A novel production method for inhalable cyclosporine A powders by confined liquid impinging jet precipitation

The aim of this work is to evaluate and optimise aerosol performance of precipitated cyclosporine A (CsA) powders as a model peptide for inhalation drug delivery. Confined liquid impinging jets (CLIJ) was used to precipitate CsA with stabilisers (lecithin and lactose), followed by spray drying to produce dry powders. Minimum concentrations of each stabiliser were determined from a matrix design of nine experimental conditions (i.e. 32 corresponding to 2 additives at 3 concentration levels). Suspensions of CsA particles of 180-700 nm were produced by CLIJ precipitation and powders comprising approximately 1 mu m agglomerates of CsA particles were obtained following spray drying. The internal structure of the agglomerates was not hollow. The aerosol performance of the CLIJ-spray dried powders was initially screened using a dry powder attachment on a laser diffractometer to identify the optimal CLIJ experimental conditions. The optimal aerosol performance was then confirmed using the Aeroliser (R) dry powder inhaler with a multi-stage liquid impinger operating at 60 and 100 L/min. The powder produced from spray drying of the suspension using CLIJ at 1% w/v lactose and 0.025% w/v lecithin showed the best dispersion behaviour and the corresponding aerosol performance shows a fine particle fraction of 54-56%. These results showed the potential of CLIJ precipitation with spray drying in the production of peptides for inhalation. (c) 2008 Elsevier Ltd. All rights reserved.