Naslov
Biopharmaceutical characterization of praziquantel cocrystals andcyclodextrin complexes prepared by grinding

Autori
Cugovčan, Martina ; Jablan, Jasna ; Lovrić, Jasmina ; Cinčić, Dominik ; Galić, Nives ; Jug, Mario

Izvornik
Journal of pharmaceutical and biomedical analysis (0731-7085) 137 (2017); 42-53

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Praziquantel ; Grinding ; Cocrystal ; Cyclodextrin complex ; Chemical stability ; Dissolution ; In vitro permeability

Sažetak
TMechanochemical activation using several different co-grinding additives was applied as a green chem-istry approach to improve physiochemical and biopharmaceutical properties of praziquantel (PZQ).Liquid assisted grinding with an equimolar amount of citric acid (CA), malic acid (MA), salicylic acid(SA) and tartaric acid (TA) gained in cocrystal formation, which all showed pH-dependent solubilityand dissolution rate. However, the most soluble cocrystal of PZQ with MA was chemically unstable, as seen during the stability testing. Equimolar cyclodextrin complexes prepared by neat grinding withamorphous hydroxypropyl-ß-cyclodextrin (HPßCD) and randomly methylated ß-cyclodextrin (MEßCD)showed the highest improvement in drug solubility and the dissolution rate, but only PZQ/HPßCD productpresented an acceptable chemical and photostability profile. A combined approach, by co-grinding thedrug with both MA and HPßCD in equimolar ratio, also gave highly soluble amorphous product whichagain was chemical instable and therefore not suitable for the pharmaceutical use. Studies on Caco-2monolayer confirmed the biocompatibility of PZQ/HPßCD complex and showed that complexation didnot adversely affect the intrinsically high PZQ permeability (Papp(PZQ) = (3.72 ± 0.33) × 10−5cm s−1andPapp(PZQ/HPßCD) = (3.65 ± 0.21) × 10−5cm s−1 ; p > 0.05). All this confirmed that the co-grinding with theproper additive is as a promising strategy to improve biopharmaceutical properties of the drug.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA