Evaluation of the effect of some Eudragits on dissolution of dipyridamole solid dispersion formulations

Abstract

Background: 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: The purpose of this study was First, to identify excipients which effectively inhibit precipitation of Dipyridamole (DP). Second, to test the feasibility of ternary formulation strategies Methods: The effectiveness of Eudragits (Eu) E100, L100, L100-55, RL100 and RS100 in inhibition of drug precipitation were evaluated. pH-modifier technology employing an appropriate acidifier, tartaric acid (Ta), or solid dispersion technology using enteric polymer, Eudragit L100-55 were used to improve the dissolution rate of drug in neutral solution, while an effective inhibitor excipient, was added to inhibit the drug precipitation. Formulations were produced by solvent evaporation and characterized by FT-IR and differential scanning calorimetry. Dissolution experiments were carried out in phosphate buffer (pH=6.8) under non-sink conditions. Results: The results indicated that Eudragit E100, among the excipients investigated, inhibited drug precipitation the most. Dissolution results revealed that addition of Eudragit E100 to DP:Eu L100-55 formulations resulted in impaired dissolution profile, probably owing to the low solubility of Eudragit E100 at neutral pH. In contrast, inclusion of Eudragit E100 into DP:Ta formulations exhibied not only stability to precipitation but also higher concentration level of drug. FT-IR analysis demonstrated that there might be ionic interaction between tartaric acid and Eudragit E100 probably leading to the improved dissolution of Eudragit E100 in this formulation. Conclusion: According to these results, it may be concluded that acidifier (Tartaric acid) was indeed more effective compared with enteric polymer in enhancing drug dissolution in combination with Eudragit E100.