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 the 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 metabolism. The aqueous solubility of PZQ was improved by forming inclusion complexes with alpha-, beta- and gamma-cyclodextrins (CDs). These complexes were assessed and confirmed by solubility analysis, Fourier transform infrared analysis, elemental analysis, differential scanning calorimetry and mass spectrometry. Dissolution of PZQ from the alpha-, beta- and gamma-CD complexes 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 optimum range for pharmaceutical use, suggesting that the preferred complex for further development would be a water-soluble beta-CD derivative.
School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand.gordon.becket@stonebow.otago.ac.nz
G
G
Becket
L J
LJ
Schep
M Y
MY
Tan
D000980:Antiplatyhelmintic Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D003198:Computer Simulation; D003505:Cyclodextrins / Q000737:chemistry*; D005079:Excipients; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011223:Praziquantel / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins
D000980:Antiplatyhelmintic Agents; D003505:Cyclodextrins; D005079:Excipients; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; D011223:Praziquantel; C031215:betadex; C023792:gamma-cyclodextrin; C032613:alpha-cyclodextrin