Oral delivery of sodium cromolyn : preliminary studies in vivo and in vitro

• Published in: Pharmaceutical research 1996-02, Vol.13 (2), p.222-226
• Main Authors: LEONE-BAY, A, LEIPOLD, H, SARUBBI, D, VARIANIO, B, RIVERA, T, BAUGHMAN, R. A
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Asthmatic Agents - administration & dosage; Anti-Asthmatic Agents - pharmacokinetics; Biological and medical sciences; Biological Availability; Cromolyn Sodium - administration & dosage; Cromolyn Sodium - pharmacokinetics; Dose-Response Relationship, Drug; In Vitro Techniques; Intestinal Absorption; Intestine, Small - metabolism; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Respiratory system
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1016034913181

Herein we report the discovery of a group of derivatized alpha-amino acids that increase the oral bioavailability of sodium cromolyn. 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. 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. 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.