PURPOSE: Herein we report the discovery of a group of derivatized alpha-amino acids that increase the oral bioavailability of sodium cromolyn. METHODS: We prepared three N-acylated alpha-amino acids and used these compounds to demonstrate the oral delivery of cromolyn in an in vivo rat model. In vitro experiments, including permeation studies and near infrared spectroscopy, were also performed to initiate an understanding of the mechanism by which these compounds facilitate cromolyn oral delivery. RESULTS: Following oral administration to rats of solutions containing a combination of cromolyn and the delivery agent, significant systemic plasma concentrations of the drug were detected. In vitro studies suggest that absorption of the drug across the gastrointestinal membrane is a passive process. CONCLUSION: The absolute oral bioavailability of sodium cromolyn in the rat model is estimated to be approximately 5%. Preliminary mechanistic studies suggest that a complex of the cromolyn/delivery agent facilitates permeation across/through the membrane.
PURPOSE: Herein we report the discovery of a group of derivatized alpha-amino acids that increase the oral bioavailability of sodium cromolyn. METHODS: We prepared three N-acylated alpha-amino acids and used these compounds to demonstrate the oral delivery of cromolyn in an in vivo rat model. In vitro experiments, including permeation studies and near infrared spectroscopy, were also performed to initiate an understanding of the mechanism by which these compounds facilitate cromolyn oral delivery. RESULTS: Following oral administration to rats of solutions containing a combination of cromolyn and the delivery agent, significant systemic plasma concentrations of the drug were detected. In vitro studies suggest that absorption of the drug across the gastrointestinal membrane is a passive process. CONCLUSION: The absolute oral bioavailability of sodium cromolyn in the rat model is estimated to be approximately 5%. Preliminary mechanistic studies suggest that a complex of the cromolyn/delivery agent facilitates permeation across/through the membrane.
Authors: Xuan Ding; Parshuram Rath; Robert Angelo; Thomas Stringfellow; Elizabeth Flanders; Steven Dinh; Isabel Gomez-Orellana; Joseph R Robinson Journal: Pharm Res Date: 2004-12 Impact factor: 4.200