M. M. College of Pharmacy, M. M. University, Ambala, India.
Pharm Dev Technol. 2012 Mar-Apr;17(2):158-63. doi: 10.3109/10837450.2010.522585. Epub 2010 Oct 19.
The first-line therapy for moderate to severe benign prostatic hyperplasia is the oral therapy by alfuzosin hydrochloride. Unfortunately, the oral therapy of alfuzosin is associated with several route-specific systemic side-effects. The current study was aimed to develop a prototype transdermal patch system for alfuzosin using a hydrogel polymer and optimize the drug delivery through the skin for systemic therapy. The prospective of different chemical enhancers (polyethylene glycol (PEG 400), isopropyl myristate, propylene glycol, menthol and L-methionine; 5% w/v) and iontophoresis (0.3 mA/cm(2)) in the alfuzosin delivery across the full thickness rat skin was assessed in vitro. In vivo iontophoretic studies were carried out using selected patch system (PEG 400) for a period of 6 h in Sprague-Dawley rats. Passive permeation studies indicated that the incorporation of chemical agents have moderate effect (4- to 7-fold) on the alfuzosin skin permeability and reduced the lag time. Combined approach of iontophoresis with chemical enhancers significantly augmented the drug transport ( 43- to 72-fold). In vivo pharmacokinetic parameters revealed that the iontophoresis (transdermal patch with PEG 400) significantly enhanced the C(max) (~ 3-fold) and AUC(0-α) (~ 4-fold), when compared to control. The current study concludes that the application of iontophoresis (0.3 mA/cm(2)) using the newly developed agaorse-based prototype patch with PEG 400 could be utilized for the successful delivery of alfuzosin by transdermal route.
盐酸阿夫唑嗪治疗中重度良性前列腺增生的一线药物。不幸的是，盐酸阿夫唑嗪的口服治疗与几种特定途径的全身副作用有关。本研究旨在使用水凝胶聚合物开发盐酸阿夫唑嗪的原型透皮贴剂系统，并通过皮肤优化药物输送以进行全身治疗。评估了不同化学增强剂（聚乙二醇（PEG 400）、肉豆蔻酸异丙酯、丙二醇、薄荷醇和 L-甲硫氨酸；5%w/v）和离子电渗（0.3 mA/cm(2)）对盐酸阿夫唑嗪在全厚大鼠皮肤中的传递的前景。在体外，使用选定的贴剂系统（PEG 400）进行了 6 h 的体内离子电渗研究。被动渗透研究表明，化学试剂的加入对盐酸阿夫唑嗪的皮肤渗透性有适度的影响（4-7 倍），并减少了滞后时间。离子电渗与化学增强剂的联合作用显著增加了药物输送（43-72 倍）。体内药代动力学参数表明，与对照组相比，离子电渗（含有 PEG 400 的透皮贴剂）显著提高了 C(max)（3 倍）和 AUC(0-α)（4 倍）。本研究得出结论，使用新开发的基于琼脂糖的原型贴剂和 PEG 400 施加 0.3 mA/cm(2)的离子电渗，可以通过透皮途径成功输送盐酸阿夫唑嗪。
