Buccal delivery of small molecules - Impact of levulinic acid, oleic acid, sodium dodecyl sulfate and hypotonicity on ex vivo permeability and spatial distribution in mucosa

Studies of drug permeability rate and localization in buccal mucosa are essential to gain new knowledge of means such as chemical enhancers or osmolality to enhance buccal drug transport in the development of new buccal drug products. The transport of caffeine, diazepam and mannitol across porcine buccal mucosa was studied in modified Ussing chambers with a hypotonic donor solution, in the presence of levulinic acid (LA), oleic acid (OA), propylene glycol (PG) as well as sodium dodecyl sulfate (SDS). Subsequently, matrix-assisted laser desorption ionization - mass spectrometry imaging (MALDI-MSI) was applied to image the spatial distribution of caffeine, mannitol and SDS in cross-sections of porcine buccal mucosa. The results revealed that none of the permeation enhancing strategies improved the permeability of caffeine or diazepam, despite impact on the tissue integrity by OA and SDS, as seen by an increased permeability of mannitol. Further studies are needed with OA since PG solvent may have concealed the possible impact of OA. SDS decreased the permeability of caffeine and diazepam, a decrease which can be explained by micellar lipid extraction and encapsulation in micelles. MALDI-MSI showed that SDS permeated into approximately one-third of the epithelium, and it therefore appears that the main permeability barrier for mannitol is located in the outer epithelium. MALDI-MSI was shown to be a useful method for imaging spatial distribution of drugs and permeations enhancers in buccal mucosa.