酮洛芬一元与二元醇质体凝胶稳定性及体外透皮性的比较研究

Comparative study on in vitro stability and transdermal penetration of ketoprofen ethosomal gels versus binary ethosomal gels

目的比较酮洛芬(KPF)一元醇质体(KPFE)凝胶与二元醇质体(KPFBE)凝胶稳定性及体外经皮渗透行为,以期为筛选出较优的KPF外用制剂奠定基础。方法制备KPFE凝胶与KPFBE凝胶;分别对其离心稳定性及高温(60℃)、冷藏(4℃)、强光下的稳定性进行考察;以离体鼠皮为屏障,采用Franz扩散池法对KPF这两种凝胶的体外经皮渗透行为进行比较研究。结果两种凝胶在离心条件下均无分层现象,KPFE凝胶在低温及强光条件下较为稳定,但在高温条件下,含量及粒径均呈现上升的趋势,而KPFBE凝胶在实验条件下各项指标均无明显变化。两种凝胶的体外经皮渗透动力学均符合零级方程,KPFE凝胶:Q=38.04t+12.32(r=0.999 6),KPFBE凝胶:Q=54.68t-21.19(r=0.998 5),稳态透皮速率J分别为38.04μg/(cm2.h)和54.68μg/(cm2.h),体外透皮24 h后,皮肤中的蓄积量分别为18.36μg/cm2和16.79μg/cm2(P>0.05),凝胶层中的残留量为2.45 mg和1.34 mg(P<0.05)。结论与KPFE凝胶相比,KPFBE凝胶稳定性较优,能更好地促进药物的经皮吸收,值得进一步研究。

Objective To compare the in vitro stability and transdermal penetration of ketoprofen（KPF） ethosomal（KPFE） gels versus binary ethosomal（KPFBE） gels for screening the optimal external preparation for KPF. Methods KPFE gels and KPFBE gels were prepared.The stability of the two KPF gels was studied and compared after centrifugation,high temperature（60 ℃）,low temperature（4 ℃） or strong light.With skipped mouse skin as the barrier,the in vitro transdermal penetration of the two gels was studied and compared using Franz diffusion cells. Results After the centrifugation,the two gels showed no layer separation phenomenon.The stabilities of KPFE at low temperature and strong light were good,while at high temperature,the drug concentration and mean size of KPFE were increased with the testing time.Under the above experimental conditions,the stability of KPFBE was promising.Both the in vitro transdermal penetration of the two gels was fitted zero-order kinetic equation,Q=38.04t＋12.32（r=0.999 6） for KPFE gels and Q=54.68t-21.19（r=0.998 5） for KPFBE gels.The steady state penetration rate（J） was 38.04 μg/（cm2·h） for KPFE and 54.68 μg/（cm2·h） for KPFBE.After 24 h transdermal penetration,the KPF cumulative amount in skin was 18.36 μg/cm2 for KPFE gels and 16.79 μg/cm2 for KPFBE gels（P0.05）,and residual amount in the gels was 2.45 mg and 1.34 mg,respectively（P0.05）. Conclusion Compared with KPFE gels,KPFBE gels exhibit better stability and in vitro transdermal penetration in the transdermal drug delivery systems.