Purpose

The main objective of the present investigation was to develop transdermal films of ondansetron HCl (OS) with polyvinyl alcohol (PVA) using Box-Behnken design and to optimize them employing Derringer’s optimization tool.

Methods

Design-Expert software was used to investigate the effect of independent variables such as concentration (%, w/w) of glycerol and 1,8-cineole, and number of Freeze-Thaw cycle (F-T cycle) on the dependent variables viz. ultimate tensile strength (UTS) and flux. The F-T cycle followed by solvent casting method was employed to develop films. Universal tensile testing machine and Franz diffusion cell were used to measure tensile strength and flux, respectively.

Results

Quadratic model was found to be best fit model and the effect of concentration of glycerol and the number of F-T cycle significantly influences the tensile strength (p < 0.0001), whereas the concentration of 1,8-cineole significantly (p < 0.0001) influenced the flux. The optimized conditions were found to be 10% (w/w) of glycerol, 4.999 number of F-T cycle, and 7.499% (w/w) of 1,8-cineole using Derringer’s optimization tool. Under these conditions, the predicted tensile strength and flux obtained were 18.322 MPa and 30.697 μg/cm²/h, respectively, with desirability of 0.791. Skin irritation potential study on the rat showed a score of 0.44 ± 0.13 on Draize scoring system. The optimized film was found to be stable for 3 months at room temperature and accelerated conditions (40 ± 2 °C temperature and 75 ± 5% RH).

Conclusions

Above results imply that the optimized film of OS is a safe transdermal drug delivery tool which could be used as a potential alternative to oral dosage form.

中文翻译：

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基于RSM的盐酸恩丹西酮透皮膜的设计与优化

目的

本研究的主要目的是使用Box-Behnken设计开发盐酸恩丹西酮（OS）与聚乙烯醇（PVA）的透皮薄膜，并使用Derringer的优化工具对其进行优化。

方法

使用Design-Expert软件研究自变量，例如甘油和1,8-桉树脑的浓度（％，w / w），以及冻融循环数（FT循环）对因变量viz的影响。极限抗拉强度（UTS）和通量。FT循环后接着溶剂流延法用于显影膜。使用通用拉伸试验机和Franz扩散池分别测量拉伸强度和通量。

结果

发现二次模型是最佳拟合模型，甘油浓度和FT循环次数的影响显着影响抗张强度（p  <0.0001），而1,8-桉树脑的浓度显着影响（p  <0.0001）。通量。使用Derringer的优化工具，发现优化条件为甘油的10％（w / w），FT循环数4.999和1,499-桉树脑的7.499％（w / w）。在这些条件下，预计的抗张强度和通量分别为18.322 MPa和30.697μg/ cm ²/ h分别为0.791。对大鼠的皮肤刺激潜力研究显示，Draize评分系统得分为0.44±0.13。发现优化的薄膜在室温和加速条件下（40±2°C温度和75±5％RH）稳定3个月。

结论

以上结果表明，优化的OS膜是一种安全的透皮药物传递工具，可以用作口服剂型的潜在替代品。