Acetaminophen particle design using chitosan and a spray-drying technique

Abstract

In this study matrices were prepared from particles of poorly water-soluble drugs such as acetaminophen (Act) to determine the drug release rate from these matrix particles. The matrix particles were prepared by incorporating drugs into chitosan powder (Cht, carrier) using a spray-drying method. The formation of composite particles was confirmed by scanning electron microscopic (SEM) analysis. The matrix particles prepared by spray-drying were spherical with a smooth surface. The crystallinity of acetaminophen in the composite particles was evaluated by powder X-ray diffraction and differential scanning calorimetry (DSC). The degree of crystallinity of acetaminophen in the matrix particles decreased with a reduction in the weight ratio of acetaminophen relative to the carrier. These results indicate that a solid dispersion of acetaminophen in chitosan forms matrix particles. The interaction between acetaminophen and chitosan was also investigated by FT-1R analysis. FT-1R spectroscopy of the acetaminophen solid dispersion suggested that the carbonyl group of acetaminophen and the amino group of chitosan formed a hydrogen bond. There were some differences at pH levels of 1.2 and 6.8 in the release of acetaminophen from the physical mixture compared to the matrix particles. At pH 1.2, the release from the matrix particles (Act:Cht=1:5) was more sustained than from the physical mixtures. The 70% release time, T70, of acetaminophen from the matrix particles (Act:Cht=1:5) increased in pH 1.2 fluid by about 9-fold and in pH 6.8 fluid by about 5-fold compared to crystalline acetaminophen. These results suggest that matrix particles prepared by spray-drying are useful as a sustained release preparation. © 2005 Pharmaceutical Society of Japan.