ORAL DELIVERY OF SODIUM CROMOLYN - PRELIMINARY STUDIES IN-VIVO AND IN-VITRO

Purpose. Herein we report the discovery of a group of derivatized alph a-amino acids that increase the oral bioavailability of sodium cromoly n. Methods. We prepared three N-acylated alpha-amino acids and used th ese compounds to demonstrate the oral delivery of cromolyn in an in vi vo rat model. In vitro experiments, including permeation studies and n ear infrared spectroscopy, were also performed to initiate an understa nding of the mechanism by which these compounds facilitate cromolyn or al delivery. Results. Following oral administration to rats of solutio ns containing a combination of cromolyn and the delivery agent, signif icant systemic plasma concentrations of the drug were detected. In vit ro studies suggest that absorption of the drug across the gastrointest inal membrane is a passive process. Conclusion. The absolute oral bioa vailability of sodium cromolyn in the rat model is estimated to be sim ilar to 5%. Preliminary mechanistic studies suggest that a complex of the cromolyn/delivery agent facilitates permeation across/through the membrane.