Effect of the use of acidifiers on the crystallization of dihydroamidol from supersaturated state

Abstract

Introduction: poorly water soluble basic drugs are very sensitive to pH changes and following dissolution in the acidic stomach environment tend to precipitate upon gastric emptying, which leads to compromised or erratic oral bioavailability. Aim: In this work the inhibitory effect on Dipyridamole percipitation in buffer solution (pH=6.8) was evaluated using acidifires including Tartaric acid, Citric acid, Succinic acid and Adipic acid. Methods: Upon induction of supersaturation in buffer solution using a pH shift method and concentration of drug was assessed as a function of time. The area under the concentration-time curve values were calculated for each evaluated composition to provide a quantitative means of comparing the extent of supersaturation. Formulations containing drug and acidifiers were produced by solvent evaporation and were characterized using dissolution studies and characterized by FT-IR and differential scanning calorimetry. Results: Supersaturation in buffer solution (pH=6.8) was observed for Dipyridamole, but proved to be unstable due to fast precipitation. acidifier- mediated stabilizing effects on supersaturation were observed using Citric acid. Dissolution analysis revealed that using of DP-CA formulation functioned to improve dissolution performance of DP formulations by stabilizing supersaturated state of the drug. Interaction between drug and acidifier which was confirmed by FT-IR and DSC was necessary for supersaturation stabilization. Conclusion: From these findings, the addition of Citric acid and Tartaric acid in Dipyridamole formulation might be beneficial to enhance the dissolution and bioavailability of Dipyridamole.