Semi-interpenetrating polymer network microspheres of gelatin and sodium carboxymethyl cellulose for controlled release of ketorolac tromethamine

Semi-interpenetrating polymer network (IPN) microspheres of natural polymers, viz., gelatin and sodium carboxymethyl cellulose (NaCMC) were prepared by using glutaraldehyde (GA) as a crosslinker. Ketorolac tromethamine (KT), an anti-inflammatory and analgesic agent, was successfully encapsulated into IPN microspheres. Various formulations were prepared by varying the ratio of gelatin and NaCMC, % drug loading, and amount of GA. Microspheres were characterized by Fourier transform infrared spectroscopy (FTIR) to understand the formation of IPN structure and to confirm the absence of chemical interactions between drug, polymer, and crosslinking agent. Scanning electron microscopy (SEM) was used to study the surface morphology of the microspheres. SEM showed that particles have slightly rough surfaces. Particle size as measured by using laser light scattering technique gave an average size ranging from 247 to 535 pm. Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) studies were performed to understand the crystalline nature of the drug after encapsulation into IPN microspheres. Drug encapsulation of up to 67% was achieved as measured by the UV method. Both equilibrium and dynamic swelling experiments were performed in water. Diffusion coefficients (D) of water transport through the microspheres were determined using an empirical equation. Values of D decrease with increasing crosslinking as well as increasing content of NaCMC in the matrix. In vitro release studies indicated a dependence of release rate on both the extent of crosslinking and the amount of NaCMC used to produce microspheres, but slow release was extended up to 10 It. Cumulative release data were fitted to an empirical equation to compute diffusional exponent (n), which indicated the non-Fickian trend for drug release. (c) 2006 Published by Elsevier Ltd.