Rifampicin Dissolution: Polymorphism or Crystal Defects

Abstract

The objective of this investigation was to study the effect of contact of rifampicin physical form with the dissolution medium. Solid-state characterization of the residues obtained from powder dissolution studies were conducted and found that rifampicin form II undergoes a conversion to form I or some other form at the crystal surface, which is attributed to crystal defects. The solid-state characterization studies were carried out by various physical methods. The phenomenon of polymorphism in most of the drugs is exploited to get the more soluble and hence the more bioavailable form. But, if there is a change in the polymorphic form after coming in contact with the dissolution medium, then the choice of the initial polymorphic form to be used in the drug product is of no concern. A distinct change was observed in thermogravimetric analysis (TGA), single differential thermal analysis (SDTA), and differential scanning calorimetry (DSC) thermograms of rifampicin form II before and after dissolution, whereas powder X ray diffraction (pXRD) patterns were almost indistinguishable, except for a change in intensity of some of the peaks and a shift in the peak corresponding to 100% relative intensity to a higher d-spacing value. The most plausible reason for this might be the change in polymorphic form only at the crystal surface. Rifampicin form II shows a surface transformation to either form I or some other form after coming in contact with the dissolution medium, indicating that the physical form of rifampicin is not stable upon contact with the aqueous environment.