Stability of anti-HIV Agents in Suspension

Abstract

The establishment of anti-retroviral therapy has markedly improved the prognosis of patients with human immunodeficiency virus (HIV) infection. However, HIV encephalopathy and progressive multifocal leucoencephalopathy lead to swallowing difficulties, and anti-HIV agents must sometimes be administered via a feeding tube. A simple suspension method has recently been proposed in which an agent is dissolved and suspended in warm water at 55 °C prior to administration. To assess whether a simple suspension method of anti-HIV agents is feasible, the stability of these agents was studied in suspension. Single agents or combinations of two or more agents were suspended in warm water at 55, 60, 70, or 80 °C, and the percentage of active principle remaining was studied by HPLC-UV after 20 min. The results indicated that 95% or more of all of the agents remained. In addition, agents were suspended in warm water at 80 °C, the water was maintained at 80 °C, and the percentage of agents remaining was studied after 60 min. The results indicated that the percentage of remaining tenofovir disoproxil fumarate (TDF) decreased significantly (P<0.01) by 10% or more. HPLC-UV revealed an increase of peaks area that were thought to be decomposition products.
This study showed no decrease in the percentage of agent remaining that would present problems in terms of introducing a simple suspension method of that agent. However, the percentage of TDF remaining in hot suspension decreased significantly, suggesting the need to study thermal stability when examining the feasibility of a simple suspension method.