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
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.