Influence of pharmaceutical excipients on stability of pramipexole dihydrochloride monohydrate in tablets

Abstract

The purpose of this study was to evaluate the effect of the method of excipients addition (intra-granularly or extra-granularly) and type of excipients on the stability of pramipexole dihydrochloride monohydrate (PRM) tablets. Corn starch, pre-gelatinized starch, dibasic calcium phosphate, microcrystalline cellulose or lactose anhydrous were used as excipients. PRM tablets were prepared by a wet granulation method and stability tests were performed at 40 °C/75 % RH, 60 °C or 80 °C. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) were used to characterize the physicochemical properties of PRM. While PRM raw material was inherently stable, decreased content and increased related substances were detected for PRM tablets. By incorporating pre-gelatinized starch with the drug intra-granularly, the most stable PRM tablet formulation was achieved. The results of XRD, SEM and EDS suggested that PRM was at the surface of granules with an amorphous state. In general, as the amorphous form is more reactive than the crystalline form, compatibility between PRM and the excipient plays an important role for drug stability in the tablet. Therefore, it is essential to select proper excipients to improve stability of PRM tablets prepared using the wet granulation method. ? 2013 The Korean Society of Pharmaceutical Sciences and Technology.