Engineered lactose carrier partciles: does latered microstructure give improved performance?

The primary function of a carrier particle in a Dry Powder Inhaler (DPI) is to improve the powder flow of otherwise cohesive micronized drug particles. The carrier aids flow during manufacture and operation: i.e. including mixing, transport, metering and dispersion. Traditionally, such carriers are generally between about 50 and 150A?m in size, to provide the required powder flow, and typically take the form of a Tomahawk crystalline shape. However, these conventional carriers have significant limitations. They can suffer poor flow once mixed with more than 10 to 20 w/w micronized material, whereby bulk powder cohesion due to the carrying surface becoming saturated, and the presence of loose fines becomes too great. Previously, some efforts have been made to address this dose restriction, either by developing much smaller, surface treated carriers , or by employing much larger carriers comprising an agglomerated structure. This latter approach has relied on modified rugosity of the carriers, to absorb the fine components, resulting in a structured pellet-like formulation. We report here a novel direct approach, developed to pilot-scale, to engineer specialist lactoses with very high rugosity and reduced density, via a single crystallization step. The size and morphology of the crystals can be varied by controlling the crystallization conditions such as feed purity, temperature, cooling rate and period of crystal growth. In one aspect, the crystallization can be controlled to provide a complex open structure which appears suited for enhanced payload carrying. The current study examines the potential of his alternative approach to engineer high-performance carrier particles for use in DPIs.