Taste-Masked Flucloxacillin Powder Part 2: Formulation Optimisation Using the Mixture Design Approach and Storage Stability

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

doi:10.3390/ph16081179

Taste-Masked Flucloxacillin Powder Part 2: Formulation Optimisation Using the Mixture Design Approach and Storage Stability

Pharmaceuticals (Basel). 2023 Aug 18;16(8):1179. doi: 10.3390/ph16081179.

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

Flucloxacillin is prescribed to treat skin infections but its highly bitter taste is poorly tolerated in children. This work describes the application of the D-optimal mixture experimental design to identify the optimal component ratio of flucloxacillin, Eudragit EPO and palmitic acid to prepare flucloxacillin taste-masked microparticles that would be stable to storage and would inhibit flucloxacillin release in the oral cavity while facilitating the total release of the flucloxacillin load in the lower gastrointestinal tract (GIT). The model predicted ratio was found to be very close to the stoichiometric equimolar component ratio, which supported our hypothesis that the ionic interactions among flucloxacillin, Eudragit EPO and palmitic acid underscore the polyelectrolyte complex formation in the flucloxacillin taste-masked microparticles. The excipient-drug interactions showed protective effects on the microparticle storage stability and minimised flucloxacillin release at 2 min in dissolution medium. These interactions had less influence on flucloxacillin release in the dissolution medium at 60 min. Storage temperature and relative humidity significantly affected the chemical stability of the microparticles. At the preferred storage conditions of ambient temperature under reduced RH of 23%, over 90% of the baseline drug load was retained in the microparticles at 12 months of storage.

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 Dr 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).