Influence of mixing and formulation on agglomeration and functionality of micronised drug powders

This study investigated the influence of mixing conditions and formulation parameters on agglomerate structure and subsequent functionality of micronized drug powders. Powder mixing occurred in a Turbula mixer. Respiratory deposition was measured by the Fine Particle Fraction using a Twin Stage Impinger. Dissolution profiles were determined using the USP paddle method. Particle sizing occurred using laser diffraction with a Malvern Mastersizer S (liquid) and with the Malvern Spraytec (air). The dispersibility of micronized salbutamol sulphate was greater after it had been subjected to conditions of mixing. The presence of non-cohesive excipients such as lactose produced a multi-particulate system consisting of drug-excipient interactive units and drug agglomerates. Particle size distributions were bimodal showing increased concentrations of dispersed particles in media flowing excipient dissolution but a decreased concentration of dispersed particles in air due to strong drug attachment to the excipient. Dissolution functionality was increased but respiratory deposition decreased. The addition of additional micronized excipients to the mixture increased the multi-particulate complexity. The resulting change in agglomerate structure (and subsequent agglomerate strength) increased both the dissolution and respiratory deposition functionality. This study concluded that effective formulation of micronized drugs into solid delivery systems required knowledge of the particulate species produced. The systema??s functionality can be enhanced using appropriate mixing and formulation strategies.