A quality-by-design and characterization approach was followed to ensure development of self-emulsifying drug delivery systems (SEDDSs) destined for topical delivery of the highly lipophilic clofazimine. Solubility and water-titration experiments identified spontaneous emulsification capacity of different excipient combinations and clofazimine. After identifying self-emulsification regions, check-point formulations were selected within the self-emulsification region by considering characteristics required to achieve optimized topical drug delivery. Check-point formulations, able to withstand phase separation after 24 h at an ambient temperature, were subjected to characterization studies. Experiments involved droplet size evaluation; size distribution; zeta-potential; self-emulsification time and efficacy; viscosity and pH measurement; cloud point assessment; and thermodynamic stability studies. SEDDSs with favorable properties, i.e., topical drug delivery, were subjected to dermal diffusion studies. Successful in vitro topical clofazimine delivery was observed. Olive oil facilitated the highest topical delivery of clofazimine probably due to increased oleic acid levels that enhanced stratum corneum lipid disruption, followed by improved dermal clofazimine delivery. Finally, isothermal microcalometric experiments studied the compatibility of excipients. Potential interactions were depicted between argan oil and clofazimine as well as between Span^®60 and argan-, macadamia- and olive oil, respectively. However, despite some mundane incompatibilities, successful development of topical SEDDSs achieved enhanced topical clofazimine delivery.

Various natural products, including oils, have been utilized as penetration enhancers due to their "safety profiles". These oils contain fatty acids promoting skin permeability through lipid fluidization within the stratum corneum; and might therefore be able to effectively enhance transdermal drug delivery. We investigated possible penetration enhancing properties of selected oils, utilizing flurbiprofen as marker compound in emulgel formulations. The formulations were compared to a liquid paraffin emulgel and a hydrogel to establish any significant penetration enhancing effects. Gas chromatographic analysis of the natural oils was performed at ambient temperature to determine the fatty acid composition in each selected natural oils. Franz cell diffusion studies and tape stripping methods were employed to study delivery of the marker into, and through the skin. The following rank order for the emulgel flux-values was obtained: Hydrogel >>>> olive oil >> liquid paraffin >> coconut oil > grape seed oil >> Avocado oil ≥ Crocodile oil >> Emu oil. Results suggested that oils containing predominantly mono-unsaturated oleic acid, on average increased the flux of the marker to a larger extent than oils containing an almost even mixture of both mono- and poly-unsaturated fatty acids. Oils comprising saturated fatty acids (SFAs) with alkyl chains between C12 and C14, increased the marker flux to a higher extent than oils containing C16-C18 SFAs. Effects observed for branched fatty acids, however, did not vary significantly from effects for unbranched fatty acids with the same carbon chain length. Natural oils possess penetration enhancing effects.

Context: Chitosan does not rank highly regarding its employment as tablet filler due to certain limitations. Undesirable properties that limit its utilization as excipient in solid dosage forms include its hydration propensity that negatively affects tablet stability, strength and disintegration. Objective: The objective of this study was to investigate the physical stability of chitosan powder, mixtures, granules and tablets under accelerated conditions such as elevated temperatures and humidity over different periods of time. Methods: Selected physico-chemical properties of pure chitosan powder, physical mixtures of chitosan with Kollidon® VA64 (BASF, Ludwigshafen, Germany), chitosan granules, as well as tablets were evaluated under conditions of elevated humidity and temperature. Results and discussion: The physical stability of chitosan tablets exhibited sensitivity towards varying exposure conditions. It was furthermore evident that the presence of moisture (sorbed water) had a marked influence on the physical stability of chitosan powder and tablets. It was evident that the presence of Kollidon® VA64 as well as the method of inclusion of this binder influenced the properties of chitosan tablets. The physical stability of chitosan powder deteriorated to a greater extent compared to that of the chitosan tablets, which were subjected to the same conditions. Conclusion: It is recommended that tablets containing chitosan should be stored at a temperature not exceeding 25 °C as well as at a relatively low humidity (<60%) to prevent deterioration of physical properties. Direct compression of chitosan granules which contained 5%w/w Kollidon® VA64 produced the best formulation in terms of physical stability at the different conditions.