吴茱萸次碱透皮贴剂的处方优化

Formulation Optimization of Rutaecarpine Transdermal Patch

目的筛选吴茱萸次碱(Rut)透皮贴剂的压敏胶和促渗剂。方法用溶剂挥发法制备贴剂,以黏附力(初黏力、持黏力及剥离强度)为指标,采用Box-Behnken设计筛选压敏胶(Eudragit E100)、交联剂(丁二酸)和增塑剂(癸二酸二丁酯)的配比;以黏附力和经皮渗透性为指标,以离体小鼠皮肤为屏障,采用改良Franz扩散池进行透皮吸收试验,采用定制设计筛选压敏胶基质、促渗剂(氮酮、油酸)的配比。结果 Rut透皮贴剂的处方最佳配比:压敏胶基质83%(Eudragit E100 63.5%、丁二酸5.5%、癸二酸二丁脂14%)、氮酮10%、油酸6.4%,Rut 0.6%。初黏力、持黏力和剥离强度分别为15号球,(10.97±0.32)h和(0.16±0.02)kN·M^(-1),Q_(24)和J_s分别为(29.71±1.19)μg·cm^(-2)、(1.36±0.10)μg·cm^(-2)·h^(-1)。结论优化的Rut透皮贴剂具有良好的黏附性和经皮渗透性,为后续研究提供了实验依据。

OBJECTIVE To screen pressure sensitive adhesive system and penetration enhancer of rutaecarpine transdermal patch. METHODS The patch was prepared by solvent evaporation method. The ratio between pressure sensitive adhesive （Eudragit El00 ）, crosslinking agent （succinic acid） and plasticizer （dibutyl sebacate） of the rutaecarpine patch were screened through Box-Be- hnken design by using adhesion （stick power, shear strength, peel force） as the index. The ratio between pressure sensitive adhesives and chemical enhancers （azone and oleic acid） were screened by adhesion and permeation experiments in vitro using custom design, which were carried out by using improved Franz diffusion ceils through excised mice skin. RESULTS The optimized formulation of rutaecarpine transdermal patch consisted of 83% pressure sensitive adhesives （63.5% Eudragit El00, 5.5% succinic acid, 14% dib- utyl sebacate） , 10% azone, 6.4% oleic acid and 0. 6% rutaecarpine. The stick power, shear strength, and peel force of the patch were 15 steel bails, （10. 97 ±0. 32） h and （0. 16 ±0. 02） kN · M-l, respectively. The cumulative permeation amount and perme- ation rate of the patch were （29. 71 ± 1.19） μg · cm-2 and （ 1.36 ± 0. 10）μg · cm-2 . h-1, respectively. CONCLUSION The optimized rutaecarpine patch show increased permeation and appropriate adhesion. This study provides the basis for future research.