Solid cellulose nanofiber based foams – Towards facile design of sustained drug delivery systems

Abstract

Control of drug action through formulation is a vital and very challenging topic within pharmaceutical sciences. Cellulose nanofibers (CNF) are an excipient candidate in pharmaceutical formulations that could be used to easily optimize drug delivery rates. CNF has interesting physico-chemical properties that, when combined with surfactants, can be used to create very stable air bubbles and dry foams. Utilizing this inherent property, it is possible to modify the release kinetics of the model drug riboflavin in a facile way. Wet foams were prepared using cationic CNF and a pharmaceutically acceptable surfactant (lauric acid sodium salt). The drug was suspended in the wet-stable foams followed by a drying step to obtain dry foams. Flexible cellular solid materials of different thicknesses, shapes and drug loadings (up to 50wt%) could successfully be prepared. The drug was released from the solid foams in a diffusion-controlled, sustained manner due to the presence of intact air bubbles which imparted a tortuous diffusion path. The diffusion coefficient was assessed using Franz cells and shown to be more than one order of magnitude smaller for the cellular solids compared to the bubble-free films in the wet state. By changing the dimensions of dry foams while keeping drug load and total weight constant, the drug release kinetics could be modified, e.g. a rectangular box-shaped foam of 8mm thickness released only 59% of the drug after 24h whereas a thinner foam sample (0.6mm) released 78% of its drug content within 8h. In comparison, the drug release from films (0.009mm, with the same total mass and an outer surface area comparable to the thinner foam) was much faster, amounting to 72% of the drug within 1h. The entrapped air bubbles in the foam also induced positive buoyancy, which is interesting from the perspective of gastroretentive drug-delivery.