Buccal films are recognized as easily applicable, microbiologically stable drug dosage forms with good retentivity at the mucosa intended for the therapy of oromucosal conditions, especially infectious diseases. Multilayer films composed of layers of oppositely charged polymers separated by ionically interacting polymeric chains creating polyelectrolyte complexes represent very interesting and relatively poorly explored area. We aimed to develop the antifungal multilayer systems composed of cationic chitosan and anionic pectin as potential platforms for controlled delivery of clotrimazole. The systems were pharmaceutically characterized with regard to inter alia their release kinetics under different pH conditions, physicomechanical, or mucoadhesion properties with using an animal model of the buccal mucosa. The antifungal activity against selected Candida sp. and potential cytotoxicity with regard to human gingival fibroblasts were also evaluated. Interactions between polyions were characterized with Fourier transform infrared spectroscopy. Different clotrimazole distribution in the films layers highly affected their in vitro dissolution profile. The designed films were recognized as intelligent pH-responsive systems with strong antifungal effect and satisfactory safety profile. As addition of chitosan resulted in the improved antifungal behavior of the drug, the potential utilization of the films in resistant cases of oral candidiasis might be worth of further exploration.
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.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.