Taste-Masked Flucloxacillin Powder Part 1: Optimisation of Fabrication Process Using a Mixture Design Approach

Okhee Yoo; Sam Salman; Britta S von Ungern-Sternberg; Lee Yong Lim

doi:10.3390/ph16081171

Taste-Masked Flucloxacillin Powder Part 1: Optimisation of Fabrication Process Using a Mixture Design Approach

Pharmaceuticals (Basel). 2023 Aug 17;16(8):1171. doi: 10.3390/ph16081171.

Authors

Okhee Yoo¹, Sam Salman^{2

3}, Britta S von Ungern-Sternberg^{3

4

5}, Lee Yong Lim¹

Affiliations

¹ Pharmacy, School of Allied Health, University of Western Australia, Perth, WA 6009, Australia.
² Clinical Pharmacology and Toxicology Unit, PathWest Laboratory Medicine, Perth, WA 6009, Australia.
³ Medical School, The University of Western Australia, Perth, WA 6009, Australia.
⁴ Perioperative Medicine Team, Perioperative Care Program, Telethon Kids Institute, Perth, WA 6009, Australia.
⁵ Department of Anaesthesia and Pain Medicine, Perth Children's Hospital, Perth, WA 6009, Australia.

Abstract

It is extremely challenging to formulate age-appropriate flucloxacillin medicines for young children, because flucloxacillin sodium (FS) has a lingering, highly bitter taste, dissolves quickly in saliva, and requires multiple daily dosing at relatively large doses for treating skin infections. In this paper, we describe a promising taste-masked flucloxacillin ternary microparticle (FTM) formulation comprising FS, Eudragit EPO (EE), and palmitic acid (PA). To preserve the stability of the thermolabile and readily hydrolysed flucloxacillin, the fabrication process employed a non-aqueous solvent evaporation method at ambient temperature. Optimisation of the fabrication method using a mixture design approach resulted in a robust technique that generated stable and reproducible FTM products. The optimised method utilised only a single solvent evaporation step and minimal amounts of ICH class III solvents. It involved mixing two solution phases-FS dissolved in ethanol:acetone (1:4 v/v), and a combination of EE and PA dissolved in 100% ethanol-to give a ternary FS:EE:PA system in ethanol: acetone (3:1 v/v). Solvent evaporation yielded the FTMs containing an equimolar ratio of FS:EE:PA (1:0.8:0.6 w/w). The fabrication process, after optimisation, demonstrated robustness, reproducibility, and potential scalability.

Keywords: Eudragit EPO; flucloxacillin; mixture design; paediatric formulation; palmitic acid; taste-masked microparticles.

Grants and funding

This research was supported by an Australian Government Research Training Program (RTP) Scholarship. This research was also supported by funds bequeathed to the University of Western Australia by Athelstan John Henton Saw OBE MLC. O.Y. is funded by a Stan Perron Charitable Foundation People grant, grant number (2022/GR000990). B.S.v.U.-S. is partly funded by the Stan Perron Charitable Foundation (00058) and through a National Health and Medical Research Council Investigator Grant (2009322).