Mucoadhesion and Mucopenetration of Cannabidiol (CBD)-Loaded Mesoporous Carrier Systems for Buccal Drug Delivery
Transmucosal drug delivery represents a promising noninvasive option when drugs are employed which have a low oral bioavailability like CBD. However, this concept can only be successful as long as the formulation provides sufficient buccal retention and mucosal penetration. In this study, mucoadhesive carrier systems were evaluated consisting of CBD-loaded silica (Aeroperl 300) carriers, mucoadhesive polymers (Hypromellose (HPMC), chitosan and carbomer) and propylene glycol as a penetration enhancer. Mucoadhesive effect, drug release and penetration ability were evaluated for each carrier system. The results show that the addition of HPMC and carbomer substantially improve mucoadhesion compared to pure CBD, with an increase of 16-fold and 20-fold, respectively. However, due to their strong swelling, HPMC and carbomer hinder the penetration of CBD and rely on co-administration of propylene glycol as an enhancer to achieve sufficient mucosal absorption. Chitosan, on the other hand, achieves an 8-fold increase in mucoadhesion and enhances the amount of CBD absorbed by three times compared to pure CBD. Thus, chitosan represents a promising polymer to combine both effects. Considering the results, the development of silica-based buccal drug delivery systems is a promising approach for the effective delivery of CBD.
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Article information: Söpper, U.; Hoffmann, A.; Daniels, R. Mucoadhesion and Mucopenetration of Cannabidiol (CBD)-Loaded Mesoporous Carrier Systems for Buccal Drug Delivery. Sci. Pharm. 2021, 89, 35. https://doi.org/10.3390/scipharm89030035
Materials
Synthetically produced Cannabidiol (Canapure > 98% CBD) was kindly provided by Symrise AG (Holzminden, Symrise AG, Holzminden, Germany). Metolose 65SH50 was donated by Shin-Etsu Chemical Co. (Tokyo, Japan), Carbopol 971P NF from Lubrizol Advanced Materials Europe BVBA (Brussels, Belgium), Aeroperl 300 Pharma from Evonik Resource Efficiency GmbH (Hanau, Germany) and Kolliphor PS 80 Ph.Eur. by BASF SE (Ludwigshafen, Germany). Food-grade chitosan was purchased from Harke Pharma GmbH (Mülheim-Ruhr, Germany) and acetonitrile (HPLC grade) from J.T. Baker, Avantor performance Materials B.V. (Deventer, The Netherlands). Hydrochloric acid PF 37%, ethanol (HPLC grade), α–Amylase from Bacillus subtilis (380 U/mg) and mucin from porcine stomach type III were purchased from Sigma-Aldrich Chemie GmbH (Steinheim, Germany). Potassium chloride from VWR International GmbH (Leuven, Belgium) and sodium chloride from Caesar & Loretz GmbH (Hilden, Germany) were Ph.Eur. grade. Refined sunflower oil was purchased from Caesar & Loretz GmbH (Hilden, Germany). Dipotassium hydrogen phosphate trihydrate (Ph.Eur. grade) was purchased from Merck KGaA (Darmstadt, Germany), NEG 50 from Thermo Fisher Scientific Inc. (Waltham, MA, USA) and aluminum foil from FORA GmbH (Radolfzell, Germany). Propylene glycol was donated from Dr. Willmar Schwabe GmbH & Co. KG (Karlsruhe, Germany), Parafilm M from Bemis Company, Inc. (Oshkosh, WI, USA) and Chromafil Xtra H-PTFE-20/25 from Macherey-Nagel GmbH & Co. KG (Düren, Germany). Porcine buccal mucosa was supplied by the Department of Experimental Medicine at the University of Tuebingen and a local butcher. The Department of Pharmaceutical Technology is registered for the use of animal products at the District Office of Tübingen (registration number: DE 08 416 1052 21).
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