Structure determination of NVP-AS co-crystal at different temperatures

GARRO LINCK, YAMILA; CARVALLO, ALEXANDRE M. G. ; CUFFINI, SILVIA; COSTA, ROGERIA; REVIGLIO, ANA LUCÍA; JACKSON, ANTÕNIO LAMOUNIER CAMARGO; SIEDLER, SANA; MONTI, GUSTAVO; ROCHA, HELVÉTICO VINÍCIUS ANTUNES

Foz do Iguaçu

Conferencia; 41a Reunião Anual da Sociedade Brasileira de Química; 2018

Sociedade Brasileira de Química

Co-crystallization is a strategy frequently used in pharmaceutical area to improve drug properties. 1,2 Nevirapine (NVP) is an antiretroviral drug that presents low solubility, which implies in low bioavailability and difficulties in formulation process. Based on this, different strategies are applied to obtain co-crystals of NVP. A pharmaceutical co-crystal is a crystalline structure formed between an active pharmaceutical ingredient (API) and another molecule pharmaceutically acceptable. The crystalline structure of NVP-salicylic acid (NVP-SA) had already been reported in the literature at low temperature. 3 This co-crystal was obtained by our group and differences were observed in the crystalline phases at room and low temperature (figures 1 and 2). X-Ray diffraction (XRD) experiments using synchrotron radiation source (XRD1 - LNLS) 4 (figure 3), thermal analysis and solid-state Nuclear Magnetic Resonance (ss-NMR) were used to characterize these materials. A study was conducted in order to determine the structures and identify the behavior of this co-crystal from room temperature to 100K. At room temperature, SA molecule is located on an inversion center, which allows describe two positions of this molecule in occupational disorder. However, when cooling is carried out, the molecule is stabilized in one position, inducing the loss of the symmetry center located in the SA molecule. This allows to describe the phase transition in the co-crystal.