Study On Chlorphenesin Carbamate Cream

Objective:Chlorphenesin Carbamate is a central muscle relaxant, which was recorded in JP12,13,14,15. The aim of the present study was to prepare Chlorphenesin Carbamate cream and investigate its quality and stability.Method:At first orthogonal design L9(43) was carried out in order to choose the proportion of glyceryl monostearate, octadecanol, stearic acid and liquid paraffin in oil phase. The response of the experiment include:emulsification condition, applyment, glossiness, whiteness and consistence. On this basis, penetration enhancers were added. The enhancing effects of all these creams were inspected and the best combination was chosen by means of homogeneous design. Single factor experiments were used to select the best HLB value and usage amount of emulsifier. The temperature when emulsifying was optimized. Different preparative methods were compared to choose a way that can ensure CPC, menthol crystal and ethylparaben were dissolved in cream. CPC cream was produced according to the optimized formulation.Quality evaluation of this cream had been finished, including emulsification condition, applyment, glossiness, whiteness, consistence, skin permeation rate, content and related substance.Stress testing, destructive test, accelerated testing and long-term testing were carried out according to guidance for stability testing of new drug substance and products.Results:According to orthogonal design experiments, the prescription was determined that there should be glyceryl monostearate1.5g, octadecanol1g, stearic acid0.3g and liquid paraffin5g in50g cream. In vitro skin permeation study was taken on skin from mouse that weight25±2g, and30%alcohol-normal saline solution was used as receiving mediator. The amount that CPC permeated was measured by UV. Permeation enhancer was determined to be2.5%menthol crystal and0.01%capsicine. The HLB of emulsifier was12.4. The best usage amount of emolsifier was0.05g in50g cream. The cream was prepared by means of encapsulate CPC into micellar and then melt it into water. The content and related substance of CPC was measured by HPLC method on silica gel column with a mixture of n-hexane:isopropanol:glacial acetic acid (800:200:1) as mobile phase at a flow rate of0.8ml·min-1under the wavelength of281nm. The content of CPC in cream was95.86%, and the related substance was1.15%. The skin permeation was repeated, which could be detected by HPLC method on C18column with a mixture of triethylamine solution (triethylamine10ml in500ml, add phosphoric acid until pH gets3.0):methanol(50:50) as mobile phase at a flow rate of0.7ml·min-1under the wavelength of280nm. The process that CPC permeated was analyzed by means of permeation curves with a average slope at0.1435.The results of stress testing showed that cream was stable to high temperature at30℃and highlight at4500±500lx. Result of accelerated testing and long-term testing showed that cream were stable during disposition.Conclusion:The prepared cream had pleasant stability. The method was convenient, stable and reliable for the quality control in CPC cream. It was suggested that this cream prepared should be stored at a temperature below30℃.