An investigation into the production of paracetamol solid dispersions in PEG 4000 using hot stage differential interference contrast microscopy

Abstract

The melting and crystallisation behaviour of paracetamol dispersions in polyethylene glycol (PEG) 4000 has been studied using differential interference contrast microscopy fitted with a hot stage. The effects of thermally cycling physical mixes of the two components have been studied with particular reference to the effects of the presence of molten PEG 4000 on the melting behaviour of the model drug. The effects of the drug particle size, the maximum temperature of heating and the holding time at the maximum temperature on the solid dispersion structure have been investigated, with profound changes in structure being observed depending on the manufacturing protocol used. In particular, higher maximum temperatures and holding times with lower drug particle sizes promoted greater dissolution of the drug into the molten PEG. In the majority of systems observed, the remaining paracetamol particles simply persisted as the system was cooled. However, for certain systems, involving high drug loadings and extended holding times and temperatures in the liquid state, the drug recrystallised over a 24-h period to form a fine dispersion within the carrier. The study has therefore demonstrated the usefulness of hot stage microscopy as a method of directly observing the processes involved during the manufacture of solid dispersions and has also indicated that changing the manufacturing protocol may have a profound effect on the structure of the dispersion.