Improved intestinal delivery of salmon calcitonin by water-in-oil microemulsions

Therapeutic peptides are highly potent and specific in their functions, but difficulties in their oral administration require parallel development of viable delivery systems to improve their oral bioavailability. The objective of this study was to explore the feasibility of water-in-oil (w/o) microemulsions for improving the absorption of intraduodenally administered salmon calcitonin (sCT). The w/o microemulsions were prepared from medium chain triglyceride, Tween 80 and Span 80 or soybean phosphatidylcholine, propylene glycol and phosphate saline, and characterized by particle size and in vitro physical stability under dilution with different physiologically relevant diluents. The effects of addition of polymers such as hydroxypropylmethylcellulose and Carbomer into aqueous phase on the properties of microemulsions were assessed. sCT was efficiently encapsulated into microemulsions with nanoscaled diameter ranged from about 6 to 134 nm. As expected from the non-ionic nature of the investigated microemulsions, the physical stability, evaluated by visual inspection, the particle size and leakage percent under dilution, was found to be unaffected by pH and/or ionic strength of diluents and it was opposite for the microemulsions with ionic components. In addition, the dilution extent had a pronounced effect on the physical stability of the diluted microemulsions. The effect of polymers added into aqueous phase of the microemulsions on the absorption of the drug entrapped in microemulsions with different components was investigated. The optimized microemulsions were shown to generate substantial enhancement (up to 4-fold) of relative pharmacological activity of sCT with regard to the control solution of the drug. This indicated that the w/o microemulsions could offer the potential to significantly improve intestinal absorption of sCT. (C) 2011 Elsevier B.V. All rights reserved.