Quality Control Core of Medicines and Correlates - NCQMC, Department of Pharmaceutical Sciences, Federal University of Pernambuco, Recife, PE, Brazil.
Postgraduate Program in Pharmaceutical Sciences, Pharmaceutical Sciences Institute, Federal University of Alagoas, Maceió, Alagoas, Brazil.
AAPS PharmSciTech. 2024 Sep 12;25(7):214. doi: 10.1208/s12249-024-02932-5.
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.
本研究旨在通过计算和热学研究、溶解度研究以及组合筛选技术评估奈韦拉平（NVP）与不同共晶形成剂（拉米夫定-3TC、柠檬酸-CAc 和尿素）形成共晶体系（CAM）的情况；此外，还开发和表征了合适的 NVP-CAM。采用淬冷法获得 NVP-CAM，并通过差示扫描量热法（DSC）、X 射线衍射法（XRD）、傅里叶变换红外光谱法（FTIR）和偏光显微镜法（PLM）进行表征，此外还在 pH6.8 下进行了体外溶解研究。筛选结果表明，NVP 与 3TC 之间存在分子间相互作用；NVP 与 CAc 之间也存在相互作用，验证了 NVP 熔融温度的偏移。由于氢键的存在，CAc 会影响 NVP 的平衡溶解度。DSC 热图谱表明，在共晶形成剂存在的情况下，NVP 的吸热峰减少并发生位移，表明化合物部分互溶。XRD 和 PLM 分析证实了非晶化的存在。与游离 NVP 相比，NVP-CAM 的体外溶解研究显示出溶解度和溶解效率的显著提高。组合使用筛选研究有助于开发稳定且无定形的 NVP-CAM，提高 NVP 的溶解度，使 CAM 成为联合抗逆转录病毒治疗的有前途的系统。
