Thermal characterization and kinetic study of the antiretroviral tenofovir disoproxil fumarate

Abstract

Tenofovir disoproxil fumarate (TDF) is an antiretroviral belonging to the class of nucleotide analog reverse transcriptase inhibitors, approved for the use against HIV/Aids and hepatitis B. The objective of this study was to evaluate the thermal compatibility and non-isothermal kinetic degradation of TDF with pharmaceutical adjuvants used in its tablet dosage form. TDF in binary mixtures with these excipients (BM) was prepared at 1:1 (mass%). Starting with thermoanalytical techniques (differential scanning calorimetry and thermogravimetric analysis/DTG) were select some BM with signs of interaction and complementary techniques of X-ray diffraction (XRD), infrared spectroscopy (IR) and kinetic degradation were used to elucidate the drug–excipient interactions. The purity of TDF was 98.28%, with the fusion peak at 117.53 °C followed by the main degradation event at 146.49 °C. The BM with lactose and magnesium stearate (MgS) were selected as promoted interaction with the drug based on the anticipation of the fusion peak of TDF, with a probable occurrence of a Maillard reaction between TDF and lactose. According to FTIR, these interactions were confirmed by an intermolecular hydrogen binding; however, the XRD analyses only indicate some loss of drug crystallinity in the BM profiles after the heating process. Kinetic degradation showed a kinetic reaction of first order, a variation of activation energy negligible for the BM TDF + MgS (5%) and a greater variation in its value for the formulation (15%) in relation to the isolated TDF, thus indicating a higher negative interference of the whole excipients to guarantee the thermal stability of TDF. This study provided detailed information on the interaction between TDF and the excipients composing the dosage form as a first study of thermal compatibility involving this drug that aims to guide in the delineation of other formulations containing this drug.