Some Formulation Properties of Lapachol, A Potential Oncolytic Agent of Natural Origin

Abstract

Lapachol is a naphthaquinone of natural origin with reported oncolytic activity. However, earlier antitumor studies were inhibited by inadequate blood levels, allegedly due to formulation difficulties.

This present study shows that water solubility is markedly influenced by pH, varying from 1.5 μg/mL at pH 4.0 to 5 mg/mL at pH 10.0.

Evaluation of mixed solvent systems demonstrated that up to 30 mg/mL could be dissolved in polyethylene glycol (PEG) 400. Aqueous PEG 400 solutions of lapachol were stable at refrigerator temperatures but deteriorated when exposed to light or autoclaving. Aqueous ethanol or propylene glycol are realistic alternative solvent systems for injectable lapachol solutions that may be sterilized by autoclaving.

Phosphatide stabilized triglyceride emulsions are broken down by lapachol, suggesting an interfacial interaction between the phosphatide and the lapachol in the aqueous phase.