Publication

Abstract : Olaparib (OLA), a biopharmaceutical class IV drug, suffers from limited oral bioavailability owing to poor solubility. In the present study, we explore the potential of cyclodextrin (CD) complexation for the drug candidate OLA, with the amalgamation of in silico, in vitro and prospective in vivo application in the improvement of pharmacokinetic properties. The current work articulates the incorporation of molecular dynamic studies to describe in situ complexation with in-depth insights on structure-elucidation using density function theory (DFT) and molecular dynamics. Spontaneous complexation was observed within 100 ns interaction which was evident from the binding energies during simulation studies. In silico elucidation approach has been correlated with 22.33-fold enhancement in aqueous phase solubility. Pharmacokinetic studies revealed 1.7-fold and 1.56-fold enhancement in AUC0-∞ and Cmax compared to free OLA. These results convey the successful amalgamation of in silico and in vitro tools towards in vivo pharmaceutical applications.