Development of an antifungal denture adhesive film for oral candidiasis utilizing hot melt extrusion technology

Abstract

Objectives The overall goal of this research was to produce a stable hot-melt extruded “Antifungal Denture Adhesive film” (ADA) system for the treatment of oral candidiasis. Methods The ADA systems with hydroxypropyl cellulose (HPC) and/or polyethylene oxide (PEO) containing clotrimazole (10%) or nystatin (10%) were extruded utilizing a lab scale twin-screw hot-melt extruder. Rolls of the antifungal-containing films were collected and subsequently die-cut into shapes adapted for a maxillary (upper) and mandibular (lower) denture. Results DSC and PXRD results indicated that the crystallinity of both APIs was changed to amorphous phase after hot-melt extrusion. The ADA system, containing blends of HPC and PEO, enhanced the effectiveness of the antimicrobials a maximum of 5-fold toward the inhibition of cell adherence of C. albicans to mammalian cells/Vero cells. Remarkably, a combination of the two polymers without drug also demonstrated a 38% decrease in cell adhesion to the fungi due to the viscosity and the flexibility of the polymers. Drug-release profiles indicated that both drug concentrations were above the minimum inhibitory concentration (MIC) for C. albicans within 10 minutes and was maintained for over 10 hours. In addition, based on the IC50 and MIC values, it was observed that the antifungal activities of both drugs were increased significantly in the ADA systems. Conclusions Based on these findings, the ADA system may be used for primary, prophylaxis or adjunct treatment of oral or pharyngeal candidiasis via controlled-release of the antifungal agent from the polymer matrix.

Orodispersible films: Towards drug delivery in special populations

“…Hot melt extrusion (HME) offers the advantage of a solvent-free process for ODF manufacturing (Palem et al, 2016(Palem et al, , 2013Park et al, 2015;Repka et al, 2003). Yet, poor availability of suitable polymers and high temperatures may pose stability issues to the active (Hoffmann et al, 2011).…”

Fabrication of mucoadhesive chitosan coated polyvinylpyrrolidone/cyclodextrin/clotrimazole sandwich patches for oral candidiasis

“…Among the various Candida species, Candida albicans is still considered the most important fungal pathogen responsible for this disease (Budtz-Jorgensen, 1990;Wady et al, 2012). Many factors, including immunodeficiency and poor oral hygiene, can predispose a patient to this fungal infection (Park et al, 2015). The antifungal drugs including polyenes and azole antimycotics can be used either topically or systemically (Pallasch, 2002;Tonglairoum, Ngawhirunpat, Rojanarata, Kaomongkolgit, & Opanasopit, 2015).…”

Effects of absorbent materials on a self-emulsifying drug delivery system for a poorly water soluble drug

“…(Draheim et al 2015;Kanzarkar et al 2015;Park et al 2015;Tang et al 2008;Weerapol et al 2015). Among these techniques, the adsorption process is the simplest and the most commonly used method of transforming formulations from liquid to solid, performed by simply combining them with solid absorbable carriers in a blender.…”