Irès van der Zwaan1 Pegah Nabavi2 Adam Feiler2,3
1Department of Pharmaceutical Biosciences and Swedeliver, Uppsala University, Husargatan 3, Uppsala, 75237, Sweden
2Nanologica, Forskargatan 20G, SE-151 36 Södertälje, Sweden
3KTH, Royal Institute Technology, Department of Chemistry, Drottning Kristinas väg, 51SE-100 44 Stockholm
Summary
A novel pulmonary drug delivery system has been developed comprising of nanoporous, micron-sized, amorphous silica particles to encapsulate drug substances. The particle size of these nanoporous particles (NPPs) can be tightly controlled, as can the diameter of the pores. The particles enhance the solubility of poorly soluble compounds and may also offer the potential to control the release rate of drug to the lungs. The objective of this study was to investigate the effect of particle size and pore size on drug release profiles of loaded NPPs which were aerosolized from a dry powder inhaler.
To study the effect of particle size, NPPs ranging from 2.5 µm to 5.0 µm, with identical pore sizes, were loaded with budesonide. To explore the effect of pore size, NPPs of the same size (2.2 µm), but different pore diameters (2 nm and 7 nm) were loaded with a highly insoluble novel drug candidate (CMPD-X).
A modified Andersen cascade impactor (mACI) was used to characterise the deposited particle fraction. Budesonide dissolution from the particles was studied in simulated lung fluid (SLF; Gamble’s solution). The dissolution rate of budesonide was greater after being loaded in NPPs compared to budesonide particles taken from a Pulmicort® Turbuhaler®. Reducing particle size of NPPs from 5.0 µm to 2.5 µm increased the rate of dissolution of budesonide. Looking at the effect of pore size on release rate of CMPD-X, the data showed that reducing the pore diameter from 7 nm to 2 nm decreased the release rate of the drug. It is notable that regardless of the pore size, encapsulating CMPD-X into NPPs significantly increased the amount of drug released into solution. Together these results strongly indicate that the ability to control both particle size and the pore diameter of the NPPs could offer a significant formulation advantage for some drugs in development.
Key Message
Both the particle size and the pore diameter of nanoporous amorphous silica particles can be controlled and utilised to influence the rate at which encapsulated drugs are released into solution. This may offer a significant formulation advantage for some drugs intended for pulmonary delivery.