Cyclodextrin-water soluble polymer ternary complexes enhance the solubility and dissolution behaviour of poorly soluble drugs. Case example: Itraconazole

摘要: The aim of the present series experiments was to improve solubility and dissolution/precipitation behaviour a poorly soluble, weakly basic drug, using itraconazole as case example. Binary inclusion complexes with two commonly used cyclodextrin derivatives recently introduced derivative were prepared. Their dissolution compared that pure drug marketed formulation Sporanox®. Ternary prepared by addition Soluplus®, new highly water soluble polymer, during formation itraconazole/cyclodextrin complex. A solid dispersion made Soluplus® also studied control. Solid state analysis performed for all formulations powder X-ray diffraction (pX-RD) differential scanning calorimetry (DSC). Solubility tests indicated approaches, aqueous formed hydroxypropyl-β-cyclodextrin (HP-β-CD) or hydroxybutenyl-β-cyclodextrin (HBen-β-CD) proved be most favourable approaches. Whereas showed very poor dissolution, both these ternary resulted in fast extensive release test media. Using results experiments, newly developed physiologically based pharmacokinetic (PBPK) silico model applied compare vivo Sporanox® predicted performance promising from vitro studies. PBPK modelling bioavailability is likely increased after oral administration complex formulations, especially when formulated comprising HP-β-CD HBen-β-CD Soluplus®.