Synthesis, Optimization, and Evaluation of the Inclusion Complex of Ibuprofen‐Hydroxypropyl‐beta‐cyclodextrin: An in Vitro and in Silico Study“

Abstract

Ibuprofen is a widely-used non-steroidal anti-inflammatory drug, which belongs to class II of Biopharmaceutics classification system with low aqueous solubility and dissolution rate and bioavailability problems. This study was conducted to synthesis, optimization, and evaluation of the inclusion complex of ibuprofen-hydroxypropyl-beta-cyclodextrin to overcome the challenges. Complex of ibuprofen and hydroxypropyl-beta-cyclodextrin (HPβCD) was prepared by co-evaporation method in different ratios of solvents (methanol, ethanol, and distilled water were used as solvent systems). In order to find out the optimum solvent ratio, molecular dynamics simulations were performed by NAMD 2.9 software. Differential scanning calorimetry was applied to assess the complexes crystallinity and thermal behaviors. Also, Fourier transform infrared was used to monitor structural changes. Furthermore, the solubility and dissolution profiles of complexes were evaluated and compared. Complexation with HPβCD was able to reduce crystallinity and improve the thermal stability, water solubility, and dissolution profile of all synthesized complexes. HPβCD complexation using ethanol and water solvents in the ratio of 9 : 1 and 3 : 1, increased the aqueous solubility of ibuprofen by 1155 % and 874 %, respectively that was considered as the optimum approach. The results indicated that complexation with HPβCD may be of potential use for improving the ibuprofen dissolution rate and bioavailability.