萜类促渗剂对盐酸普萘洛尔凝胶体外经皮渗透的影响

黎绫,何世英,张海龙,叶崎,丁劲松*

中国药学杂志 ›› 2015, Vol. 50 ›› Issue (1) : 63-67.

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中国药学杂志 ›› 2015, Vol. 50 ›› Issue (1) : 63-67. DOI: 10.11669/cpj.2015.01.016
论著

萜类促渗剂对盐酸普萘洛尔凝胶体外经皮渗透的影响

  • 黎绫,何世英,张海龙,叶崎,丁劲松*
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Effect of Novel Terpenes Penetration Enhancer on in-vitro Percutaneous Penetration of Propranolol Hydrochloride Hydrogel

  • LI Ling, HE Shi-ying, ZHANG Hai-long ,YE Qi, DING Jin-song*
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文章历史 +

摘要

目的 考察萜类促渗剂的种类、浓度及联用对盐酸普萘洛尔(PPL·HCl)经皮渗透的影响,为盐酸普萘洛尔经皮递药系统的处方筛选提供依据。方法 采用改良Franz直立式扩散池,离体乳猪皮肤为渗透屏障,以体外经皮累积渗透量(Q)和促渗倍数(ER)为指标,比较萜类促渗剂对盐酸普萘洛尔经皮渗透的影响。结果 10种萜类促渗剂对凝胶中盐酸普萘洛尔体外经皮渗透促进作用顺序为:法尼醇>L-薄荷脑>橙花叔醇>四氢香叶醇>1,4-桉叶素≈香叶醇>柠檬烯>茴香脑>冰片>甘草酸二钾,均符合零级渗透规律,其中法尼醇、L-薄荷脑、橙花叔醇浓度为3%时具有最高的Q,最大的ER;浓度增至5%,其促渗作用反而降低;与单用3%促渗剂相比,与异丙醇联用具有协同促渗作用(P<0.05),而与丙二醇联用则显示拮抗作用(P<0.05)。结论 新型萜类促渗剂(除甘草酸二钾)均能不同程度促进盐酸普萘洛尔经皮渗透,促渗剂为3%法尼醇+10%异丙醇时,盐酸普萘洛尔体外透皮可达最大吸收,该结果为盐酸普萘洛尔经皮给药研究提供了基础。

Abstract

OBJECTIVE To investigate the effects of different novel terpenes penetration enhancers and their combinations on percutaneous absorption of propranolol hydrochloride hydrogel and screen the best penetration enhancers so as to increase the cumulative permeation quantity in the target site. METHODS The percutaneous permeation experiment was carried out with modified Franz-type diffusion cell with isolated piglet skin as the barrier. The effects of the types, concentrations, and combinations of penetration enhancers on the transdermal penetration of propranolol hydrochloride hydrogel were compared using cumulative permeation quantity (Q) and enhancing rate (ER) as indexes. RESULTS The effectiveness of terpenes was found to be the optimal at concentration of 3% in the following order: farnesol>L-menthol>nerolidol>tetrahydrogeraniol>1,4-cineole≈geraniol>limonene>anethole>borneol>negative control>dipotassium glycyrrhizic acid. The release profiles from the hydrogel formulations obeyed zero-order kinetics. Farnesol, L-menthol, and nerolidol effectively promoted the percutaneous penetration of propranolol hydrochloride over the concentration range of 1%-5%. The enhancement ratio was the highest at 3% and decreased if the concentration increased to 5%. Significant synergism was observed when the enhancers were used in combination(P<0.05), while there was an antagonistic effect when 3% farnesol or 3% L-menthol was combined with propylene glycol(P<0.05). CONCLUSION The percutaneous absorption of propranolol hydrochloride is increased by the terpenes enhancers and reached the peak value with 3% farnesol plus 10% isopropanol. These findings provide a basis for the further transdermal delivery studies of propranolol hydrochloride.

关键词

盐酸普萘洛尔 / 水凝胶 / 萜类促渗剂 / 经皮渗透 / 血管瘤

Key words

propranolol hydrochloride / hydrogel / terpenes penetration enhancer / percutaneous penetration / hemangioma

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导出引用
黎绫,何世英,张海龙,叶崎,丁劲松*. 萜类促渗剂对盐酸普萘洛尔凝胶体外经皮渗透的影响[J]. 中国药学杂志, 2015, 50(1): 63-67 https://doi.org/10.11669/cpj.2015.01.016
LI Ling, HE Shi-ying, ZHANG Hai-long ,YE Qi, DING Jin-song*. Effect of Novel Terpenes Penetration Enhancer on in-vitro Percutaneous Penetration of Propranolol Hydrochloride Hydrogel[J]. Chinese Pharmaceutical Journal, 2015, 50(1): 63-67 https://doi.org/10.11669/cpj.2015.01.016
中图分类号: R944   

参考文献

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