Dual approach for concomitant monitoring of dissolution and transformation at solidstate. Mebendazole salts case study

Abstract

Solid state phenomena are relevant to the pharmaceutical industry since changes that take place during manufacture or storage of pharmaceutical formulations can affect critical properties of the products. Dissolution monitoring is a critical parameter for pharmaceutical solid forms since it is finally related to active bioavailability and activity (or side effects). Both solid-state and dissolution are closely correlated since dissolution performance usually depends of solid forms to be tested. However, unexpected transformation may occur when solid for take contact to dissolution media complicating the panorama. The dissolution behavior of MBZ C, MBZ·M and MBZ·HCl was studied by a dual characterization of the phenomena, dissolution and solid transformation. The monitoring of dissolution was carried out by employing UV on-line measurements; solid residues were withdrawn during the experiments and monitored at-line by ATR-FTIR spectroscopy. Chemometric method MCR-ALS was applied to deconvolute the corresponding FTIR spectra. Both salts were partially dissolved in dissolution medium showing higher dissolution profiles than form C. MBZ·M remaining solid immediately transforms to MBZ C, while that coming from MBZ·HCl undergoes a gradual conversion to form C after a pseudo-equilibrium phase (40–60 min). This results are on full accord with MBZ·HCl dissolution profile, that exhibits high concentrations up to the first 30 min and a gradual descent between 40 and 60 min. No transformations were observed in MBZ C suspended solid during the dissolution test. MBZ·M and MBZ·HCl improve the solubility of MBZ but both in contact with 0.1 M HCl convert to form C, MBZ·HCl being the salt most favored in terms of solubility and stability.