Preparation and Evaluation of Single and Co-Engineered Combination Inhalation Carrier Formulations for the Treatment of Asthma

Two combination dry powder inhalation formulations were engineered via spray drying and co-spray drying salbutamol base (SB) and beclomethasone dipropionate (BDP). The aerosol performances of the individual drugs, a physical mix and the co-spray-dried particle systems were investigated after blending with conventional lactose carrier, under realistic dose regimes. Furthermore, each system was evaluated in terms of the physicochemical properties and via high-throughput Raman microscopy (to study co-association and deposition patterns after in vitro aerosolisation studies). In general, analysis of the aerosol performance (measured using a next-generation impactor) of the single drug and physical mix formulations suggested that SB and BDP have significantly different stage-deposition profiles. Such observations were further substantiated by scanning electron microscopy, where SB-BDP agglomeration could be observed in the physical mix. Stage deposition from the SB-BDP co-spray-dried powders were different than that for the physical mix, wherein the amount of SB and BDP on each stage was equivalent; suggesting that the two drugs could be targeted and deposited at the same location on the lung epithelia. Raman microscopy of the physical mix and co-spray-dried formulations also confirmed the differences in stage deposition between formulations and co-localised deposition for the co-spray-dried formulation. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:4267-4276, 2012