Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug

摘要

The study elucidated the combined effect of the formulation parameters (the relative contents of the copolymer (poloxamer 407 (P407)), the cosolvent (isopropyl alcohol), and the hydrophobic drug (ibuprofen)) on gelation, applicative properties, drug solubilization capacity and release kinetics of the P407 aqueous solutions under the common conditions of storage and topical administration. The presence of ibuprofen at a therapeutic concentration of 5% enhanced the increase in micellar volume fraction and allowed the gelation of the liquid solutions at P407 concentrations >= 15%. Light microscopy, DSC analysis, and theological measurements pointed that P407 gels with 15-20% of the copolymer enabled controled precipitation of amorphous ibuprofen particles (<= 100 mu m) in perimicellar microchannels, while gels with 25-30% of P407 as well as increased relative content of the cosolvent in perimicellar aqueous phase, had capacity for complete ibuprofen solubilization. The dissolution of the drug partides during the in vitro drug release test, maintained the drug concentration gradient between the perimicellar microchannels and the acceptor medium allowing diffusion-based sustained drug release up to 12 h. The gels with completely solubilized drug notably decrease drug release rate and the cumulative amount of the drug released. Harmonization of the investigated formulation parameters was critical to the formulation of P407 gels that could be promising drug delivery systems for sustained percutaneous delivery of the hydrophobic model drug ibuprofen with reduced frequency of administration and improved patient compliance. (C) 2020 Elsevier B.V. All rights reserved.