New Multicomponent Forms of the Antiretroviral Nevirapine with Improved Dissolution Performance

REVIGLIO, ANA L.; LINCK, YAMILA G.; RESENDE, JACKSON A. L. C.; CHOQUESILLO-LAZARTE, DUANE; COSTA, ROGERIA N.; CARDOSO, SIMONE G.; CARVALHO, ALEXANDRE M. G.; ROCHA, HELVÉCIO V. A.; CUFFINI, SILVIA L.; SIEDLER, SANA; MONTI, GUSTAVO A.; CHAVES, MARCELO H. C.; INFANTES, LOURDES

CRYSTAL GROWTH & DESIGN

AMER CHEMICAL SOC

Lugar: Washington; Año: 2019 vol. 20 p. 688 - 698

1528-7483

In the pharmaceutical area, some drugs exhibit physicochemical properties that adversely affect the formulation processes to bioavailability and its effectiveness. Nevirapine (NVP) is an antiretroviral drug that presents low aqueous solubility, which impacts directly in its bioavailability. Among all possible modifications, multicomponent crystals, such as cocrystals and eutectic compositions, have been successfully used to improve the solubility of drugs. In this work, the propensity of the formation of multicomponent systems of NVP with seven possible co-formers were predicted and tested: salicylic acid (SA), 3-hydroxybenzoic acid (3HBZC), 4-hydroxybenzoic acid (4HBZC), saccharin (SAC), theophylline (THEO), caffeine (CAF), and urea (URE). Results indicate that NVP-SA, NVP-SAC, NVP-3HBZC, and NVP-4HBZC are cocrystals, whereas NVP-THEO and NVP-CAF are eutectic materials, and NVP-URE is a solid physical mixture. A temperature-dependent disorder behavior was identified for NVP-SA cocrystal. Dissolution studies for the eutectic materials are reported, evidencing that these materials exhibit a significant increase in NVP dissolution kinetics.