Amorphous Spray Dried Microparticles for Nasal Delivery: Tackling Solubility Challenges while Targeting Systemic Nasal Absorption
Patricia Henriques1,2, Cláudia Costa1, António Serôdio1, Ana Fortuna2,3, Slavomíra Doktorovová1
1 Hovione FarmaCiência SA, Lumiar, 1649-038, Portugal
2 Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
3 Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, 3000-548 Coimbra, Portugal
Summary
Dry powder formulations for nasal drug delivery can be manufactured by spray drying, a technology that allows particle size control and the generation of amorphous solid dispersions for drug solubility enhancement. Targeting the turbinate area of the nasal cavity is relevant for drugs intended for systemic delivery that benefit from the fast absorption and quick onset of action provided by the vascularised nasal mucosa. Despite the current knowledge on spray dried powders for nasal delivery, the impact of different polymers on drug release performance is still not clear, as well as the deposition profile of this formulation strategy. Herein, amorphous spray dried microparticles were evaluated regarding their supersaturation behaviour and drug release performance, comparing with the corresponding physical blends. The lead formulation was additionally assessed regarding nasal deposition profile using the Alberta Idealized Nasal Inlet, while evaluating the impact of the angle of actuation from horizontal plane and inhalation flow rate. The results showed enhanced drug release performance for the amorphous formulations, where the polymer that sustained supersaturation for a longer period of time resulted in higher drug release. Nasal deposition studies with an angle of actuation of 45º and inhalation flow rate of 15 L/min showed high mass balance of 97% and high turbinate deposition of 55%. Overall, the results support that spray drying is an adequate strategy to manufacture microparticles with high turbinate deposition. Moreover, the combined performance evaluation strategy using dissolution, drug release and nasal deposition methodologies was adequate to characterise and select lead formulation candidates.