Development of a double phase dosage form for enhanced peptide drug delivery
De Bruyn, Suzette
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Parenteral administration remains the most utilised route of administration for therapeutic peptides due to low intestinal epithelial permeability. However, the most convenient and popular route of drug administration remains the oral route. Oral delivery of protein and peptide drugs encounters challenges such as poor penetration of intestinal mucosa and pre-systemic enzymatic degradation. The former can be overcome with the inclusion of effective and safe absorption enhancing agents in dosage forms. In previous studies, both Aloe vera leaf materials and bile salts have shown the capability of increasing drug transport across in vitro intestinal epithelial models. The purpose of this study was to develop and evaluate a double phase drug delivery system for effective oral insulin delivery. Spherical beads were prepared by means of extrusion spheronisation containing insulin as active ingredient and chitosan as muco-adhesive agent. Four other bead formulations were prepared by means of extrusion spheronisation, each containing a different drug absorption enhancing agent, which included Aloe vera whole leaf, Aloe vera gel, a bile salt mixture (50% sodium cholate acid and 50% sodium deoxycholate) and a single bile salt (sodium glycocholate). The physical and muco-adhesive properties of the different bead formulations were evaluated. Mixtures of the beads containing insulin with beads containing an absorption enhancer were loaded into hard gelatin capsules to prepare four different double phase drug delivery systems. The insulin delivery performance of the double phase drug delivery systems was evaluated across excised pig intestinal tissues in a Sweetana-Grass diffusion apparatus. All the bead formulations complied with the specified requirements regarding physical properties and showed relatively narrow size distribution values. Inclusion of chitosan pronouncedly improved the muco-adhesive properties of the beads. All the double phase drug delivery systems showed enhanced transport of insulin across excised pig intestinal tissues, which was significantly higher than that of the control group (insulin alone) when pre-exposed to A. vera whole leaf containing beads.
- Health Sciences