Colonic delivery of 4-aminosalicylic acid using amylose-ethylcellulose-coated hydroxypropylmethylcellulose capsules.
BACKGROUND
4-Aminosalicylic acid has the potential for use in the treatment of diseases of the colon.


OBJECTIVE
To assess the feasibility of delivering 4-aminosalicylic acid directly to the colon using a hydroxypropylmethylcellulose capsule coated with a mixture of amylose, a polysaccharide metabolized by bacterial enzymes in the colon, and ethylcellulose.


METHODS
Seven healthy male volunteers received, on three separate occasions, an uncoated or amylose-ethylcellulose-coated hydroxypropylmethylcellulose capsule containing 4-aminosalicylic acid Na (550 mg), or an intravenous injection of 4-aminosalicylic acid Na (135 mg). The capsules were radiolabelled with 99mTc to allow their positions in the gastrointestinal tract to be followed using a gamma camera. Plasma and urine samples were collected and assayed for 4-aminosalicylic acid and metabolite concentrations.


RESULTS
The uncoated capsules broke down within 10 min in the stomach, allowing rapid and complete absorption of the drug. The coated capsules remained intact in the upper gastrointestinal tract, and had a median gastric emptying time of 61 min (interquartile range, 77 min) and a median colon arrival time of 363 min (interquartile range, 185 min). For the coated capsules, only the metabolite was detected in the plasma and/or urine after the capsules had reached the colon.


CONCLUSIONS
The specific coating protected the drug until the capsule reached the colon, where 4-aminosalicylic acid was slowly released and absorbed. Thus, such a formulation has the potential for use in the treatment of inflammatory bowel disease.
Tuleu
C
C
Department of Pharmaceutics, The School of Pharmacy, University of London, UK.
Basit
A W
AW
Waddington
W A
WA
Ell
P J
PJ
Newton
J M
JM
D000328:Adult; D010131:Aminosalicylic Acid / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D000688:Amylose; D002214:Capsules; D002482:Cellulose / Q000031:analogs & derivatives*; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004064:Digestive System / Q000000981:diagnostic imaging / Q000378:metabolism; D005240:Feasibility Studies; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D006801:Humans; D065347:Hypromellose Derivatives; D007275:Injections, Intravenous; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives*; D011877:Radionuclide Imaging; D013667:Technetium
D002214:Capsules; D003692:Delayed-Action Preparations; D005765:Gastrointestinal Agents; D065347:Hypromellose Derivatives; D010131:Aminosalicylic Acid; D013667:Technetium; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose; D000688:Amylose