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

• Published in: AAPS PharmSciTech Vol. 25; no. 7; p. 214
• Main Authors: dos Santos, Kayque Almeida, Chaves, Luíse Lopes, Nadvorny, Daniela, de La Roca Soares, Mônica Felts, Sobrinho, José Lamartine Soares
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 12-09-2024
• Subjects: Anti-HIV Agents - chemistry; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calorimetry, Differential Scanning - methods; Chemistry, Pharmaceutical - methods; Drug Compounding - methods; Hydrogen Bonding; Lamivudine - chemistry; Nevirapine - chemistry; Pharmacology/Toxicology; Pharmacy; Research Article; Solubility; Spectroscopy, Fourier Transform Infrared - methods; X-Ray Diffraction - methods; solubility; biopharmaceutical classification system (BCS); HIV; co-amorphous
• ISSN: 1530-9932; 1530-9932
• 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.
Graphical Abstract