The aim of this study was to develop new
dipyridamole (DP)
salts with pH-independent solubility for improving oral bioavailability under
hypochlorhydria.
Salt screening was carried out using nine counterions by the temperature gradient method. Six DP
salts were obtained, and there was marked improvement in dissolution behavior for all DP
salts in a neutral medium. Most DP
salts were stable under accelerated conditions. On the basis of the dissolution and stability data, DP tosylate (DP/TS) was selected as a promising DP
salt. The pharmacokinetics of DP and the promising DP
salt were assessed in normal rats and
omeprazole-treated rats as a hypochlorhydric model. After
oral administration of DP/TS (10 mg-DP/kg) in normal rats, enhanced DP exposures with increased C(max) and AUC₀₋₃ were observed compared with those with DP by ca. 2.8- and 1.7-fold, respectively. There was ca. 1 h delay of T(max) and ca. 62% reduction of AUC₀₋₃ for DP in
omeprazole-treated rats compared with those for DP in normal rats; however, oral absorption for DP/TS under
hypochlorhydria was almost identical to that in normal rats. The newly developed DP/TS might provide better therapeutic efficacy in clinical use for hypochlorhydric patients.