SOLID-STATE STABILITY AND SOLUBILITY DETERMINATION OF CRYSTALLINE FORMS OF MOXIFLOXACIN HYDROCHLORIDE

Objective: This study aims to evaluate possible crystalline changes that can occur with MOX under the influence of temperature and relative humidity (RH) as well as to determine the relative solubility of the observed crystalline forms. Methods: Thermoanalytical methods with the support of non-thermal analysis such as X-ray powder diffraction and infrared spectroscopy were used for testing structural changes of Moxifloxacin hydrochloride (MOX) stored under four different conditions. Additionally, relative solubilities of the observed crystalline forms were determined by the shake-flask method. Results: After storage for 1 mo at 0 % relative humidity (RH) and 40 % RH, MOX remained with crystal structure unchanged and shown to have a good physical stability at these conditions. However, when the drug was stocked for 1 mo at 90 % RH and 75 %, a hydrated crystalline form was identified in both conditions. In the solubility assay, it was observed that the hydrated form is less soluble that initial MOX. Conclusion: Pharmacotechnical wet processes are not be recommended for the pharmaceutical production of this drug because solvent granulation and drying conditions from processing provides a favorable environment for the transition of crystalline forms. According to DSC, TG, PXRD, HPLC and FT-IR results, they showed good correlation with each other and ensure reliable interpretation of solid form stability studies. Moreover, these findings suggest that stability studies of a polymorphism associated with the evaluation of relative solubility are essential for a stable formulation development and to choose between dry or wet granulation processes.