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.
Integrated Product Development, Dr. Reddy's Laboratories Ltd., Hyderabad, Andhra Pradesh, India. mangeshcd@yahoo.co.uk
Mangesh C
MC
Deshpande
Vobalaboina
V
Venkateswarlu
Arunkumar H
AH
Mantri
Sandeep T
ST
Gadewar
D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004285:Dogs; D004343:Drug Implants; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000097:blood* / Q000378:metabolism*; D065089:Glycoside Hydrolase Inhibitors; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008747:Methylcellulose / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D019518:Postprandial Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D000520:alpha-Glucosidases / Q000378:metabolism
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004040:Dietary Carbohydrates; D004343:Drug Implants; D065089:Glycoside Hydrolase Inhibitors; D011108:Polymers; C045621:miglitol; D017485:1-Deoxynojirimycin; C013517:ethyl cellulose; D052216:Glucagon-Like Peptide 1; D002482:Cellulose; D008747:Methylcellulose; D000520:alpha-Glucosidases