Suspensions of antibiotics in self-emulsifying oils as a novel approach to formulate eye drops with substances which undergo hydrolysis in aqueous environment
The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil.
Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations.
The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.
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Materials
Cefuroxime sodium and VAN hydrochloride in the form of powder for injection were purchased from MIP-Pharma (Chephasaar, St. Ingbert, Germany). Polyoxyethylene sorbitan monolaurate (Tween 20) was purchased from Sigma-Aldrich (Steinheim, Germany), sorbitan monooleate (Span 80) from Fluka (Buchs, Switzerland), fractionated coconut oil (Miglyol 812) from Caesar & Loretz (Hilden, Germany), castor oil from Fagron (Kraków, Poland) and olive oil (Davalia oil from Aria Worldwide, Barcelona, Spain). Sodium citrate was obtained from Stanlab (Lublin, Poland).
All chemicals and solvents used for chromatographic analysis were of an analytical grade and were purchased from Avantor (Gliwice, Poland) or Sigma-Aldrich (Steinheim, Germany). Purified water was produced in-house with Elix 3 Millipore system (Bedford, MA).
Katarzyna Krzeminska, Malgorzata Sznitowska, Magdalena Wroblewska, Eliza Wolska & Katarzyna Winnicka (2024) Suspensions of antibiotics in self-emulsifying oils as a novel approach to formulate eye drops with substances which undergo hydrolysis in aqueous environment, Drug Delivery, 31:1, 2372279, DOI: 10.1080/10717544.2024.2372279