丁香酚微乳凝胶的制备及其体外释放特性研究

目的制备高载药量、高黏附性的丁香酚微乳凝胶,以提高丁香酚的透皮渗透性和相对生物利用度。方法通过表观溶解度评价丁香酚在油、表面活性剂和助表面活性剂中的溶解度,以筛选微乳的处方组成。以油酸乙酯为油相,Solutol HS15为表面活性剂和PEG 400为助表面活性剂,纯化水为水相构建伪三元图。评价微乳的pH值、电导率、黏度、粒径和药物浓度。通过甘油润湿的卡波姆940配制成微乳凝胶,并评价微乳凝胶的pH值、粒径、黏度和药物浓度。采用改良Franz扩散池法对丁香酚微乳凝胶的体外释放性能进行考察。结果表面活性剂和助表面活性剂之比为1∶1时,形成的微乳区域最大;微乳(F3)的球体尺寸为83.27 nm,含量稳定。加入0.5%卡波姆940和6%甘油制得外观均匀、透明的微乳凝胶,微乳(F3)黏度为106.8 mPa·s,微乳凝胶(FG3)黏度增加到15.7 Pa·s。体外经皮渗透试验表明丁香酚对照品溶液、微乳和微乳凝胶的经皮累积渗透率依次增大,微乳凝胶(FG3)渗透12h后丁香酚经皮累积渗透量为55.08%。家兔刺激试验结果表明其在家兔皮肤上没有刺激或诱导炎症。结论丁香酚微乳凝胶比丁香酚对照品溶液、丁香酚微乳具有更好的应用性和稳定性,有望成为丁香酚的新型给药制剂。

Preparation of Eugenol Microemulsion Gel and Study on Its in Vitro Release Characteristics

ABSTRACT: OBJECTIVE We aimed to prepare a eugenol microemulsion gel with high drug content and adhesiveness to improve transdermal penetration and relative bioavailability of eugenol. METHODS The solubilities of eugenol in oils, surfactants and cosurfactants were evaluated to screen the components of microemulsion. Pseudo-ternary phase diagrams were constructed by using ethyl oleate, Solutol HS15 and PEG 400, purified water as the oil phase, surfactant and cosurfactant, respectively. The pH, conductance, viscosity, particle size and drug content of this microemulsion were measured. The optimized system was formulated into a gel form by using Carbopol 940 and glycerin, and its viscosity, drug content, stability, in vitro diffusion and skin irritability were evaluated. RESULTS When the surfactant/cosurfactant ratio was 1:1, the largest microemulsion region formed. The particle size of microemulsion F3 was 88.75 nm, with a stable content. A homogeneous and transparent microemulsion gel was obtained by adding 0.5% Carbopol 940 and 6% glycerin. The viscosities of microemulsion F3 and microemulsion gel FG3 were 106.8 mPa·s and 15.7 Pa·s respectively. In vitro diffusion study showed that the cumulative infiltration amounts of eugenol standard solution, microemulsion and microemulsion gel followed an ascending order. The 12 h cumulative infiltration amount of microemulsion gel FG3 reached 57.15%. Rabbit irritation study exhibited that the skin was not irritated or inflamed. CONCLUSION Eugenol microemulsion gel had higher applicability and stability than those of eugenol solutionand eugenol microemulsion, as a promising a new drug delivery formulation.