Effect of cyclodextrin complexation on the aqueous solubility and solubility/dose ratio of praziquantel.
Praziquantel (PZQ), the primary drug of choice in the treatment of schistosomiasis, is a highly lipophilic drug that possesses high permeability and low aqueous solubility and is, therefore, classified as a Class II drug according to the Biopharmaceutics Classification System (BCS). In this work, beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were used in order to determine whether increasing the aqueous solubility of a drug by complexation with CDs, a BCS-Class II compound like PZQ could behave as BCS-Class I (highly soluble/highly permeable) drug. Phase solubility and the kneading and lyophilization techniques were used for inclusion complex preparation; solubility was determined by UV spectroscopy. The ability of the water soluble polymer polyvinylpyrolidone (PVP) to increase the complexation and solubilization efficiency of beta-CD and HP-beta-CD for PZQ was examined. Results showed significant improvement of PZQ solubility in the presence of both cyclodextrins but no additional effect in the presence of PVP. The solubility/dose ratios values of PZQ-cyclodextrin complexes calculated considering the low (150 mg) and the high dose (600 mg) of PZQ, used in practice, indicate that PZQ complexation with CDs may result in drug dosage forms that would behave as a BCS-Class I depending on the administered dose.
Maragos
Stratos
S
Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, National & Kapodistrian University of Athens, Athens, 15771, Greece.
Archontaki
Helen
H
Macheras
Panos
P
Valsami
Georgia
G
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000871:Anthelmintics / Q000737:chemistry*; D002138:Calibration; D004355:Drug Stability; D004356:Drug Storage; D011223:Praziquantel / Q000737:chemistry*; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000871:Anthelmintics; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011223:Praziquantel; C031215:betadex