Instantly dissolving buccal films have gained attention owing to their easy administration and capability to surmount the hepatic first pass effect of drugs. Dapoxetine hydrochloride (DPX) has a low oral bioavailability due to significant hepatic first pass metabolism. In addition, DPX is a weakly basic drug with a pH dependent solubility that could limit its dissolution in the body neutral fluids. In order to surpass these challenges, this work aimed at enhancing DPX bioavailability via the formulation of instantly dissolving buccal films comprising a pH modifier and a hydrophilic cyclodextrin. Tartaric acid and hydroxypropyl beta-cyclodextrin were selected as dual solubilizing agents based on the screening study. 32 factorial design was employed for the formulation and optimization of DPX films. Statistical analysis revealed that hydroxypropyl methyl cellulose E5: maltodextrin ratio and propylene glycol concentrations have significant effects on mechanical properties, percent DPX dissolved after 5 min, and in vivo mouth dissolving time at P < 0.05. The optimized film [HPMC E5: MDX, 1:1 and 1% PG] showed no significant change of properties or drug dissolution upon storage at 40 °C/75% RH for a period of 3 months. In addition, the optimized film showed significantly enhanced absorption relative to the oral reference tablet. Therefore, the optimized film could be considered a promising delivery system for DPX with expected improved patient compliance and enhanced pharmacokinetic performance.

中文翻译：

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通过配制具有酸性pH调节剂和亲水性环糊精的速溶颊膜，可增强盐酸达泊西汀的药代动力学性能：因子分析，体内和体外评估。

立即溶解的颊膜由于其易于管理和克服药物的肝首过效应的能力而受到关注。盐酸达泊西汀（DPX）由于明显的肝脏首过代谢而具有较低的口服生物利用度。此外，DPX是一种弱碱性药物，其pH依赖性溶解度可能会限制其在人体中性液中的溶解。为了克服这些挑战，这项工作旨在通过配制包含pH调节剂和亲水性环糊精的速溶颊膜来提高DPX的生物利用度。根据筛选研究，选择酒石酸和羟丙基β-环糊精作为双重增溶剂。32阶乘设计用于DPX膜的配方和优化。统计分析表明，羟丙基甲基纤维素E5：麦芽糊精比率和丙二醇浓度对机械性能，5分钟后溶解的DPX百分比以及体内口溶时间为P <0.05都有显着影响。优化的薄膜[HPMC E5：MDX，1：1和1％PG]在40°C / 75％RH下存储3个月后，其性能或药物溶解度均无明显变化。另外，相对于口服参考片剂，优化的膜显示出显着增强的吸收。因此，优化的薄膜可以被认为是DPX的有希望的输送系统，有望改善患者的依从性并增强药代动力学性能。5分钟后DPX溶解百分率，体内口腔溶解时间P ＜0.05。优化的薄膜[HPMC E5：MDX，1：1和1％PG]在40°C / 75％RH下存储3个月后，其性能或药物溶解度均无明显变化。另外，相对于口服参考片剂，优化的膜显示出显着增强的吸收。因此，优化的薄膜可以被认为是DPX的有希望的输送系统，有望改善患者的依从性并增强药代动力学性能。5分钟后DPX溶解百分比，体内口腔溶解时间为P <0.05。优化的薄膜[HPMC E5：MDX，1：1和1％PG]在40°C / 75％RH下存储3个月后，其性能或药物溶解度均无明显变化。另外，相对于口服参考片剂，优化的膜显示出显着增强的吸收。因此，优化的薄膜可以被认为是DPX的有前途的输送系统，有望改善患者的依从性并增强药代动力学性能。相对于口服参考片剂，优化的膜显示出显着增强的吸收。因此，优化的薄膜可以被认为是DPX的有希望的输送系统，有望改善患者的依从性并增强药代动力学性能。相对于口服参考片剂，优化的膜显示出明显增强的吸收。因此，优化的薄膜可以被认为是DPX的有前途的输送系统，有望改善患者的依从性并增强药代动力学性能。