Insights into the ethanol solvate form of clarithromycin

Abstract

Some polymorphic drugs may undergo solid-state transformations as a result of storage and manufacturing processes, which could have a significant impact on the performance characteristics of the drug. The present study was conducted as a strategy to provide information on clarithromycin polymorphs. The exhaustive characterization of solid form 0, an ethanol solvate, was performed starting with the development of a new synthesis route. The structural characterization was carried on by comparing the form 0 with the form II, the one currently used on the market. A variety of techniques, such as solid state nuclear magnetic resonance, X-ray powder diffraction, infrared spectroscopy, thermoanalytical methods and confocal microscopy, were used to identify the form 0. These studies revealed important intermolecular interactions, as well as certain spatial and morphological particularities. The biopharmaceutical properties including solubility in water and simulated gastric fluid, and microbiological performance were investigated. The physical stability under normal storage conditions during 15 months was examined, revealing a desolvation process and a subtle polymorphic transformation. The studies performed on the ethanol solvate of clarithromycin could prove to be a useful tool for assays used to ensure that the drug quality remains without changes in the final dosage product.