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

Sheng Feng; Ziru Zhang; Ahmed Almotairy; Michael A Repka

doi:10.1016/j.xphs.2023.06.007

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

J Pharm Sci. 2023 Nov;112(11):2869-2878. doi: 10.1016/j.xphs.2023.06.007. Epub 2023 Jun 14.

Authors

Sheng Feng¹, Ziru Zhang¹, Ahmed Almotairy², Michael A Repka³

Affiliations

¹ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, United States.
² Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, United States; Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, Al Madinah AlMunawarah, 30001, Saudi Arabia.
³ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, United States; Pii Center for Pharmaceutical Technology, The University of Mississippi, University, MS 38677, United States. Electronic address: marepka@olemiss.edu.

PMID: 37327994
DOI: 10.1016/j.xphs.2023.06.007

Abstract

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®/poloxamer 407, Soluplus®/poloxamer 188, and Soluplus®/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.

Keywords: Amorphous solid dispersion; Extended release; Hot-melt extrusion; Micellar solubilization; Polymeric mixed micelles; Scale-up production; Solubility; Soluplus®.