Preparation and evaluation of indomethacin loaded alginate microspheres

Indomethacin-loaded alginate microspheres were prepared by the ionic cross linking technique using calcium chloride. The effect of calcium chloride concentration was evaluated with respect to the size, entrapment efficiency and shape (sphericity) of the particles. The entrapment efficiency and in vitro release profiles were found to be altered by changing various formulation parameters. The desired indomethacin in vitro release profile (as per USP specifications for extended release formulations) was obtained from microspheres prepared from gel containing 2% of sodium alginate and 2% of methyl cellulose hardened in 3% calcium chloride solution. The kinetic modeling of the release data indicated that indomethacin release from alginate microspheres followed Higuchi model and the release mechanism was diffusion. FTIR study confirmed the absence of any drug polymer interaction. DSC and XRD studies revealed that the crystallinity of the drug decreased when loaded in the alginate microspheres. The pharmacokinetic parameters were also evaluated in rabbits using HPLC technique and it was found that indomethacin loaded microspheres showed increased t1/2 and AUC values. Ke value was less than that of pure drug. This confirmed controlled release of the drug from microspheres leading to more residence time in the body within the therapeutic range providing longer duration of action which is preferable in chronic treatment of the diseases.Key words: indomethacin controlled release Fickian diffusion pharmacokinetics.