Development and Evaluation of Polymeric Mixed Micelles Prepared using Hot-Melt Extrusion for Extended Delivery of Poorly Water-Soluble Drugs

The poor aqueous solubility is a well-recognized restriction for the clinical application of many drug molecules. Micelles delivery system provides a promising strategy for the solubility enhancement of hydrophobic drugs. This study developed and evaluated different polymeric mixed micelles prepared using hot-melt extrusion coupled hydration method to improve the solubility and extend the release of the model drug ibuprofen (IBP). The physicochemical properties of the prepared formulations were characterized in terms of particle size, polydispersity index, zeta potential, surface morphology, crystallinity, encapsulation efficiency, drug content, in vitro drug release, dilution stability, and storage stability. Soluplus (R)/poloxamer 407, Soluplus (R)/poloxamer 188, and Soluplus (R)/TPGS mixed micelles had average particle sizes of 86.2 +/- 2.8, 89.6 +/- 4.2, and 102.5 +/- 3.13 nm, respectively with adequate encapsulation efficiencies of 80% to 92%. Differential scanning calorimetry studies confirmed that the IBP molecules were dissolved in the polymers in an amorphous state. The in vitro release results revealed that the IBP-loaded mixed micelles presented extended-release behavior compared to the free drug. In addition, the developed polymeric mixed micelles remained stable upon dilution and one-month storage. These results demonstrated that the hot-melt extrusion coupling hydration method could be a promising, effective, and environment-friendly manufacturing technique for the scale-up production of polymeric mixed micelles to deliver insoluble drugs.(c) 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.