Abstract

The incorporation of drug substances into the matrix of solid lipid microparticles (SLM) is critical to providing effects such as prolonged release, taste masking, and protection of the labile API. Currently, a commonly used method of characterizing multi-compartment lipid systems, such as SLM, is to determine entrapment efficiency (EE) and drug loading (DL) parameters, but this is not sufficient for understanding the localization of API either in the core or on the surface of the microspheres. The main objective of the research was to study the distribution of API in an aqueous dispersion of SLM in order to distinguish between the API incorporated in the lipid matrix and localized in the superficial region (interphase) and to refer the obtained results to the EE and DL parameters. SLM dispersions (10–30% of the lipid) with four model drug substances, i.e., cyclosporine, clotrimazole, diclofenac sodium and hydrocortisone, were prepared and investigated. In the first stage, the experiments were designed to optimize the method of extracting the API fraction localized on the SLM surface by shaking the dispersions with methanol. The fraction dissolved in the aqueous phase was obtained by ultrafiltration of SLM dispersions. Total drug content and the concentration in the separated phases were determined by the HPLC method. The obtained results were compared with the EE and DL parameters. Selected SLM dispersions were tested both before and after thermal sterilization. Short-term shaking of SLM dispersion with methanol does not damage the lipid matrix and allows the API fraction localized on the SLM surface to be extracted, the result of which was the determination of API distribution between lipid matrix, interphase and aqueous phase. It was found that the majority of API represented by EE value was localized on the surface of SLM. Only for cyclosporine was the incorporation of drug molecules in the lipid core very effective (up to 48%), while for other drug substances only 1–21% was found in the lipid core of SLM. A clear influence of the sterilization process on the distribution of API within the microparticles was found. The presented studies showed that the characterization of multi-compartment SLM dispersions solely on the basis of EE and DL values, is insufficient. The proposed new distribution test method enables the localization of API to be demonstrated within the microspheres, with the quantitative characteristics of the drug fraction incorporated in the lipid matrix and the fraction associated with the surface of the lipid matrix. The proposed new method allows the influence of the sterilization process on the changes in the API distribution within the lipospheres to be evaluated. Such characteristics provide new opportunities for the development and use of this dosage form as a carrier providing prolonged release and other aforementioned advantages.

Highlights

  • Solid lipid microparticles (SLM) are drug carriers measured in micrometers, made of lipids with a melting point above human body temperature

  • SLMs, the following conclusions could be presented (Table 4): (i) the tested drug substances can be classified into two categories—for Cyclosporine A (CsA) and KL the incorporation efficiency was very high, and diclofenac sodium (DNa) and HC were incorporated less effectively, but still the level of 24–66% was achieved, (ii) depending on the composition and concentrations significant incorporation efficiency was noted (DL values up to 20%)

  • The presented studies show that the characterization of multi-compartment, lipid dosage form, such as SLM dispersions solely on the basis of EE and drug loading (DL) values, is insufficient and even misleading

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Summary

Introduction

Solid lipid microparticles (SLM) are drug carriers measured in micrometers, made of lipids with a melting point above human body temperature. They can be administered in Pharmaceutics 2022, 14, 335. SLM dispersions can be produced without organic solvents, in a simple process, even on industrial scale, and at relatively low costs [4,12]. They can be sterilized by autoclaving [2,13]

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