Impact of salts on spray dried inhaled dual site targeting mannitol powder for radiolabelling procedure
Han Cong Seow1,2, Michael Y.T. Chow1, Zhu Zilan1, Mridul Majumder3 & Jenny K.W. Lam1,2
1Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
2Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR
3M2M Pharmaceuticals Ltd., Unit 125 (Gr Fl) Wharfedale Road Winnersh Triangle RG41 5RB, Berkshire, UK
Summary
Dual site targeting approach is an innovative aerosol drug delivery strategy to target both upper and lower respiratory tracts by intranasal administration. The idea is to produce powders of distinctly large (>10 μm) and small (<5 μm) sizes for nasal and lung deposition, respectively, and by manipulating the powder mixing ratio, their deposition profile can be controlled. To validate this concept, we aim to produce radiolabelled powders for a clinical deposition study. During radiolabelling, substantial amount of salts are added to stabilise the radioactivity. As high salt content may affect the spray drying process and the physicochemical properties of the powder, our main objective was to investigate the effect of salts on the powder produced by co-spray drying mannitol with salts required for radiolabelling. It was found that the additional salt content decreased the production yield, increased the residual moisture and particle size of the powders. By blending the powders of different size, the particle size distribution varied linearly with the mixing ratio. This linear trend could still be observed in the powders containing 10% w/v salt. Overall, a dual site targeting powder formulation of mannitol for radiolabelling was developed for subsequent use in clinical deposition study to validate the dual targeting formulation approach as a promising strategy for delivering therapeutic agents to the nasal cavity and the lungs.