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

Expert Opin Drug Deliv. 2015 Jan;12(1):1-13. doi: 10.1517/17425247.2014.949235. Epub 2014 Aug 29.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adhesives / chemistry*
  • Animals
  • Antifungal Agents / administration & dosage*
  • Calorimetry, Differential Scanning
  • Candidiasis, Oral / drug therapy*
  • Cellulose / analogs & derivatives
  • Cellulose / chemistry
  • Chemistry, Pharmaceutical
  • Clotrimazole / administration & dosage*
  • Dentures
  • Microbial Sensitivity Tests
  • Nystatin / administration & dosage*
  • Polyethylene Glycols / chemistry
  • X-Ray Diffraction

Substances

  • Adhesives
  • Antifungal Agents
  • Nystatin
  • Polyethylene Glycols
  • Cellulose
  • hydroxypropylcellulose
  • Clotrimazole