Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods.

Khalid Doudin,Enas Al-Ani,David Hill

doi:10.3390/ph14060493

Abstract

Oropharyngeal candidiasis (OPC) is a mucosal infection caused by Candida spp., and it is common among the immunocompromised. This condition is mainly treated using oral antifungals. Chlorhexidine (CHD) is a fungicidal and is available as a mouth wash and oral gel. It is used as an adjuvant in the treatment of OPC due to the low residence time of the current formulations. In this study, its activity was tested against C. albicans biofilm and biocompatibility with the HEK293 human cell line. Then, it was formulated as mucoadhesive hydrogel buccal tablets to extend its activity. Different ratios of hydroxypropyl methylcellulose (HPMC), poloxamer 407 (P407), and three different types of polyols were used to prepare the tablets, which were then investigated for their physicochemical properties, ex vivo mucoadhesion, drug release profiles, and the kinetics of drug release. The release was performed using Apparatus I and a controlled flow rate (CFR) method. The results show that CHD is biocompatible and effective against Candida biofilm at a concentration of 20 µg/mL. No drug excipient interaction was observed through differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The increase in P407 and polyol ratios showed a decrease in the swelling index and an increase in CHD in vitro release. The release of CHD from the selected formulations was 86–92%. The results suggest that chlorhexidine tablets are a possible candidate for the treatment of oropharyngeal candidiasis.

Highlights

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Albicans biofilms to be incorporated in the tablets
The following materials were purchased from Sigma Aldrich, UK: sabauroud dextrose agar (SDA), Muller Hinton broth (MHB), chlorhexidine diacetate salt hydrate (CHD), RPMI-1640 dry powder (RPMI), 3-(n-Morpholino) propane sulfonic acid (MOPS), acetone

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Oropharyngeal candidiasis (OPC) is a common opportunistic infection in immunocompromised patients, caused by Candida spp. and, most commonly, C. albicans. The annual estimated number of OPC cases is 10 million globally. The treatment of OPC is hampered by the limited number of antifungal drugs available, drug resistance, drug–drug interaction, and adverse effects. Uncontrolled OPC could result in systemic candidiasis, which has a mortality rate of 30–50% [1,2]

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