Interaction and compatibility studies of efavirenz with pharmaceutical excipients

Abstract

Although excipients have traditionally been thought of as being inert, experience has showed interaction between them and the drugs; therefore, is very useful the knowledge about potential physical and chemical interactions. The compatibility of efavirenz with the excipients: sodium lauryl sulfate, spray dried lactose, hydroxypropylcellulose, magnesium stearate, microcrystalline cellulose and croscarmellose sodium were studied. X-ray powder diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FT-IR), Raman spectroscopy (RS) and Differential scanning calorimetry (DSC) were used as screening techniques. DSC curves of binary mixtures were quite different than efavirenz raw material, suggesting strong interaction and/ or even chemical reactions between efavirenz and excipients with temperature increasing. However, FT-IR, XRPD and RS showed that no interaction and/ or even chemical reaction between efavirenz and excipients occurred at room temperature. Efavirenz is one non-nucleoside reverse transcriptase inhibitor (NNRTI), used in the High Activity Antiretroviral Therapy (HAART) for the treatment of human immunodeficiency virus type 1 infection (HIV-1). This Active Pharmaceutical Ingredient (API) has more than one crystalline form, which may have implications for its behavior during production and also for its in vivo performance. XRPD, DSC, Scanning Electron Microscopy (SEM) and Intrinsic Dissolution Rate (IDR) were used in the solid-state characterization of efavirenz and was determined that the raw material used corresponds with Form I and maintains its crystal structure during the study. IDR indicated that bioavailability problems may arise because of drug-dependent dissolution.