Effect of pharmaceutical formulation on novel nasal drug delivery device

Abstract

Nasal drug delivery has been widely studied for its advantages over conventional drug delivery methods, specifically due to the highly vascularised mucosa of the nasal cavity, which allows for rapid achievement of therapeutic drug levels. A variety of different nasal delivery systems have been studied, with ultrasound being an emerging system that is thought to result in better drug deposition. However, this system has not been studied extensively, and it is not clear how nasal drug formulation interacts with ultrasonic nasal drug delivery. This work investigated the effect of pharmaceutical formulation properties of viscosity, surface tension, and pH on the performance of a commercial ultrasonic nasal drug delivery device and nasal drug absorption. A 33 factorial experimental design, along with a central composite design (CCD) technique was used to carry out a laboratory trial, with the limits set by the ‘extreme’ limits found for the ultrasonic device using a separate set of experiments. 15 formulations of varying amounts of PEG 400, span 80, and HCl were prepared, and measured for viscosity, pH, and surface tension in terms of formulation properties; and droplet size, residual, and delivery rate in terms of ultrasonic device performance. Viscosity and surface tension were found to affect the droplet size, delivery rate, and residual volumes, whilst pH showed no individual significant effects on device performance. The ultrasonic device was found to have a viscosity limit of ~0.003 Pa.s. However, different ultrasonic devices may have different limits, making this an important design consideration. Interactive effects were observed between PEG 400 and HCl, with high concentrations resulting in smaller droplets, which requires consideration to prevent the drug becoming deposited in the upper respiratory tract. In addition to this, controlling the physical formulations properties such as viscosity, surface tension, and pH independently of each other was found to be very difficult due to excipient interactions. Overall, the ultrasonic delivery showed poor repeatability, which would need to be compared with other methods, and given that more viscous formulations are preferred for the nasal route, adjustment of the device viscosity limit is required.