Effect of Pore Size and Interactions on Paracetamol Aggregation in Porous Polyethylene Glycol Diacrylate Polymers

In this study, we report the results of an all-atom molecular dynamics (MD) based simulation that elucidates the effect of pore size and interactions on the aggregation of paracetamol in polyethylene glycol diacrylate (PEGDA) polymers. Recent experimental studies ( J. Am. Chem. Soc. 2011 , 133 , 3756 - 3759 ) have shown that nucleation rate of paracetamol is highest in one of the PEGDA polymers (PEG200DA) but lack clear understanding of the factors responsible for this anomaly. Our simulation results show that paracetamol aggregation is predominantly governed by the size of PEGDA pores and that the polymer-paracetamol interactions play a secondary role. The probability of formation of paracetamol aggregates, especially of size four, is highest for pore sizes in the range of 14-25 Å, and the drug-drug angle distributions in all the PEGDA polymers that we have studied here have characteristics of both forms I and II of paracetamol crystals. We also demonstrate that the pores in PEGDA polymers can be further engineered by the use of a suitable solvent concentration to achieve pore sizes optimal for improved paracetamol aggregation.