Fabrication of Smart Intraoral Drug Delivery Systems

Abstract

The intraoral delivery of drugs has emerged as a promising alternative to the oral administration, offering enhanced bioavailability and improved patient compliance. Despite the existence of traditional intraoral dosage forms, such as disintegrated tablets, the lack of control over drug release and enclosing large amounts of excipients compromised their wider application. Smart drug delivery systems have arisen to address these limitations. This doctoral thesis aimed at developing smart intraoral drug delivery systems with superior precision and enhanced customisation over drug release, leveraging emerging fabrication technologies. Initially, coaxial electrospinning was used to fabricate intraoral fast dissolving films comprising a fixed dose combination. Disintegration analysis revealed that these films were able to disintegrate within 2 seconds, significantly surpassing their solvent-cast counterparts. Subsequently, three-dimensional (3D) printing was utilized to fabricate intraoral electro-responsive films for electrically-charged drugs, showcasing programmable, voltage-controlled drug release. The results indicate a statistically significant difference in the release profiles of the drugs between samples subjected to electrical stimulation using the optimized voltages compared to those without voltage application. Building on the developments from Chapter three, an innovative approach was developed to expand the utility electro-responsive to work with neutrally-charged drugs, marking the first exploration in this area. This research brought together a number of technologies to achieve this novel aim. Briefly, PLGA microparticles containing a neutrally-charged drug were fabricated using electrospray, which were subsequently-loaded onto the electro-responsive film. In vitro analysis confirmed a statistically significant difference in release profile between applying a passive volt (i.e., 0.0 V) and an expulsive volt (-1.0 V), where the latter resulted in a threefold increase in drug release. In summary, this thesis introduces pioneering systems contributing to the advancement of intraoral drug delivery and highlights the transformative potential of emerging fabrication technologies in the development of such systems.