title: Solution-mediated phase transformation of different roxithromycin solid-state forms: Implications on dissolution and solubility.
abstract: The objective of this study was to describe the solid-state forms in which roxithromycin may exist and the significant influence of solution-mediated phase transformation on the dissolution and solubility behavior of these forms. Roxithromycin may exist as: Form I (monohydrate), Form II (amorphous), Form III (anhydrate) and a mixture of Forms I and III. Form III and Mixture I/III have not been reported previously, probably due to incomplete solid-state characterization or the use of a standard production method which consistently yielded the same solid-state form. Solution-mediated phase transformations of Forms II and III to the stable Form I were proved through dissolution studies and quantification of the phase proportions, as a function of time, utilizing XRPD. This study showed that pharmacopoeial identification methods for roxithromycin do not allow accurate identification of the different solid-state forms. The various forms differed significantly in terms of dissolution profiles, which could have a marked influence on bioavailability and performance of the final dosage form. It was demonstrated that solvent replacement, during dissolution testing, masks the characteristic profile usually obtained with a metastable form undergoing solution-mediated transformation. Finally, we propose that peak dissolution concentrations should be used to give a more exact indication of the aqueous solubility enhancement ratio obtained with metastable forms of APIs.
authors.affiliation: Center of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom Campus, 2520, South Africa. Marique.Aucamp@nwu.ac.za
authors.forename: Marique
authors.initials: M
authors.lastname: Aucamp
authors.forename: Nicole
authors.initials: N
authors.lastname: Stieger
authors.forename: Neil
authors.initials: N
authors.lastname: Barnard
authors.forename: Wilna
authors.initials: W
authors.lastname: Liebenberg
mesh_terms: D002626:Chemistry, Pharmaceutical; D044367:Phase Transition; D015575:Roxithromycin / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D015575:Roxithromycin