Formulation of an emulgel for topical delivery of roxithromycin

Abstract

The aim of this study was to establish whether liposomal or niosomal vesicle systems containing roxithromycin could be developed further into semi-solid formulations (emulgels) for topical delivery of the active pharmaceutical ingredient (API). Resistance against the current first-line treatment of inflammatory lesions has increased, urging the development of a novel acne treatment product. It has been found that the acne causing microorganism located in the epidermis-dermis is susceptible to roxithromycin. Previous studies stated that different solid-state forms of roxithromycin could be included into thin-films, rendering it into an amorphous state irrespective of the initial solid-state. Three solid-state forms of roxithromycin were used for this study, i.e. roxithromycin monohydrate (MH), roxithromycin chloroform solvate (CS) and roxithromycin anhydrate (AH). Fourier-transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) was performed to confirm the properties of these solid-states used; obtained FTIR data correlated with previously reported research. The formulation strategies made use of liposomes or niosomes as drug delivery vesicles. To ensure the suitability of the chosen solid-states and vesicle systems, the vesicles were characterised by means of morphology, droplet size, pH, zeta-potential and drug entrapment efficiency (EE%). Acceptable results were obtained for both liposomal and niosomal dispersions containing the different encapsulated solid-states of roxithromycin. As no topical product containing roxithromycin is currently available on the market, it was decided to establish if the encapsulated API could be formulated into a semi-solid formulation. Every vesicle preparation was included in an emulgel separately. All prepared emulgels had a smooth, gel-like consistency. The liposomal emulgels presented with a light yellow colour, while the niosomal emulgels had a white colour, due to the different excipients used during preparation. The stability of the formulated products was examined over a period of three months, according to the International Conference of Harmonisation (ICH) Tripartite Guideline and the South African Health Products Regulatory Authority (SAHPRA). The stability tests consisted of concentration assay, pH, viscosity, mass loss, zeta-potential, droplet size and physical appearance. The pH and mass variation resulted in satisfactory results over the three months period, whilst the concentration assay, viscosity, zeta-potential and droplet size resulted in unwanted changes. It could thus be concluded that these formulations were not yet suitable for bulk manufacture and improved emulgels ought to be developed.

Membrane release studies were performed on the emulgels, followed by skin diffusion studies and tape stripping. All emulgels resulted in satisfactory API release during the membrane release study. The small amount of API delivery during transdermal diffusion was a favoured outcome, since systemic effects and toxicity would be minimal. All the emulgels permeated the stratum corneum-epidermis. All liposomal emulgels resulted in API delivery to the intended target-site (epidermis-dermis), with the niosomal CS resulting in the best target-site delivery. It was established that quantifiable concentrations of roxithromycin encapsulated in liposomes and niosomes were found at the target-site. It is therefore possible to include encapsulated roxithromycin into an emulgel for topical delivery, but it is necessary to ensure a stable formulation for future use.