Development of mucoadhesive carrier systems for flavoring agents and cannabidiol

Abstract

The buccal mucosa represents an attractive site to realize both local and systemic effects. It is easily accessible and transbuccal drug delivery offers the opportunity to increase bioavailability of drugs by avoiding first-pass metabolism and intestinal drug degradation. But despite numerous advantages, it remains challenging to exploit the full potential of the buccal region. The main limitations derive from the barrier properties of the mucosa and the removal mechanism by the salivary flow in the oral cavity. Therefore, an effective buccal drug delivery formulation requires adequate adhesion and, for systemic effects, additionally sufficient mucosal penetration. Three objectives were investigated in this work. The first one was to develop carrier systems based on a flavor-loaded porous silica and a mucoadhesive polymer. In addition to stabilizing the volatile flavor, the carrier system was intended to use mucoadhesion to prolong the effects of flavoring agents in the oral cavity. The second part of the work investigated whether the formulation approach can also be transferred to drug-loaded carrier systems. For this purpose, CBD was selected as a model API given its strong need for an alternative administration route based on its poor oral bioavailability. It was hypothesized that the mucoadhesive delivery systems would result in an extended and intimate contact with the mucosa, and thereby favor the absorption of CBD. Finally, regarding taste compliance, it was of interest to clarify whether mucoadhesive carrier systems with a combination of flavoring agent and CBD are feasible. The results demonstrated that functionalization of flavor-loaded silica carrier systems with mucoadhesive polymers is a promising formulation approach for prolonged availability of flavors in the oral cavity. Stability studies confirmed that the volatile flavors can be stabilized by the formulations in the carrier systems for months. DSC studies revealed that the decisive factor for stability was the physical state of the flavor in the carrier system. The flavor content was stable, when the load limit of the silica was not exceeded, and the flavoring agent was completely deposited in an amorphous state to the silica carrier. The improved adhesion of the flavoring agents to the oral mucosa was evaluated by ex-vivo mucoadhesion studies. Among the tested formulations, the combination of Aeroperl 300 as the carrier material, sunflower oil as a coating medium and carbomer as the mucoadhesive polymer proved to be superior in terms of a strong and long-lasting mucoadhesive effect than other combinations. In summary, a large surface area and large pore volume of the silica proved to be desirable for the loading and coating process. The magnitude of the mucoadhesive effect was determined by the polymer concentration, the ability of the polymer to form bonds with the mucus layer, its particle size and the coating medium applied.