塞来昔布醇质体凝胶的制备及其透皮吸收研究

Preparation and Transdermal Penetration of the Gel Based on Celecoxib Ethosomes

采用乙醇注入法制备塞来昔布醇质体,以超速离心法测定包封率,用其为评价指标,通过正交设计优化处方。所得优化处方在透射电镜下呈球形,包封率为(72.56±0.29)%,动态光散射法测得其粒径(189.4±0.8)nm,多分散系数为0.322±0.012,ζ电位为(-21.58±0.26)m V。以卡波姆934为凝胶基质,分别制备了基于塞来昔布醇质体的凝胶和普通凝胶。以小鼠为模型的离体透皮试验结果表明,塞来昔布醇质体凝胶与普通凝胶的稳态渗透速率为(17.89±0.18)和(7.62±0.12)μg·cm^(-2)·h^(-1),12 h时皮肤滞留量为(13.62±0.17)和(5.69±0.25)μg/cm^2。可见,塞来昔布醇质体凝胶能显著增加药物的渗透速率与皮肤滞留量,是一种较有前景的经皮给药系统。

The celecoxib ethosomes were prepared by ethanol injection method and the entrapment efficiency was detemined by ultracentrifugation. The formulation of the ethosomes was optimized by orthogonal design with entrapment efficiency as the index. The morphology of the optimal ethosomes was observed by transmission electron microscopy （TEM）, and the partical size and ζ potential were conducted with the help of dynamic light scattering. The results showed that the optimal product had a spherical shape with the mean entrapment efficiency of （72.56±0.29）%.The average partical size, polydispersity index and ζ potential were （189.4±0.8）nm, 0.322±0.012 and （-21.58±0.26）mV,respectively. Then, the gels based on the optimal ethosomes and the bulk drug were prepared with Carbopor 934 as a gel matrix. The in vitro transdermal test were carried out with excised mouse skin as the barriers to compare the permeation amount and skin retention of the above two gels. The results showed that the steady penetration rates of celecoxib ethosomal gel and celecoxib gel were （17.89±0.18） and （7.62±0.12）μg·cm-2·h-1, while the retention amounts at 12 h were （13.62±0.17） and （5.69±0.25）μg/cm2. It indicated that the celecoxib ethosomal gel might to be a promising carrier of transdermal delivery for celecoxib because of the significant increasing in both the permeation rate and skin retention.