Xanthan and galactomannan (from M. scabrella) matrix tablets for oral controlled delivery of theophylline

Directly compressed theophylline tablets, containing commercial xanthan (X) (Keltrol®) and a highly hydrophilic galactomannan (G) from the seeds of Mimosa scabrella (a brazilian leguminous tree called bracatinga) as release-controlling agents, were obtained. Gums were used at 4, 8, 12.5 and 25% (w/w), either alone or in mixture (X:G 1:1). During galactomannan extraction process, the biopolymer was dried in a scale up, by vacuum oven (VO) or spray dryer (SD). The in vitro drug release was evaluated at different time intervals during 8 h using apparatus 1 (USP 26) at 100 rpm. The pH of the dissolution medium (1.4) was changed to 4.0 and 6.8 after 2 and 3 h, respectively. Tablets containing G(SD) resulted in more uniform drug release than G(VO) ones, due to their smaller particle size. The drug release decreased with the increase of polymer concentration and all formulations at 25% w/w of gums showed excessive sustained release effect. The matrices made with alone X showed higher drug retention for all concentrations, compared with G matrices that released the drug too fast. The XG matrices were able to produce near zero-order drug release. The XG(SD) 8% tablets provided the required release rate (about 90% at the end of 8 h), with zero-order release kinetics. Tablets containing G(VO) in low concentration showed a complete erosion, while the others demonstrated fast hydration and swelling in contact with the dissolution medium. The release mechanism was a combination of difusion and relaxation. The relative importance of these two processes varied with matrix composition. The XG(SD) 8% matrix showed higher contribution of polymer relaxation.