Targeting enteral endocrinal L-cells with dietary carbohydrates, by increasing the availability of miglitol in the intestinal lumen, leads to multi-fold enhancement of plasma glucagon-like peptide-1 levels in non-diabetic canines.

The principle aim of this study was to design a controlled release (CR), bioadhesive formulation of miglitol (in form of pellets) which would regulate the post-prandial glucose levels via reversible inhibition of α-glucosidase enzyme as well as by modulating the glucagon-like peptide-1 (GLP-1) pathway in non-diabetic canines. A multilayered pellet formulation which was both bioadhesive (because of hydroxy propyl methyl cellulose polymer) and CR (because of the ethyl cellulose layer) was formulated. We report a novel finding that the CR formulation of miglitol (S3) induced a 2.2-fold elevation in the C(max) as well as the overall AUC(0-24) of GLP-1 values in comparison to the non-CR (immediate release (IR) formulation). The S3 formulation also resulted in better, steady, and prolonged control of glucose levels over a time period of 7 h in comparison to the IR formulation possibly due to combination of both, prolonged inhibition of the α-glucosidase enzyme and enhanced plasma GLP-1 levels. The S3 formulation was stable with no changes in the dissolution profiles at both of the stability conditions tested, 25°C/60% RH and 40°C/75% RH. Aqueous polymeric coating of the pellets (in contrast to coating using organic solvents) resulted morphologically in a uniform polymeric film and also releases profiles with lower burst effect. Curing played a significant role in determining release profile of the pellets, prepared by aqueous polymeric coating method.