Effects of product formulation on in vitro activity of pancreatic enzymes

The lipase activity of two enteric-coated and two uncoated pancreatic enzyme formulations was evaluated in vitro at different pH values and compared with postprandial duodenal pH data in cystic fibrosis patients. Lipase activity was measured over a pH range of 4-8 in four formulations: Viokase tablets and Viokase powder (Viobin), Cotazym-S (Organon), and Pancrease enteric-coated spherules (McNeil). A pH-stat technique was used in which the amount of hydroxyl ion that must be added to maintain a preset pH value is measured to determine the amount of lipase substrate (tributyrin) that is split into butyric acid. At least three determinations of activity were made at each pH. Six capsules of each enteric-coated formulation were subjected to disintegration testing at various pH values. These data were then compared with data available for postprandial duodenal pH in patients with cystic fibrosis. The lipase activity of all formulations studied decreased when pH decreased, especially when the pH was below 5.75. At a pH value between 5 and 5.5, which represents the postprandial duodenal pH in cystic fibrosis patients, activity was reduced 50% or more for all formulations tested. The two enteric-coated products displayed no activity at pH 5.5 and below because the coating did not dissolve in this pH range. Lipase activity in enteric-coated pancreatic enzyme preparations is limited because the enteric coating of these products dissolves slowly in the duodenal pH range (5-5.75) that is found in patients with cystic fibrosis.