engleski

Solubilization study of inclusion complexes of praziquantel with β-cyclodextrin and its derivatives by liquid chromatography

Praziquantel (PZQ) is an anthelmintic drug, effective against a broad range of trematodes and cistodes. It is a drug of choice in treatment of human schistosomiasis, a parasitic infection caused by trematode species of the genus Schistosoma. Due to its limited aqueous solubility and high permeability, it is classified as type II drug, according to the Biopharmaceutical Classification System. Cyclodextrins (CD) are cyclic oligosaccharides consisting of 6 (α-CD), 7 (β-CD), 8 (γ-CD) or more α-1, 4-linked glucopyranose units. The molecules are cone shaped with hydrophilic outer surface and lipophilic central cavity. Studies have shown that cyclodextrins can improve solubility and chemical stability of drugs with limited solubility by forming inclusion complexes of 1:1 stoichiometry. In the last decade, effects of cyclodextrins and their derivatives on improvement of solubility of drugs have been extensively researched, and some of these formulations can be found in commercially available pharmaceutical products. Although, study of effect of cyclodextrins on biopharmaceutical properties of PZQ already exists, only solid complexes were studied. Since structures of crystalline complexes can differ from those in solution, phase solubility studies in solution should also be researched. In this work we present effect of natural β- cyclodextrin and its hydroxypropyl (HP-β-CD), sulphobutylether (SBE-β- CD) and methyl (Me-β- CD) derivatives on PZQ solubility in aqueous media. The effect of cyclodextrins was studied according to method presented by Higuchi and Connors. Total solubility of PZQ in the presence of increasing concentration of cyclodextrins was determined by liquid chromatography. Phase solubility diagrams were constructed and stability constants as well as complexation efficacies were determined.

praziquantel, cyclodextrins, phase solubility, HPLC

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