Formulations of dipyridamole with Tartaric acid as a pH-modifier and Eudragit E as a precipitation inhibitor for improved dissolution

Abstract

Background: Making suitable and optimal formulations of drugs with low solubility is one of the concerns of pharmaceutical science.Poorly water-soluble basic drugs are sensitive to pH changes and following dissolution in the acidic environment of stomach tend to precipitate upon gastric emptying, which leads to compromised or erratic oral bioavailability.Aim: Optimizing the ratio of excipient and dipyridamole (DP) formulations to obtain maximum drug dissolution.Methods: Physical mixtures containing tartaric acid (pH modifier) and eudragit polymer E100 (precipitation inhibitor) were used to improve the dissolution rate of dipyridamole. Dissolution tests were performed in acidic medium (pH = 1.2) and phosphate buffer (pH = 6.8) to simulate the gastrointestinal tract under non-sink conditions, respectively.Results: The results of dissolution test and FT-IR spectra showed that tartaric acid maintained supersaturation for a considerable period of time by lowering the pH of the medium and possibly interacting with the drug. Eudragit E100 also inhibits dipyridamole precipitation by interacting with the drug. Simultaneous presence of tartaric acid and Eudragit in the formulation due to the effect of pH change by tartaric acid on the particle size of Eudragit and the interaction of tartaric acid and Eudragite, resulting in ionization of Eudragit causes a synergistic effect and greatly increases the solubility of dipyridamole in the alkaline medium.Conclusion: According to the results, the use of tartaric acid and Eudragit E100 in the three-component formulation of dipyridamole can improve the dissolution of the drug, maintain the high concentration and possibly increase the bioavailability of this drug. Therefore, the combination strategy of acidifier as dissolution enhancer and eudragit E100 as inhibitor of drug deposition resulted in achieving higher concentrations of drug in the dissolution medium.