In vitro comparative study of three pancreatic enzyme preparations: dissolution profiles, active enzyme release and acid stability

• Published in: Alimentary pharmacology & therapeutics Vol. 27; no. 3; pp. 283 - 292
• Main Authors: ALOULOU, A., PUCCINELLI, D., SARLES, J., LAUGIER, R., LEBLOND, Y., CARRIÈRE, F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2008; Blackwell
• Subjects: Amylases - analysis; Animals; Biological and medical sciences; Biological Availability; Chymotrypsin - analysis; Digestive system; Duodenum - metabolism; Exocrine Pancreatic Insufficiency - drug therapy; Exocrine Pancreatic Insufficiency - metabolism; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Agents - pharmacokinetics; Humans; Hydrogen-Ion Concentration; Lipase - analysis; Medical sciences; Microspheres; Pancreatic Extracts - pharmacokinetics; Pancrelipase - pharmacokinetics; Pharmacology. Drug treatments; Solubility; Tablets, Enteric-Coated; Stability; Acids; Enzyme; Preparation; Pancreas; Dissolution; In vitro; Physicochemical properties; Comparative study; Release
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2007.03563.x

Summary Background  Various pancreatic enzyme preparations are used for the treatment of pancreatic insufficiency but their bioequivalence is often unknown. Aim  To determine in vitro the pH‐dependent release and acid resistance of enzymes from three commercially available pancreatin capsules, two containing enteric‐coated (Creon 25000; Eurobiol 25000) and one uncoated (Eurobiol 12500) microspheres. Methods  Dissolution experiments were performed at pH values ranging from 4.0 to 5.8. Lipase, chymotrypsin and amylase activities were measured in the solution as a function of time. Results  Eurobiol 25000 started to release its enzymes significantly at pH 5.0 (t1/2 = 71 min), whereas the enzymes from Creon 25000 were only released at higher pH value (5.4; t1/2 = 49.2 min). Unlike chymotrypsin, lipase and amylase were highly sensitive to acidic conditions at the lowest pH values tested. Both enzymes were also found to be sensitive to proteolytic inactivation at the highest pH values tested. Overall, Eurobiol 25000 released higher amounts of active amylase and lipase than Creon 25000 at the pH values usually found in duodenal contents. The uncoated Eurobiol 12500 preparation was, however, the only one that could immediately release rather high levels of active chymotrypsin and lipase at low pH (4.5). Conclusion  These findings suggest that pH‐sensitive enteric‐coated pancreatin products containing similar amounts of enzymes might not be bioequivalent depending on the pH of duodenal contents.