Topical delivery of roxithromycin solid-state forms entrapped in vesicles.

Recently, considerable interest developed in using newer/improved antibiotics for the treatment of Acne vulgaris. During this study, different roxithromycin solid-state forms (i.e. crystalline and amorphous) were encapsulated into vesicle systems (niosomes, proniosomes, ufosomes and pro-ufosomes) for dermis targeted delivery. Characterization of the vesicles was done with transmission electron microscopy, light microscopy, droplet size, droplet size distribution, pH, zeta-potential and entrapment efficiency percentage. Finally, comparative release and topical diffusion studies were performed, to evaluate if targeted topical delivery was obtained and if the roxithromycin solid-state amorphous forms resulted in improved topical delivery. Vesicle systems containing different roxithromycin (2%) solid-state forms were successfully prepared and characterized. The vesicles showed optimal properties for topical delivery. All carrier systems had topical delivery to the epidermis-dermis, whilst no roxithromycin was found in the receptor compartment or stratum corneum-epidermis. The niosomes were the leading formulation and the two amorphous forms had better topical delivery than the crystalline form. Successful targeted delivery of roxithromycin was obtained in the dermis, where the activity against Propionibacterium acnes is needed. The amorphous forms seemed to have held their solid-state form during formulation and in the vesicles, showing improved topical delivery in comparison to the crystalline form.

Different amorphous solid-state forms of roxithromycin: A thermodynamic and morphological study.

The striking impact that different preparation methods have on the characteristics of amorphous solid-state forms has attracted considerable attention during the last two decades. The pursuit of more extensive knowledge regarding polyamorphism therefore continues. The aim of this study was firstly, to investigate the influence of different preparation techniques to obtain amorphous solid-state forms for the same active pharmaceutical ingredient, namely roxithromycin. The preparation techniques also report on a method utilizing hot air, which although it is based on a melt intermediary step, is considered a novel preparation method. Secondly, to conduct an in-depth investigation into any physico-chemical differences between the resulting amorphous forms and thirdly, to bring our findings into context with that of previous work done, whilst simultaneously discussing a well-defined interpretation for the term polyamorphism and propose a discernment between true polyamorphism and pseudo-polyamorphism/atypical-polyamorphism. The preparation techniques included melt, solution, and a combination of solution-mechanical disruption as intermediary steps. The resulting amorphous forms were investigated using differential scanning calorimetry, X-ray powder diffraction, hot-stage microscopy, scanning electron microscopy, and vapor sorption. Clear and significant thermodynamic differences were determined between the four amorphous forms. It was also deduced from this study that different preparation techniques have a mentionable impact on the morphological properties of the resulting amorphous roxithromycin powders. Thermodynamic properties as well as the physical characteristics of the amorphous forms greatly governed other physico-chemical properties i.e. solubility and dissolution.