Stability behaviour of antiretroviral drugs and their combinations. 9: Identification of incompatible excipients

J Pharm Biomed Anal. 2019 Mar 20:166:174-182. doi: 10.1016/j.jpba.2019.01.009. Epub 2019 Jan 8.

Abstract

Incompatibility studies of antiretroviral drugs, viz., lamivudine (3TC), emtricitabine (FTC), abacavir sulfate (ABC), tenofovir disoproxil fumarate (TDF), zidovudine (ZDV), efavirenz (EFV) and nevirapine (NVP) were carried out in the presence of ten selected excipients, i.e., microcrystalline cellulose, lactose monohydrate, starch, magnesium stearate, sodium lauryl sulfate, sodium starch glycolate, croscarmellose sodium, colloidal silica, povidone K-30 and hydroxypropyl cellulose. Among all, ABC showed reaction with lactose monohydrate, resulting in the formation of two interaction products, while sodium lauryl sulphate enhanced the degradation of TDF. The interaction products of ABC-Lactose were separated by high performance liquid chromatography (HPLC) and subjected to liquid chromatography-high resolution mass spectrometry (LC-HRMS) studies for their characterization. One of the products was also isolated and subjected to 1D and 2D nuclear magnetic resonance (NMR) studies for structural confirmation. The toxicity of both was predicted using TOPKAT and ADMET™ software and compared to the drug.

Keywords: Abacavir sulphate; Characterization; Incompatibility; Interaction products; Lactose monohydrate; Toxicity.

MeSH terms

  • Animals
  • Anti-Retroviral Agents* / chemistry
  • Anti-Retroviral Agents* / metabolism
  • Anti-Retroviral Agents* / toxicity
  • Chromatography, High Pressure Liquid
  • Computer Simulation
  • Drug Interactions
  • Drug Stability
  • Excipients* / chemistry
  • Excipients* / metabolism
  • Excipients* / toxicity
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Biological*
  • Molecular Structure
  • Predictive Value of Tests
  • Tandem Mass Spectrometry

Substances

  • Anti-Retroviral Agents
  • Excipients