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: Differential scanning calorimeter and powder X-ray diffraction 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 fivefold toward the inhibition of cell adherence of Candida 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 min and was maintained for over 10 h. 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.

Keywords:

• bioadhesive film
• hot-melt extrusion
• hydroxypropyl cellulose
• oral candidiasis
• polyethylene oxide

Acknowledgments

The authors would like to thank the Pii Center for Pharmaceutical Technology, the School of Pharmacy, at The University of Mississippi.

Declaration of interest

This project was funded by grant numbers P20GM104931 and R43DE15455-01 from the National Institute of General Medical Sciences (NIGMS) and NIDCR, components of NIH for contributions to this project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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