0000000000038323
AUTHOR
Raimar Löbenberg
Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Enalapril
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the marketing authorization of immediate-release, solid oral dosage forms containing enalapril maleate are reviewed. Enalapril, a prodrug, is hydrolyzed by carboxylesterases to the active angiotensin-converting enzyme inhibitor enalaprilat. Enalapril as the maleate salt is shown to be highly soluble, but only 60%-70% of an orally administered dose of enalapril is absorbed from the gastrointestinal tract into the enterocytes. Consequently, enalapril maleate is a Biopharmaceutics Classification System class III substance. Because in situ conversion of the maleate salt to the sodium salt is sometim…
Mechanistic understanding of underperforming enteric coated products: Opportunities to add clinical relevance to the dissolution test.
Over the last 70 years several cases of in vivo failure of enteric coated (EC) formulations have been reported. The observed failures seem to be due to the slower than expected in vivo performance of EC products. Upon reaching the intestinal lumen, the dosage form is exposed to a bicarbonate buffered environment at much lower interfacial buffering capacity compared to those applied in compendial phosphate buffers. Hence, there is an urgent need to understand the behavior of EC products in bicarbonate buffer (BCB) and to revaluate the current dissolution methods used for such products. The current pilot study mechanistically investigated the performance of five EC products available in the C…