In vivo swelling kinetics of a series of hydrogel polymers in the gastrointestinal tract of the cannulated canine

Hydrogels for oral controlled drug delivery must swell at a predictable rate as they move through the various regions of the gastrointestinal tract. Residence time in these different regions, coupled with available water and local environmental conditions, can potentially influence the rate and extent of swelling.; The objective of this study is to regio-specifically study the in-vivo swelling behavior of four hydrogel polymers in the duodenal and ileal regions of the small intestine of cannulated canines in fasted and fed states. The four polymers were hydroxypropyl methyl cellulose, carboxylmethyl cellulose sodium salt, Carbopol 974P{dollar}rmsp{lcub}TM{rcub}{dollar}, and Noveon AA1{dollar}rmsp{lcub}TM{rcub}{dollar} (polycarbophil). The fed state was generated by gavage feeding of either water or Pulmocare{dollar}rmsp{lcub}TM{rcub}{dollar}. Atropine sulfate, a naturally occurring antimuscarinic known to inhibit gastric and duodenal secretions, administered intravenously allowed us to study the effect of these secretions on the polymer swelling.; Information gathered from these in-vivo studies, combined with data previously reported in the literature and data generated by a series of in-vitro studies, enabled us to design a computer generated kinetic model to describe polymer swelling and movement of fluid, spatially and temporally, through the gastrointestinal tract using STELLA{dollar}rmsp{lcub}TM{rcub}{dollar}, a simulation software package for handling compartment models.; For each of the hydrogels studied, swelling was observed to be greater in the duodenum than the ileum. In-vivo swelling appears not to be strongly influenced by the fluid ingested per os nor by the gastric and duodenal secretions. In addition, the extent of swelling was seen to be independent of the timing of the insertion or ingestion of the polymer relative to the migrating myoelectric complex (MMC). Through intravenous injections of atropine sulfate to shut down gastric and duodenal secretions, in vivo polymer swelling was seen not to be affected by the presence or absence of these gastrointestinal secretions. We therefore propose that the fluid necessary for polymer swelling is primarily derived from the aqueous mucous gel coating the epithelial cells lining the small intestine. Differences in swelling rate and extent in ileal and duodenal regions may be due to differences in the amount and thickness of mucous in the two regions.