochloride were stable un- der the conditions of high temperature and strong light irradiation. These excipients could be used for the formulation screening for the dexmedetomidine hydrochloride gel development.