Enhancing performance of dipyridamole solid dispersions via hydrophilic additives

Abstract

Background: Physiologically generated supersaturation and subsequent crystallization of a weakly basic drug in the small intestine leads to compromised bioavailability. Our previous study found(98) found that the combination of dypridamole, a poorly water-soluble basic drug, and Eudragit S100, a precipitation inhibitor, maintains supersaturation of drug at pH 6.8. The objective of this study was to investigate four plasticizer including PEG, GLY, MP and PP in term of their effects on the maintenance of drug supersaturation by Eugragit S100.Aim: Investigating the effect of 4 plasticizers; It includes polyethylene glycol, glycerin, methylparaben and propylparaben to maintain the supersaturation of dipyridamole by Odragit S100.Methods: The combination of Eu and plastisizers were prapered by rotary evaporation method and their performance were studied. Dissolution tests were conducted with a change of the medium from HCl solution (pH 1.2) to phosphate buffer (pH 6.8).Results: For all types of plastisizers, it was possible to detect the superior performance of Eu/plastisizer in supersaturation maintenance of DP as a function of plasticizer percentage compared to Eu alone but the hydrophobic plastisizers (MP and PP) exhibited the better performances than hydrophilic plastisizers (PEG and GLy). The combination of the Eu with plastisizers demonstrated a higher drug supersaturation level at higher plastisizer percentages. Lastly, dissolution results indicated the improvement effect of plastisizers on DP supersaturation manintanance by Eu and revealed that the type of plasticizer plays an essential role for this improvement.Conclusion: The dissolution test results showed that the effect of Odragit S100 in maintaining the supersaturation of dipyridamole by plasticizers increased significantly and the type of plasticizer played an important role in this increase.