Investigation of the stabilising effects of niosomes on the amorphous forms of roxithromycin

Abstract

The first aim of this research study was to determine the effect of the excipients used in the typical niosome preparation on the solid-state nature of three solid-state forms of roxithromycin. The second aim was to ascertain which niosome had the highest concentration of roxithromycin delivered topically to the target-site, the epidermis-dermis (ED) of the skin. To investigate this, roxithromycin, the active pharmaceutical ingredient (API) in this study, was used to prepare the two amorphous forms by the well-known quench cooling of the melt method and recrystallisation of the crystalline raw material (RM) from chloroform. It resulted in the formation of the quench cooled (QC) and chloroform desolvated (CD) amorphous forms. These solid-state forms were characterised in terms of x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) to determine the degree of crystallinity. To explore the effects of the excipients, niosomes were prepared containing five different ratios of cholesterol and Span® 40, with each of the three solid-state forms incorporated in the five formulas resulting in 15 niosome systems. Lipid films (precursors of niosomes) were prepared and the physical stability was investigated, which led to the discovery that the preparation method rendered RM into an amorphous habit, it also showed the amorphous QC and CD remained amorphous. Niosomes were prepared and characterised by means of morphology (microscopy), droplet size and distribution, zeta-potential, pH and drug entrapment efficiency (EE%) to establish if the vesicles had ideal physicochemical properties to be delivered topically to the skin. The characterisation revealed acceptable results and the study progressed towards release studies. Membrane release studies were conducted to evaluate if the API was being released from the vesicle systems and the results obtained showed that the API was released from all the niosomes. Skin diffusion studies were performed to determine if the API was delivered topically and/or transdermally, where it was noted that 4 niosomes were delivered transdermally and therefore into the systemic circulation, while 6 niosomes were found in both the stratum corneum-epidermis and the ED. The aims of this study were reached because the preparation method of the niosomes rendered the crystalline form of the API into an amorphous habit and prevented the amorphous forms from recrystallising. Quantifiable concentrations of the API were delivered to the ED, resulting in successful topical drug delivery. From the three solid-state forms used during this study, niosomes containing the QC amorphous form displayed the best results. It was found the solid-state forms as well the excipients had an influence on the diffusion into and through the skin and it was noticed that specific areas could be targeted using certain excipients