Analytical Techniques for the Assessment of Drug-Lipid Interactions and the Active Substance Distribution in Liquid Dispersions of Solid Lipid Microparticles (SLM) Produced de novo and Reconstituted from Spray-Dried Powders.

Maria Ferreira Monteiro,Eliza Wolska,Małgorzata Sznitowska,Katarzyna Krzemińska

doi:10.3390/pharmaceutics12070664

Maria Ferreira Monteiro, Eliza Wolska + Show 2 more

Open Access

https://doi.org/10.3390/pharmaceutics12070664

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Journal: Pharmaceutics	Publication Date: Jul 15, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: University of Porto, Gdańsk Medical University

Abstract

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.

Highlights

Solid lipid microparticles (SLM) are one of many versatile types of lipid particles with multiple potential applications [1,2,3]
The solid lipid matrix incorporating the API ensures a prolonged release of the API, with the mechanism in vivo depending on the degradation of the matrix lipid [7]
With SLM, one can mask the unpleasant taste of the API or protect it against degradation

Summary

Introduction

Solid lipid microparticles (SLM) are one of many versatile types of lipid particles with multiple potential applications [1,2,3]. SLN, which are the most common subject of research, were introduced in the early 1990s as an alternative drug carrier system to emulsions, liposomes and polymeric microparticles [4]. They were obtained by replacing the oil in an emulsion with a lipid solid at room temperature [5]. SLM were developed on the basis of SLN, but they are bigger particles, in the micrometers size range (usually, 1–100 μm and even up to 1000 μm) [6,7]. Due to the larger particle sizes, in comparison to SLN, SLM can provide higher drug loading and more evident sustained drug release effects. With SLM, one can mask the unpleasant taste of the API or protect it against degradation (i.e., hydrolysis and oxidation)

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