Improvement of the in vitro dissolution of praziquantel by complexation with alpha-, beta- and gamma-cyclodextrins

Although praziquantel (PZQ) is the primary drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery via the oral route. In spite of its poor solubility, PZQ is well absorbed across t he gastrointestinal tract, but large doses are required to achieve adequate concentrations at the target sites. Improving the solubility would enable the parenteral route to be used, thereby avoiding significant first pass me tabolism. The aqueous solubility of PZQ was improved by forming inclusion c omplexes with alpha-, beta- and gamma-cyclodextrins (CDs). These complexes were assessed and confirmed by solubility analysis, Fourier transform infra red analysis, elemental analysis, differential scanning calorimetry and mas s spectrometry. Dissolution of PZQ from the alpha-, beta- and gamma-CD comp lexes was 2.6-, 5- and 8-fold greater, respectively, than that of the pure drug. However, only the beta-complex had a stability constant in the optimu m range for pharmaceutical use, suggesting that the preferred complex for f urther development would be a water-soluble beta-CD derivative. (C) 1999 Pu blished by Elsevier Science B.V. All rights reserved.