New Insight into Acidifier-Induced Enhancement of Dissolution of Weakly Basic Drug, Dipyridamole

• Published in: Journal of pharmaceutical innovation 2023-12, Vol.18 (4), p.1626-1637
• Main Authors: Maghsoodi, Maryam, Asghari, Farshid, Nokhodchi, Ali
• Format: Article
• Language: English
• Subjects: Biochemical Engineering; Biomedical and Life Sciences; Biomedicine; Biotechnology; Industrial and Production Engineering; Original Article; Pharmacology/Toxicology
• ISSN: 1872-5120; 1939-8042
• DOI: 10.1007/s12247-023-09730-9

Objective Most studies regarding acidifiers focused on their role in improving the dissolution performance of a drug by altering the pH of the microenvironment. However, in the current research work, the impact of four different acidifiers (citric acid, tartaric acid, succinic acid, adipic acid) on the pH-induced precipitation behavior of dipyridamole, a model weakly basic drug, in the bulk dissolution medium with respect to improving the dissolution performance of the drug was studied. Methods The dipyridamole-acidifier formulations were prepared by using the rotary evaporation method. To study the dissolution behavior of the formulations, a pH-shift dissolution test from pH 1.2 to neutral pH 6.8 to simulate normal pH condition of the gastrointestinal tract, and the direct dissolution test at pH 6.8 to simulate an increased pH of the stomach was conducted. Results In the pH-shift-based dissolution test, for all formulations containing acidifiers, the improved concentration of dipyridamole was observed proportional to the precipitation inhibitory effect of acidifies. In the direct dissolution test, the incorporation of acidifiers in formulations improved the dissolution performance of dipyridamole, dependent on the type of acidifier. Conclusion From these results, the formulation of a weakly basic drug with an appropriate acidifier, as a simple way, appears to be a promising technique to enhance the dissolution performance of the drugs with less dependency on stomach pH.