Abstract Aim: The aim of this work was to develop buccoadhesive tablets for the systemic delivery of duloxetine HCl (DXT) using more soluble derivatives of β-cyclodextrin, i.e. hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) and to investigate enhanced cellular uptake of inclusion complexed drug. Materials and methods: Freeze dried and spray dried complexes of both cyclodextrin derivatives with DXT (1:1 molar) were prepared and characterized with DSC, FTIR, and PXRD techniques. C971 and PC, on the basis of swelling behavior, erosion and in vitro residence time, were selected for further study at different levels (−1, 0, +1) to optimize the formulation in terms of enhanced drug release and ex vivo permeation. Results: SBEβCD based complexes show more aqueous solubility of DXT (0.782 and 0.958 mM) and more complexation efficiency compared to HPβCD at 25 °C and 37 °C, respectively. Apparent stability constant was reported to be higher (1109.94 and 1693.25 M−1) for DXT-SBEβCD at 25 °C and 37 °C, respectively, than the corresponding values for DXT-HPβCD systems. Enhanced cellular uptake using fibroblast cells was revealed for complexed drug compared to free drug . Conclusion: Both cyclodextrin derivatives are able to enhance drug release and permeation in vitro and ex vivo.

中文翻译：

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环糊精衍生物对盐酸度洛西汀经口腔途径全身释放的影响

摘要 目的：这项工作的目的是开发使用更易溶的 β-环糊精衍生物，即羟丙基-β-环糊精 (HPβCD) 和磺丁基醚-β-环糊精 (SBEβCD) 全身给药盐酸度洛西汀 (DXT) 的颊黏贴片。并研究增强的包合物药物的细胞摄取。材料和方法：制备了两种环糊精衍生物与 DXT（1:1 摩尔）的冷冻干燥和喷雾干燥复合物，并用 DSC、FTIR 和 PXRD 技术表征。根据溶胀行为、侵蚀和体外停留时间，选择 C971 和 PC 进行不同水平（-1、0、+1）的进一步研究，以在增强药物释放和离体渗透方面优化配方。结果：基于 SBEβCD 的复合物显示出更高的 DXT 水溶性（0.782 和 0. 958 mM) 和更高的复合效率，分别与 25 °C 和 37 °C 下的 HPβCD 相比。据报道，DXT-SBEβCD 在 25 °C 和 37 °C 下的表观稳定性常数分别高于 DXT-HPβCD 系统的相应值（1109.94 和 1693.25 M-1）。与游离药物相比，复合药物显示出使用成纤维细胞增强的细胞摄取。结论：两种环糊精衍生物都能够增强体外和体外药物的释放和渗透。