Department of Pharmaceutics, The University of Mississippi, University, MS 38677, USA.
J Control Release. 2010 Mar 19;142(3):361-7. doi: 10.1016/j.jconrel.2009.10.036. Epub 2009 Nov 14.
The electroporation mediated transdermal delivery (Protocol - 120 V, 10 ms, 30 pulses at 1 Hz with post pulse waiting period of 20 min) of doxepin using pure drug solution (PDS) and doxepin-hydroxypropyl-beta-cyclodextrin (HPCD) complex solution (CDS) was studied using porcine epidermis model. The stoichiometry of drug-HPCD inclusion complex was determined by differential scanning calorimetry (DSC). The amount of doxepin retained in the epidermis following electroporation did not differ significantly between PDS and CDS. When the drug loaded epidermis was subjected to "Release studies", doxepin release attained a plateau within approximately 2.5 days in case of PDS, whereas in case of CDS, doxepin release was prolonged up to 5 days. Mechanistic studies across the nonbiological barriers demonstrated that the slow dissociation of complex was responsible for sustained release of drug from the epidermis. Pharmacodynamic studies were carried out by electroporation mediated delivery of CDS and PDS in hairless rats. The analgesic effect of doxepin was prolonged in case of CDS as compared to PDS.
采用电穿孔介导透皮给药（方案-120V、10ms、1Hz 时 30 个脉冲，脉冲后等待期 20min），分别用单纯药物溶液（PDS）和盐酸多塞平-羟丙基-β-环糊精（HPCD）包合物溶液（CDS）研究盐酸多塞平经皮给药。采用差示扫描量热法（DSC）测定药物-HPCD 包合物的化学计量比。电穿孔后，表皮中保留的盐酸多塞平的量在 PDS 和 CDS 之间无显著差异。当负载药物的表皮进行“释放研究”时，PDS 中盐酸多塞平的释放在大约 2.5 天内达到平台期，而在 CDS 中，盐酸多塞平的释放延长至 5 天。跨非生物屏障的机制研究表明，复合物的缓慢解离是药物从表皮持续释放的原因。通过无毛大鼠的电穿孔介导递送 CDS 和 PDS 进行药效学研究。与 PDS 相比，CDS 中的盐酸多塞平的镇痛作用延长。
