Development and Evaluation of a Double-phase Multiple-unit Dosage form for Enhanced Insulin Intestinal Delivery

Author(s): Suzette de Bruyn, Clarissa Willers, Dewald Steyn, Jan Steenekamp, Josias Hamman*.

Journal Name: Drug Delivery Letters

Volume 8 , Issue 1 , 2018

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Graphical Abstract:


Background: The oral route is the most preferred route of administration for selfmedication, but poor membrane permeability and pre-systemic degradation are key challenges that need to be addressed.

Objective: The purpose of this study was to develop and evaluate a double-phase, multiple-unit dosage form for enhanced delivery of insulin across the gastrointestinal tract epithelium. The dosage form was designed to provide increased membrane permeation by opening of tight junctions during the first phase followed by insulin delivery during the second phase.

Methods: Different beads were prepared by means of extrusion-spheronisation. Combinations of different beads constituted the double-phase drug delivery systems. The one type of bead contained insulin as active ingredient and chitosan as mucoadhesive agent, while the other bead formulations contained each one of the following drug absorption enhancers: a bile salt mixture, sodium glycocholate, Aloe vera whole leaf extract or Aloe vera gel. The insulin delivery performance of the different doublephase delivery systems was evaluated across excised pig intestinal tissues in a Sweetana-Grass diffusion apparatus.

Results: Initial exposure of the excised pig intestinal tissues to the absorption enhancer containing beads (first phase) was associated with enhanced intestinal transport of insulin (second phase) when compared to the control group. The insulin permeation enhancement effect across excised pig intestinal tissue was statistically significant in the case of pre-exposure to A. vera whole leaf extract and A. vera gel containing beads.

Conclusion: Several double-phase multiple-unit drug delivery systems have the potential to effectively deliver insulin across the gastrointestinal epithelium.

Keywords: Aloe vera, bile salt, chitosan, extrusion-spheronisation, insulin, paracellular permeation, permeation enhancement, sodium glycocholate, tight junction.

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Article Details

Year: 2018
Page: [52 - 60]
Pages: 9
DOI: 10.2174/2210303107666170928125212
Price: $25

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