Effect of method of preparation and process variables on controlled release of insoluble drug from chitosan microspheres

An inexpensive and simple method was adopted for the preparation of chitosan microspheres, crosslinked with glutaraldehyde (GA), for the controlled release of an insoluble drug-ibuprofen, which is a commonly used NSAID (non-steroidal anti-inflammatory drug). The chitosan microspheres were prepared by different methods and varying the process conditions such as rate of stirring, concentration of crosslinking agent, and drug:polymer ratio in order to optimize these process variables on microsphere size, size distribution, degree of swelling, drug entrapment efficiency, and release rates. The absence of any chemical interaction between drug, polymer, and the crosslinking agent was confirmed by Fourier transform infrared FTIR) spectroscopy, differential scanning calorimetry (DSC), and thermogravimetric analyses (TGA) techniques. The microspheres were characterized by optical microscopy, which indicated that the particles were in the size range of 30-200 mu m and scanning electron microscopy (SEM) studies revealed a smooth surface and spherical shape of microspheres. The microsphere size/size distributions were increased with the decreased stirring rates as well as GA concentration in the suspension medium. Decreasing the concentration of crosslinker increased the swelling ratio whereas extended crosslinking exhibited lowered entrapment efficiency. The in vitro drug release was controlled and extended up to 10 hr. Copyright (0 2007 John Wiley & Sons, Ltd.