Manipulation of beclomethasone-hydrofluoroalkane interactions using biocompatible macromolecules.

The aim of this work was to physically stabilise beclomethasone dipropionate (BDP) microparticles within a hydrofluoroalkane (HFA) propellant using biocompatible polymers in order to allow the efficient delivery of the steroid to the airways from a pressurised metered dose inhaler (pMDI). BDP microparticles were coated with a number of different "amphiphilic" macromolecular excipients by spray-drying an aqueous BDP suspension in which the excipients were dissolved. The physical stability of the coated BDP microparticles was assessed both indirectly using a twin-stage impinger (TSI) and directly using "in-situ" laser diffraction particle size analysis in a range of nonpolar solvents. The solubility of the formulation excipients within a number of the nonpolar vehicles was determined using an internally manufactured filtration rig and the influence of zeta potential within the microparticle suspensions measured in a series surrogate nonpolar systems. The size of the pure BDP microparticles increased significantly (p < 0.05, ANOVA) from 3.13 +/- 0.15 microm to 9.86 +/- 0.50 microm upon suspension within a nonpolar HFA solvent. However, the addition of poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) to the BDP microparticles dramatically reduce this aggregation leading to the production of physically stable suspensions with excellent aerosolisation properties (Stage 2 deposition >40% in the twin-stage impinger). It is postulated that the enhanced physical stability observed when PVA and PVP are coated onto BDP microparticles is partially as a result of steric stabilisation in HFA solvents. However, the large zeta potential associated with the nonpolar microparticle suspensions suggest that charge stabilisation may also influence the physical stability within these systems. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association