Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Colloids Surf B Biointerfaces. 2013 Jan 1;101:143-51. doi: 10.1016/j.colsurfb.2012.06.015. Epub 2012 Jun 26.
The main objective of this study was to develop a microemulsion (ME) formulation for transdermal delivery of ondansetron for chemotherapy induced nausea and vomiting (CINV). For the formulation development oil was selected on the basis of drug solubility in it while the surfactants and co-surfactants (S(mix)) were screened on the basis of their capacity to solubilize the oil as well as their efficiency to provide the microemulsion area. The microemulsion existence ranges were defined through the construction of the pseudo-ternary phase diagram and various formulations were developed. Effect of surfactant and cosurfactant mass ratio (S(mix)) on the microemulsion formation and its permeation through excised rat skin was studied. A significant increase in permeability parameters such as steady-state flux (J(ss)), permeability coefficient (K(p)), and enhancement ratio (ER) was observed in ME. Formulation B4 which consisted of 0.5% (w/w) of ondansetron, 5% (w/w) of oleic acid, 30% (w/w) S(mix) (2:1, Tween 20 and PEG 400) and 64.5% (w/w) of distilled water showed the best permeability profile. The formulation B4 was subjected to various in vitro attributes and converted to microemulsion gel (OMG). In order to predict the efficacy, pharmacokinetic studies were performed and pharmacokinetic profile was compared with ondansetron conventional gel (OCG) and oral marketed syrup (ONDANZ). The absorption of ondansetron from OMG resulted in 6.03 fold increase in bioavailability as compared to oral conventional syrup and 9.66 times with reference to the OCG gel. The future perspective includes preclinical, toxicological and clinical studies for developing clinically viable formulation.
本研究的主要目的是开发一种用于经皮递送昂丹司琼治疗化疗引起的恶心和呕吐（CINV）的微乳配方。在进行配方开发时，根据药物在其中的溶解度选择油相，而表面活性剂和助表面活性剂（S(mix)）则根据其溶解油相的能力以及提供微乳区域的效率进行筛选。通过构建伪三元相图来定义微乳存在范围，并开发了各种配方。研究了表面活性剂和助表面活性剂质量比（S(mix)）对微乳形成及其通过离体大鼠皮肤渗透的影响。在微乳中观察到渗透参数如稳态通量（J(ss)）、渗透系数（K(p)）和增强比（ER）显著增加。由 0.5%（w/w）昂丹司琼、5%（w/w）油酸、30%（w/w）S(mix)（2:1，吐温 20 和聚乙二醇 400）和 64.5%（w/w）蒸馏水组成的配方 B4 显示出最佳的渗透特性。该配方 B4 经过各种体外特性测试后转化为微乳凝胶（OMG）。为了预测疗效，进行了药代动力学研究，并将药代动力学特征与昂丹司琼常规凝胶（OCG）和口服市售糖浆（ONDANZ）进行了比较。OMG 中昂丹司琼的吸收使生物利用度增加了 6.03 倍，与口服常规糖浆相比增加了 9.66 倍，与 OCG 凝胶相比增加了 9.66 倍。未来的研究方向包括开发临床可行制剂的临床前、毒理学和临床研究。
