Sefiksimin Düşük Çözünürlük ve Permeabilitesinin Siklodekstrin Kompleksleri Kullanılarak Artırılması Üzerine Çalışmalar

Abstract

Cefixime(SEF) is a wide spectrum antibiotic that is included in the third generation cephalosporins group. Its oral bioavailability is reported to be 40 %. Cyclodextrins have the ability to interact with poorly water-soluble drugs resulting an increase in their apparent water solubility. It is also known that cyclodextrin complexation enhances oral bioavailability of poorly soluble drugs. Thus, it was aimed to design and develop cyclodextrin complexes containing SEF to improve aqueous solubility, permeability and oral bioavailability. In this study, using five different cyclodextrin derivatives, SEF's inclusion complexes were prepared by two different preparation methods which are kneading and coprecipitation/colyophilisation methods and resulting complexes then physicochemically characterized. Studies showed that the optimum results were obtained by kneading method and HP-β-CD. Tablet formulations were developed using SEF: HP-β-CD and SEF: M-β-CD kneaded complex and dissolution studies were carried out for both inclusion complexes and tablet formulations. Results of the dissolution studies also showed that complexation with cyclodextrins increased SEF dissolution rates significantly. In vitro permeability studies for SEF and SEF:CD inclusion complexes using Caco-2 cell culture model, indicates that cyclodextrin complexation also helps improve in vitro permeation of SEF increasing the drug's apparent permeability constant. Thus, it seems to be a promising solution for improving SEF's poor oral bioavailability. Both dissolution and phase solubility studies appear to confirm that among CD derivatives HP-β-CD and among complexation methods kneading method yield optimum data for cefixime.