Stability study of a new CDS prodrug of ethambutol
Rosangela Gonçalves Peccinini Principios Ativos Naturais e Toxicologia
São Paulo State University – UNESP
São Paulo, Brazil
Abstract:
A new ethambutol prodrug, using the Chemical Delivery System (CDS), was obtained in order to improve the access of the tuberculostatic agent to the Central Nervous System (CNS) for tuberculosis meningitis treatment. The prodrug presents a higher lipophilicity, what could increase the permeation through the blood-brain barrier. However, the compound might undergo chemical reactions such as chemical or enzymatic hydrolysis; if the liposolubility increases. The aim of this study was to evaluate the stability of the product in assays performed to mimetize physiologic situations, such as acid pH's (1.2), neutral pH's (7.4) and plasmatic enzymes action. This might hydrolyze the prodrug and increase decomposition before the delivery in the CNS. The compound was quantified by HPLC (Waters Alliance®) using UV detection at 256 nm and separated by Symmetry C18 column (5 µm, 4,6 x 250mm). The mobile phase was constituted by water:methanol:acetonitrile (20:20:60) at 0.8 ml/min flow rate. The biological samples had the compound extracted using NaOH 0,1M and ethyl acetate as the extracting solvent. The ethambutol prodrug demonstrated stability in different pHs in the chemical assays, and under the action of plasmatic enzymes, which suggests that the prodrug will have reduced decomposition before achieving the target organ.
Keywords: Chemical Delivery System; Tuberculosis Meningitis; Ethambutol prodrug; hydrolysis
