Studying the compatibility of a metoclopramide-HCl–paracetamol mixture via IHCMC and establishing a validated RP-HPLC method for its determination in tablets

Abstract

Currently metoclopramide hydrochloride (MCP-HCl) and paracetamol (PCM) are co-formulated together in a tablet form, which is widely used in relief of painful migraine. The purpose of this work was to investigate the physicochemical compatibility of this co-mixture in the solid form and in different media as well. A highly selective and sensitive RP-HPLC method was established to quantify MCP-HCl and PCM in the presence of their degradation products. Chromatographic separation was achieved on a C-8 column using phosphate buffer, acetonitrile and methanol (40 : 15 : 10, v/v/v, pH 3) as a mobile phase at a flow rate of 0.5 mL min⁻¹ with UV detection at 220 nm. Isothermal Heat-Conduction Micro-Calorimetry (IHCMC) was used to investigate heat-flow caused by physico-chemical incompatibility. The method was linear within concentration ranges such as 20–80 μg mL⁻¹ and 10–70 μg mL⁻¹ for MCP-HCl and PCM, respectively. The LOD and LOQ of the method for determination of MCP-HCl and PCM were 0.501, 0.101, 1.67 and 3.39, respectively. Other analytical validation parameters such as accuracy, precision, selectivity and applicability of the method were evaluated using an external standard addition technique. The tablets containing MCP-HCl and PCM in the concentration ratio of 1 : 100 were analyzed by the method successfully via two concentration levels. Thermal analysis of solid mixtures of the drugs showed compatibility over short and long terms in contrast with their aqueous mixtures. So it is not recommended that this drug mixture be formulated in a liquid form.