Investigation of Physical Changes in Drug-Carrier Interactive Mixtures on Blending

An interactive mixture comprising a model drug, a surfactant and a carrier was created with the aim of investigating the state of drug agglomeration. A light-scatter method was developed to probe changes in agglomeration, by dissolving the excipients, leaving the drug in suspension. Over a period of days post-blending, the level of drug agglomeration appeared to increase. The dissolution rate of the drug was investigated, and this was found to decrease significantly on a similar timescale. This dissolution data was then modelled by considering that dissolution occurred from individually dispersed or aggregated particles, and the model supported an increase in agglomeration. Several hypotheses are proposed for the agglomerate increases, however the role of mechanical processing on fine particle agglomeration remains poorly understood, despite its key role in oral and inhaled drug delivery forms, and the desire to implement a “Quality by Design ” ethos for risk management over the performance of these systems. Background and Objectives We have recently discussed some parallels in the behaviour of agglomerated fine particles in both oral and inhaled formulations (1, 2). In such formulations, the drug is often provided in a finely divided form in order to meet the delivery needs of the medication format. As an inhalation form, the particles are required to disperse into independent aerosol entities that are sufficiently small to avoid impaction on the route into the lungs. As ora