Colon-specific delivery tablets of sodium 4-aminosalicylic acid.
OBJECTIVE
To prepare a new oral colon-specific delivery formulation and to investigate the release profile in vitro and the colon-specific delivery property in vivo in dogs.


METHODS
Sodium 4-aminosalicylic acid was selected as the model drug. The combination of Eudragit RL30D and RS30D were used as sustained-release film, and Eudragit FS30D used as enteric film, which was expected to release drug depending on pH and time. The release profile of tablets was studied in three phosphate buffers with the pH 6.5, 7.0 or 7.4 for 12 h after a simulated gastric presoak for 2 h in 0.1 mol x L(-1) HCl. The tablets were radiolabelled with 99mTc to make their release times and positions in the gastrointestinal tract be followed using a gamma camera.


RESULTS
For the in vitro study, there was no drug released in 0.1 mol x L(-1) HCl for 2 h, and release occurred slowly when pH was above 6.5. Drug was released faster while pH was higher. For the in vivo study, the coated tablets remained intact in the upper gastrointestinal tract, and drug release began after the colonic arrival. The uncoated tablets, however, disintegrated in the stomach of the dogs rapidly.


CONCLUSIONS
The coating could protect the drug until the tablets reached the ascending colon, where drug was released slowly for over 10 h.
Li
Yan
Y
Shandong Qianfoshan Hospital, Jinan 250014, China. li_xyan@yahoo.com.cn
Li
Hong-Jian
HJ
Yang
Guo-Ren
GR
Gu
Wei-Ping
WP
Ma
Yu-Kui
YK
Zhang
Man-Hong
MH
Sun
Jie
J
Sun
Shu-Juan
SJ
D000180:Acrylic Resins / Q000737:chemistry; D000284:Administration, Oral; D010131:Aminosalicylic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004285:Dogs; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008297:Male; D013608:Tablets, Enteric-Coated
D000180:Acrylic Resins; D000995:Antitubercular Agents; D003692:Delayed-Action Preparations; D013608:Tablets, Enteric-Coated; C050528:Eudragit RS; D010131:Aminosalicylic Acid