Statistical design and optimization of ketorolac tromethamine gastroretentive multiparticulate delivery system

Abstract

The aim of the present research is to design and optimize floating multiparticulate drug delivery system of Ketorolac tromethamine (KT) so as to reduce its irritant effect on the gastric mucosa. Extrusion and spheronization process were used to prepare a drug-containing core pellets. A 3 level 2 experimental factor design was used to examine the effect of the amount of Eudragit RS 100, effervescent agent (NaHCO3: HPMC K4M) on floating lag time and drug release in 6 h. Fourier Transform Infra-Red (FTIR) spectrum, physical characterization, particle size distribution analysis, scanning electron microscopy, floating studies and in vitro drug release studies of prepared floating pellets were evaluated. The study reveals the significant effect of the amount of Eudragit RS 100 and NaHCO3: HPMC K4M on floating lag time and drug release. The optimized batch showed floating lag time of 3.2 min and 95.15% average drug release in 6 hours. 80–95% of pellets remained floating for up to 6 h. All the batches showed excellent flow properties having an angle of repose in the range 29.85±0.20 to 21.60±0.50, Carr’s index and Hausner’s ratio in the range of 14.49±0.26% to 7.54±0.32% and 1.08±0.04 to 1.16±0.7 respectively. The sustained release gastroretentive floating pellets of Ketorolac tromethamine were obtained and could be effectively used in the delivery of drug with less irritant effect on the gastric mucosa.