Exploring Co-Amorphous Formulations Of Nevirapine: Insights From Computational, Thermal, And Solubility Analyses

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-09-12 DOI:10.1208/s12249-024-02932-5

Kayque Almeida dos Santos, Luíse Lopes Chaves, Daniela Nadvorny, Mônica Felts de La Roca Soares, José Lamartine Soares Sobrinho

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Abstract

This study aimed to assess the formation of nevirapine (NVP) co-amorphs systems (CAM) with different co-formers (lamivudine—3TC, citric acid—CAc, and urea) through combined screening techniques as computational and thermal studies, solubility studies; in addition to develop and characterize suitable NVP-CAM. NVP-CAM were obtained using the quench-cooling method, and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and polarized light microscopy (PLM), in addition to in vitro dissolution in pH 6.8. The screening results indicated intermolecular interactions occurring between NVP and 3TC; NVP and CAc, where shifts in the melting temperature of NVP were verified. The presence of CAc impacted the NVP equilibrium solubility, due to hydrogen bonds. DSC thermograms evidenced the reduction and shifting of the endothermic peaks of NVP in the presence of its co-formers, suggesting partial miscibility of the compounds. Amorphization was proven by XRD and PLM assays. In vitro dissolution study exhibited a significant increase in solubility and dissolution efficiency of NVP-CAM compared to free NVP. Combined use of screening studies was useful for the development of stable and amorphous NVP-CAM, with increased NVP solubility, making CAM promising systems for combined antiretroviral therapy.

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探索奈韦拉平的共无定形制剂：计算、热学和溶解度分析的启示

本研究旨在通过计算和热研究、溶解度研究等综合筛选技术，评估奈韦拉平（NVP）与不同共形物（拉米夫定-3TC、柠檬酸-CAc 和尿素）形成的共形物体系（CAM）；此外，还旨在开发和表征合适的 NVP-CAM。采用骤冷法获得了 NVP-CAM，并通过差示扫描量热仪（DSC）、X 射线衍射仪（XRD）、傅立叶变换红外光谱仪（FTIR）和偏振光显微镜（PLM）对其进行了表征，此外还在 pH 值为 6.8 的条件下进行了体外溶解。筛选结果表明，NVP 和 3TC、NVP 和 CAc 之间发生了分子间相互作用，NVP 的熔化温度发生了变化。由于氢键的作用，CAc 的存在影响了 NVP 的平衡溶解度。DSC 热图显示，NVP 的内热峰在共形成物存在时有所降低和移动，这表明化合物具有部分混溶性。XRD 和 PLM 检测证明了其非晶化现象。体外溶解研究表明，与游离 NVP 相比，NVP-CAM 的溶解度和溶解效率均有显著提高。综合利用筛选研究有助于开发出稳定的无定形 NVP-CAM，并提高了 NVP 的溶解度，使 CAM 成为有希望用于联合抗逆转录病毒疗法的系统。

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