Preparation and characterization of dipyridamole solid dispersions for stabilization of supersaturation: effect of precipitation inhibitors type and molecular weight

Abstract

Dipyridamole (DPL) is a weakly basic BCS class II drug which precipitates upon entering into intestine leading to pH dependant and variable absorption. Thus, research envisaged focuses on developing formulations that maintain supersaturation following upon acid to neutral pH transition. In an endeavor to accomplish the objective, solid dispersion (SD) with hydroxypropylmethyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) was prepared by a quench cooling method. The three molecular weight grades of HPMC (HPMC E5, HPMC E15 and HPMC E50) and two molecular weight grades of PVP (PVP K30 and PVP K90) were investigated to observe effect of increasing molecular weight on stabilizing DPL supersaturated solutions. Equilibrium solubility studies revealed increase in solubility with both HPMC and PVP with greater benefit from HPMC. In vitro supersaturated dissolution results demonstrated that HPMC formulations provided greater degree and extent of supersaturation as compared to PVP formulations. The formulation with HPMC E50 provided maximum stabilization to supersaturation upon acid to neutral pH transition. Moreover, the effect of increase in molecular weight was more pronounced in HPMC rather than PVP. Stronger interactions were observed for DPL with HPMC, while no interaction was observed with PVP which was evident from Fourier transform infra-red studies. Differential scanning calorimetry and powder X-ray diffraction studies revealed the amorphous state of DPL in SD.

• Hydroxylpropylmethyl cellulose
• povidone
• quench cooling
• solid dispersion
• supersaturation

Acknowledgements

We greatly appreciate the Metallurgical Department, Faculty of Technology and Engineering, The M.S. University of Baroda, Vadodara, Gujarat, India for skillful assistance and providing PXRD testing facility in this study, respectively. The authors are grateful to the industries that provided respective gift samples.

Declaration of interest

The authors confirm that this article content has no conflicts of interest. One of the authors, Mr. Chintan Vora is highly grateful to the University Grants Commission, New Delhi, Government of India, for providing financial assistance in the form of research fellowship.