Thermal analysis of a drug-polymeric excipient solid system

Abstract

Differential scanning calorimetry has been applied to the study of the solid system crosslinked polyvinylpyrrolidone/trimethoprim.Different results have been systematically obtained on co-ground and not co-ground mixtures, suggesting some type of interaction to take place between components as a consequence of co-grinding.A simple phenomenological model of the interaction is proposed, which quite satisfactorily agrees with thermal data, It is well-known that drug-excipient interactions can deeply influence the technological and biopharmaceutical properties of solid dosage forms. Thermal analysis and particularly microcalorimetric differential techniques are often employed to evidence such interactions [1,2].Cross-linked polyvinylpyrrolidone (PVP-XL)i is an amorphous insoluble polymer widely used as a disintegrating agent and binder for tablets [3,4] and for the preparation of molecular dispersions [5,6].Trimethoprim (TMP), whose thermal and structural properties were extensively investigated by some of us [7,8], is a chemotherapeutic agent commonly used as antifolate drug in combination with sulfonamides [9].A preliminary investigation of the thermal behaviour of mixtures of PVP-XL and TM P evidenced deep changes in thermal profiles of ground mixtures with respect to those of the pure components, which were ascribed to possible interactions between TMP and PVP-XL [10]. For a better understanding and characterization of such interactions a more detailed DSC study has been undertaken on the system PVP-XL/TMP, whose results are here reported.It will be shown that a simple phenomenological model of the interaction can be proposed which quite satisfactorily agrees with thermal data.