Colonic delivery of 4-aminosalicylic acid using amylose– ethylcellulose-coated hydroxypropylmethylcellulose capsules C. TULEU*, A. W. BASIT*, W. A. WADDINGTON  , P. J. ELL  & J. M. NEWTON* *Department of Pharmaceutics, The School of Pharmacy, University of London, London, UK;  Institute of Nuclear Medicine, University College London, The Middlesex Hospital, London, UK Accepted for publication 10 May 2002 SUMMARY Background: 4-Aminosalicylic acid has the potential for use in the treatment of diseases of the colon. Aim: To assess the feasibility of delivering 4-aminosal- icylic acid directly to the colon using a hydroxypro- pylmethylcellulose 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 99m Tc 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. I NTRODUCTION The colon is susceptible to a variety of disease states, of which the chronic inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, are the most serious. The anti-inflammatory drug 5-aminosalicylic acid (5-ASA) has been widely used in the treatment of such diseases. 1, 2 The isomeric drug, 4-aminosalicylic acid (4-ASA), has been employed since the 1940s as a treatment for tuberculosis. More recently, however, various authors have shown that rectal administration of 4-ASA is an effective alternative to 5-ASA in the treatment of ulcerative colitis. 2–9 The rectal route, however, is not convenient or acceptable for most patients, and therefore such patients would benefit from an oral alternative to chronic enema therapy. Orally administered anti-inflammatory drugs are largely absorbed before reaching the colon, resulting in a significant degree of systemic activity and a limited local effect within the colon. The systemic adverse effects of 4-ASA, in common with other salicylates, are well documented and include gastrointestinal disturbances (nausea, vomiting, abdom- inal pain, diarrhoea and anorexia), hypersensitivity reactions (fever, various types of skin eruptions) and other untoward effects, 10 thereby restricting its use in Ó 2002 Blackwell Science Ltd 1771 Correspondence to: Professor J. M. Newton, Department of Pharmaceutics, The School of Pharmacy, University of London, 29 ⁄ 39 Brunswick Square, London WC1N 1AX, UK. E-mail: michael.newton@ams1.ulsop.ac.uk Aliment Pharmacol Ther 2002; 16: 1771–1779. doi:10.1046/j.0269-2813.2002.01327.x