Solid dispersion of acetaminophen and poly(ethylene oxide) prepared by hot-melt mixing

Abstract

In this study, a model drug, acetaminophen (APAP), was melt mixed with poly(ethylene oxide) (PEO) using a Brabender mixer. APAP was found to recrystallize upon cooling to room temperature for all the drug loadings investigated. Higher drug loading leads to faster recrystallization rate. However, the morphology of the recrystallized drug crystals is identical in samples with different drug loadings and does not change with the storage time. To adjust the drug's dissolution rate, nanoclay Cloisite 15A and 30B were added into the binary mixture. The presence of either of the nanoclay dramatically accelerates the drug's recrystallization rate and slows down the drug's releasing rate. The drop of the releasing rate is mainly due to the decrease of wettability, as supported by the contact angle data. Data analysis of the dissolution results suggests that the addition of nanoclays changes the drug's release mechanism from erosion dominant to diffusion dominant. This study suggests that nanoclays may be utilized to tailor the drug's releasing rate and to improve the dosage form's stability by dramatically shortening the lengthy recrystallization process.