Solid lipid microparticles (SLM) can be presented as liquid suspension or spray-dried powder. The main challenge in SLM technology is to precisely determine the location of the active substance (API) in the different compartments of the formulation and its changes during SLM processing. Therefore, the purpose of the research was to assess the distribution of the API and to investigate the nature of the API-lipid interaction when the formulation was subjected to spray drying, with an indication of the most suitable techniques for this purpose. SLM were prepared with two various lipids (Compritol or stearic acid) and two model APIs: cyclosporine (0.1% and 1% w/w) and spironolactone (0.1% and 0.5% w/w). Physicochemical characterizations of the formulations, before and after spray drying, were performed by differential scanning calorimetry (DSC), atomic force microscopy (AFM), Raman spectroscopy and nuclear magnetic resonance (NMR). The API distribution between the SLM matrix, SLM surface and the aqueous phase was determined, and the release study was performed. It was demonstrated that, in general, the spray drying did not affect the drug release and drug distribution; however, some changes were observed in the SLM with Compritol and when the API concentration was lower. Only in the SLM with stearic acid was a change in the DSC curves noted. Measurements with the AFM technique proved to be a useful method for detecting differences in the surface properties between the placebo and API-loaded SLM, while the Raman spectroscopy did not show such evident differences.

Among the currently available commercial eye drops with cyclosporine A (Cs) there is a lack of long-acting dosage forms and products with a concentration of the drug substance higher than 0.1%, although Cs is widely used in ophthalmology. The aim of the research was to conduct the microscopic and biopharmaceutical evaluation of two formulations, an emulsion (EM) and a self-emulsifying oil (SEO), both with 0.5% of Cs, proposed for use in eye drops, and the comparison of both. SEO eye drops with Cs or any other drug substance are currently not available as marketed products, and the highest concentration of Cs in the ocular emulsion is only 0.1%. The microscopic evaluation of the emulsion and the SEO after emulsification with water was carried out using a high-resolution digital microscopy. The properties of both preparations were compared using the high dynamic range function or optical shadow effect mode. Images in the 3D composition mode were also recorded. The in vivo study of the Cs formulations was performed on male albino rabbits. The eye tolerance of the preparations was assessed using the ocular irritation test, which is a modified Draize test. Placebo carriers (without the drug substance) were also subjected to irritation testing. The concentration of Cs in the tissues (cornea and conjunctiva) and fluids (tear fluid and aqueous humor) of the rabbit eye was determined after multiple instillations of Cs–EM or Cs–SEO. The tested preparations were compared using the digital microscopy technique, which highlights the features of the formulations and eliminates the risk of unnoticeable properties that are difficult to observe in classical optical microscopy. Both tested Cs-loaded formulations are classified as practically non-irritating. There were also no significant differences when testing the placebo carriers. After a topical administration, Cs was widely distributed in all tissues (e.g., in cornea 1.3 ng/mg and 1.0 ng/mg) and fluids of the eye (e.g., in tear fluid 11.6 µg/mL and 4.3 µg/mL), after the administration of Cs–SEO and Cs–EM, respectively. The obtained results allow us to recognize both tested formulations, the emulsion and the self-emulsifying oil with 0.5% Cs content, as carriers safe for ophthalmic use and effective in delivering the drug substance to the structures of the eye.

Polymers in Medicine – a peer-reviewed scientific journal published by Wrocław Medical University, focusing on research on the application of polymers in medicine, pharmacy, and biomaterials.

Cefuroxime sodium (CEF) is a second-generation cephalosporin that remains unstable in an aqueous environment. The answer to this low stability may be self-emulsifying oils, which are isotropic mixtures of oil and surfactants, in which the stability of CEF has already been proven. Self-emulsifying oils are well known for their ability to enhance the solubility and bioavailability of lipophilic drugs. This research presents a preliminary in vivo study of an innovative approach to develop eye drops in the form of a self-emulsifying oil (SEO) containing suspended water-labile antibiotic cefuroxime sodium. Such a concept has never been explored before. Upon contact with tear fluid, the preparation rapidly forms an emulsion, allowing for the rapid dissolution of the antibiotic. The aim of the study was to assess the tolerability of such eye drops. CEF (5% w/w) was suspended in SEO carriers, prepared by dissolving surfactants (Tween 20; 5% w/w) in Miglyol. The in vivo evaluation was conducted on rabbits after two once-a-day applications of the eye drops. The study demonstrated the safety of both the SEO-placebo and the SEO containing suspended CEF. The formulations did not affect the appearance of the cornea and iris. During the observations, only changes in the conjunctiva of the eye were noted, which manifested as conjunctival hyperemia. The result of the Draize test was an average of 3.3 points out of 110 possible points, which classifies the CEF-SEO suspension as minimally irritating.