engleski

Inclusion complexes of praziquantel and β- cyclodextrin and its derivatives

Praziquantel (PZQ) is the primary drug of choice in the treatment of human schistosomiasis which is parasitic infection caused by trematode species belonging to the genus of Schistosoma. It is recognized as an essential drug and the first therapeutic option by WHO. According to The Biopharmaceutics Classification System, PZQ is classified as a Class 2 drug substance, meaning it possesses low aqueous solubility and high permeability. Cyclodextrins (CDs) are cyclic oligosaccharides and they can contain six (α- CD), seven (β-CD) or eight (γ-CD) glucose monomer units which are (α-1, 4)-linked in a ring formation. They are cone-shaped molecules with hydrophilic outer surface and lipophilic (hydrophobic) inner cavity. In the past couple of decades they have been intensively investigated for their drug- delivery ability since they are able to form water-soluble inclusion complexes with poorly soluble compounds. CDs (the host molecule) and the poorly soluble compounds (the guest molecule) usually form inclusion complexes of 1:1 stoichiometry.[1] Effect of β-cyclodextrin and its hydroxypropyl (HPβCD), methyl (MEβCD) and sulphobuthylether (SBEβCD) derivatives on PZQ solubility has already been studied, but quantitative determination of PZQ was performed using high performance liquid chromatography (HPLC).[2] The aim of this study is to prepare PZQ inclusion complexes with β-CD, HPβCD, SBEβCD and randomly methylated β-CD (RAMEB). Phase-solubility testing will be performed according to the existing Higuchi-Connors method.[3] According to this method, phase- solubility diagrams are constructed to evaluate total drug solubility changes with increasing CD concentration. For that reason, UV-Vis spectrophotometric method for quantitative determination of PZQ was developed and validated. Since PZQ is fluorescent compound, quantitative determination of PZQ will be performed by fluorescence spectroscopy as well. Key words: praziquantel, cyclodextrin, inclusion complex References: [1] T. Loftsson, M. D. Moya- Ortega, C. Alvarez- Lorenzo and A. Concheiro, J. Pharm. Pharmacol., 68, 544‒555 (2016). [2] M. Cugovčan, J. Jablan, J. Lovrić, D. Cinčić, N. Galić, M. Jug, J. Pharm. Biomed. Anal., 137, 42‒53 (2017). [3] T. Higuchi, K. A. Connors, Adv. Anal. Chem. Instr., 4, 117-212 (1965).

praziquantel ; cyclodextrin ; inclusion complex

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