Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: Excipient composites designed for oral inhalation

Abstract

Objectives The aim of this study was to determine if spray-drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation. Methods Trypsin was spray-dried with raffinose from a methanol: n-butyl acetate solvent system (MeOH: BA). The solvent system was then adjusted to include water, and trypsin was co-spray-dried with raffinose, trehalose or hydroxpropyl-β-cyclodextrin. The spray-dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in-vitro deposition of trypsin: excipient nanoporous/ nanoparticulate microparticles (NPMPs) was also assessed. Key findings The inclusion of water in a MeOH: BA solvent system allowed for the successful production of NPMPs of trypsin: excipient by spray-drying. Trypsin formulated as trypsin: excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl-β-cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high-humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin: excipient NPMPs. Conclusions NPMPs of trypsin: excipient systems can be produced by spray-drying by adjustment of the solvent system to allow for adequate solubility of trypsin. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.