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Physicochemical Evaluation of Powder Aggregates in Guiding Formulation Design

Price R, Shur J.

RDD Europe 2013. Volume 1, 2013: 185-196.

Abstract:

An understanding and characterization of the microstructure of carrier-based dry powder inhaler (DPI) blends is key to formulation design. The microstructure of binary, ternary and combination DPI formulations was studied using Raman Chemical Imaging (RCI), in vitro aerosolization performance testing and measurement of surface interfacial properties by the cohesive-adhesive balance (CAB) approach to colloid probe atomic force microscopy (AFM). Post-aerosolization RCI imaging of particles collected from an individual stage of a next generation impactor (NGI) from binary and ternary DPI formulations of budesonide suggested co-deposition of budesonide and lactose fines takes place within the impactor. These data indicate that the microstructure of ternary formulations may consist of drug/lactose agglomerates, suggesting that lactose fines may influence entrainment and deagglomeration efficiency of the active pharmaceutical ingredient. RCI analysis of particles deposited from commercial Seretide® formulations from an individual NGI stage suggested the presence of more free salmeterol xinafoate (SX) particles than free fluticasone propionate (FP), with more FP-lactose forming agglomerates than SX-lactose agglomerates. These differences may be related to the surface interfacial properties of the components of the formulation as suggested by CAB-AFM analysis, which may have resulted in a specific formulation microstructure that aids dispersion of the different drugs using different mechanisms.