使用棕榈油基质的新型睾酮透皮给药系统（TTDS）的体外和体内评价

In vitro and in vivo evaluation of a novel testosterone transdermal delivery system (TTDS) using palm oil base.

作者信息

Haron Didi Erwandi Mohamad, Chik Zamri, Noordin Mohamed Ibrahm, Mohamed Zahurin

机构信息

Shimadzu-UMMC Center for Xenobiotics Studies (SUCXeS), University of Malaya, 50603 Kuala Lumpur, Malaysia.

Shimadzu-UMMC Center for Xenobiotics Studies (SUCXeS), University of Malaya, 50603 Kuala Lumpur, Malaysia; University of Malaya Bioequivalence and Testing Center (UBAT), Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

出版信息

Iran J Basic Med Sci. 2015 Dec;18(12):1167-75.

PMID:26877845

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4744355/

Abstract

OBJECTIVE S

Transdermal preparations for testosterone are becoming popular because of their unique advantages such as avoidance of first-pass effect, convenience, improved bioavailability, and reduction of systemic side effects. A novel testosterone transdermal delivery system (TDDS) was developed using a palm oil base called HAMIN™ (a commercial product) and tested using in vitro and in vivo skin permeability test methods.

MATERIALS AND METHODS

The physical characteristics of the formulation such as particle size and viscosity were determined by using Franz diffusion cell and Brookfield viscometer, respectively. In vivo skin permeability test was performed on healthy rabbits through the skin. Testosterone in serum was analyzed using the validated Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) technique.

RESULTS

In vitro study showed that the cumulative amount of testosterone diffused was between 40 to 1400 ngcm(-)² over a period of five hr after application of TDDS through the artificial Strat-M™ membrane. In the in vivo rabbit skin permeability test, the results indicated that testosterone was well absorbed with a mean Cmax and Tmax of 60.94 ngml(-1) and 2.29 hr after application of TDDS while no increase was observed in placebo treatment. Particle size analysis ranged from 79.4 nm to 630.0 nm for placebo and 97 to 774.0 nm for TDDS.

CONCLUSION

The formulation was successfully prepared using HAMIN™, which has demonstrated great potential for topical delivery of testosterone.

摘要

目的

由于透皮睾酮制剂具有避免首过效应、使用方便、生物利用度提高以及全身副作用减少等独特优势，其正变得越来越受欢迎。一种新型的睾酮透皮给药系统（TDDS）采用名为HAMIN™（一种商业产品）的棕榈油基质开发，并通过体外和体内皮肤渗透性测试方法进行了测试。

材料与方法

分别使用Franz扩散池和Brookfield粘度计测定制剂的粒径和粘度等物理特性。对健康兔子进行了体内皮肤渗透性测试。采用经过验证的液相色谱 - 串联质谱（LC - MS/MS）技术分析血清中的睾酮。

结果

体外研究表明，通过人工Strat - M™膜应用TDDS后，在5小时内睾酮的累积扩散量在40至1400 ngcm(-)²之间。在体内兔子皮肤渗透性测试中，结果表明应用TDDS后睾酮吸收良好，平均Cmax和Tmax分别为60.94 ngml(-1)和2.29小时，而安慰剂处理未观察到增加。安慰剂的粒径分析范围为79.4 nm至630.0 nm，TDDS为97至774.0 nm。