Material characterisation and parameter effects on bulk solid dissolution rate of paracetamol in a stirred tank vessel using an in situ UV-ATR probe

Abstract

The progress from batch to continuous manufacture of pharmaceuticals has highlighted the requirement for dosing solid feed material directly, efficiently and accurately into continuous flow systems. Solids are currently dissolved in batch vessels before feeding into a flow system. This study focuses on gaining scientific understanding on rate kinetics of solid dissolution and parameters affecting solid dosing in current batch systems as a starting point; the knowledge gained will inform future continuous solid dosing work. Paracetamol was the model compound and the mixtures of water/ IPA the solvent systems. An in situ UV spectrometer was used to quantify the concentration of solute in solution during dissolution. In this paper, we present the dissolution kinetics results from a parametric study of effects of temperature, solvents, mixing and particle sizes on dissolution characteristics in a stirred tank vessel. The dissolution profiles from our system are similar to that of published work, with the fastest kinetics for the micronised particles, albeit problematic when dosing as a single shot. Dissolution rate is increased with increasing temperature, solvent content (solubility), mixing intensity and decreasing particle size