Aerosol loaded toroidal vortices for enhanced ocular drug delivery
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Over that last few decades there has been an increase in the creation of new medicinal agents to treat various ophthalmic diseases, from small molecule drugs to highly targeted biologics. While these advances in drug discovery have enabled a new wave of therapies, many problems regarding their accurate, reproducible and safe administration still remain. The standard vehicle for topical ocular drug delivery is the eye drop, and despite its popularity, there are some significant limitations to their use. It is estimated that in many cases less than 5% of the active reaches the target tissues. While the remainder of the dose is either spilled out onto surrounding tissue or it is rapidly drained through the lacrimal ducts where it can be absorbed into the systemic circulation. Current drug delivery technologies have focused on improving bioavailability and patient compliance, and it is expected that further improvements can be made in these areas by incorporating the use of precision drug loaded aerosol vortices. Within the framework of this dissertation, two main aspects of a novel ophthalmic aerosol drug delivery device were investigated; the mechanical features that dictate the dose delivery, and the formulation aspects that control the characteristics of the aerosols that are being delivered. In early studies, investigations into the mechanism of the dose deposition were explored in order to gain knowledge into predicting the performance and to tune the delivery of a wide range of therapeutic concentrations. In later studies, after the device and dosing characteristics where established, studies were conducted on different formulation strategies in order to incorporate active pharmaceutical ingredients that would otherwise have unfavorable physicochemical characteristics for incorporation into an aqueous based system. These studies included the use of solubilizing agents and their effect on the characteristics of the aerosol generated from the device, as well as a novel particle engineering technology that could be utilized to incorporate the use of nanoparticles or colloidal particulates into the device or for other uses. The use of these formulation techniques thereby increases scope of therapeutic agents that can be incorporated for use in the device, further improving its therapeutic potential.
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