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

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.

3D Printed Buccal Films for Prolonged-Release of Propranolol Hydrochloride: Development, Characterization and Bioavailability Prediction

“…In this study, the best mathematical model for all formulations was first-order kinetic, which means that the release rate shows dependence on PRH concentration, and it is proportional to the drug remaining in the matrix [36,70]. The Korsmeyer-Peppas model also resulted in a good fit, which is why we calculated the release exponent (n value) to understand the PRH release mechanism from buccal films better [37]. Formulation F2 has an n value lower than 0.5, suggesting that the PRH release followed the Fickian diffusion mechanism.…”

“…The release kinetics of the PRH from the buccal films were analyzed using the DD-Solver software (Microsoft Excel add-in program) developed by Zhang et al [34]. The cumulative drug release data were fitted with different mathematical models, including zero-order, first-order, Higuchi, and Korsmeyer-Peppas models [35][36][37]. The highest values of the coefficient R 2 and the model selection criterion (MSC) were utilized to determine the best fitting model [37].…”

“…The cumulative drug release data were fitted with different mathematical models, including zero-order, first-order, Higuchi, and Korsmeyer-Peppas models [35][36][37]. The highest values of the coefficient R 2 and the model selection criterion (MSC) were utilized to determine the best fitting model [37].…”

“…Formulation F2 has an n value lower than 0.5, suggesting that the PRH release followed the Fickian diffusion mechanism. Formulations F4 and F6 have an n value between 0.5 and 1, meaning that the PRH release mechanism is both swelling and diffusion and follows anomalous or non-Fickian transfer [37,38,71]. In formulation F4, besides the formation of hydrogen bonds between molecules of the same polymer, there are also established hydrogen bonds between two different macromolecules (hydroxyl groups of the GA and carbonyl groups of PVP; amine groups of the GA and carbonyl groups of PVP).…”

“…Formulation F2 has an n value lower than 0.5, suggesting that the PRH release followed the Fickian diffusion mechanism. Formulations F4 and F6 have an n value between 0.5 and 1, meaning that the PRH release mechanism is both swelling and diffusion and follows anomalous or non-Fickian transfer [37,38,71].…”