Theophylline particle design using chitosan by the spray drying

Solid dispersions of theophylline with chitosan as a carrier were prepared using a spray-drying method. Chitosan dissolved in an acid solution forms a gel, but it does not dissolve in an alkaline solution. Therefore, drugs which form composite particles with chitosan would gradually be released in an acid solution, and are expected to have considerably sustained release in an alkaline solution. In this study, we aimed to apply this ability to sustained release pharmaceutics. In this study, we used theophylline as a model drug and chitosan as a carrier. Mixtures of chitosan and the drug in prescribed ratios were dissolved in an acid solution. The physicochemical properties of the solid dispersions obtained were investigated by powder X-ray diffraction, differential scanning calorimetry, and dissolution rate analyses, with a view to clarify the effect of crystallinity on the dissolution rate. Furthermore, the interaction between the drug and the carrier was investigated by FT-IR analysis. The powder X-ray diffraction intensity of the drug in the spray-dried samples decreased with an increase in chitosan contents, which also caused changes from crystalline to amorphous forms. These results indicated that the system formed a solid dispersion. The dissolution profiles of the drug from the physical mixtures and-solid dispersions were almost the same at pH 1.2. However, at pH 6.8, the release from the solid dispersions was sustained more than that from the physical mixtures. The FT-IR spectroscopy for the theophylline solid dispersions suggested that the carbonyl group of theophylline and the amino group of chitosan formed a hydrogen bond. Mass median aerodynamic diameter (MMAD) was measured by using a cascade impactor to evaluate the possibility of solid dispersions as dry powder inhalations. The MMAD of the spray-dried theophylline-chitosan systems were 4.5-5.0 mum. The results suggested that the spray-drying method is usefull to produce dry powders for inhalation. (C) 2003 Elsevier B.V. All rights reserved.