Enzyme Content and Acid Stability of Enteric-Coated Pancreatic Enzyme Products In Vitro

Abstract

Pancreatic enzymes are prescribed routinely for pancreatic insufficiency. In the current health care environment, drug substitution is commonly performed although there is no proof of therapeutic or bioequivalence for these products. The purpose of this in vitro, prospective study was to evaluate the enzyme contents and dissolution of various capsules of pancreatic enzyme using current United States Pharmacopoeia (USP) methodology. Nine different pancreatic enzyme products were purchased on the market and supplied to Irvine Analytical Laboratories (IAL) (Irvine, CA). All test products were maintained in the laboratory environment, at room temperature, throughout the testing period by IAL. USP procedures for assay and dissolution testing of pancrelipase delayed-release capsules, as described in the latest USP supplement were observed during product testing, including determination of amylase, lipase, and protease activity. In addition, a point assay with measurement of lipase after dissolution in simulated gastric fluid pH of 1.0 for 1 hour and then dissolution in pH 6 phosphate buffer for 30 minutes performed in accordance with USP guidelines. Assay results of amylase, protease, and lipase from the 9 tested products are within USP specified limits. The percentage of label claim for these enzymes was higher than depicted in their label except for one drug batch. However, the percentage of lipase activity after dissolution varied with 2 of 3 batches of 1 drug not dissolving, and 1 batch of another drug, revealing only 8% lipase activity in the USP dissolution test. While assay of pancreatic enzymes reveal they were equal to their USP claims regarding their enzyme content, not all pancreatic enzyme replacements are equal in their release of lipase activity according to USP requirements. The findings maybe clinically seen with therapeutic failures of enzyme products. The FDA has recently decreed that all pancreatic enzyme products will require an approved NDA as differences in pharmaceutical quality have been identified in this product. Thus, it is considered that substitution of these products maybe questionable. Things are seldom what they seem- not all pancreatic enzyme replacements are equal. Further studies are warranted to investigate dissolution characteristics.