Preparation of casein-chitosan sustained release microspheres containing indomethacin

ABSTRACT

A combination of polymers, casein and chitosan, was used for the preparation of sustained - release indomethacin microspheres by applying aqueous complex coacervation technique. The incorporation efficiencies of indomethacin within casein chitosan microspheres were achieved between 30.5-60.7% in the different prepared batches depending on the preparation conditions. Encapsulation efficiency was found to be 50.2 and 60.7 for 120 and 40 minutes hardening time, respectively. The results showed an increase in the mean microspheres diameter with the increase in casein concentration from 5% to 30% w/v. It was also observed that the larger the amount of initially loaded indomethacin into the microspheres that smaller was the microspher diameter. In addition, increasing chitosan concentration from 0.5 to 1.5% w/v decreased the mean microspheres diameter from 870 +/- 23 to 678 +/- 12 microm. Variation in chitosan concentration showed small effect on the particle size distribution where, increasing chitosan concentration slightly shifts the particle sizes to small diameter. Results show that the longer the stirring time [2 hours], the smaller was the microspheres size. The microspheres exhibited angle of repose values between 31- 42 and the values of the compressibility index were lower than 15% in some batches. An initial release [brust effect] of the drug is exhibited in all the prepared microspheres where 28-45% of the drug was released in the first 30 minutes in all the cases depending on the preparation conditions. Increase in casein concentration significantly decreases the rate of indomethacin release from the microspheres [P drug release. It was clear that drug release is significantly increased with increasing the initial drug loading [P drug release. The variation in chitosan concentration affect the drug release from the microspheres where lowering the concentration of chitosan leads to a significant decrease [P drug release as tested at 4, 6 and 8 hours. Microspheres separated after 40 minutes stirring time showed a significant increase [P drug release at 4, 6 and 8 hours than those separated after 2 hours of stirring. The release of indomethacin from the most promising casein-chitosan microspheres showed slow drug release were tested for apparent release kinetic model. In all cases, the release was apparently to be following diffusion model. The obtained n-values were in range of 0.394-0.494 which were slightly deviating from 0.5 in some cases