Buccal absorption of enalapril and lisinopril

Objective: The buccal absorption of captopril does not exhibit the classical pH/partition hypothesis, suggesting that mechanisms other than passive diffusion are involved in its absorption; animal studies have suggested that a peptide carrier-mediated transport system may be responsible for its absorption. The present study evaluated the effects of pH on octanol partitioning, and on the buccal absorption of enalapril and lisinopril, using in vitro techniques and buccal partitioning in human volunteer subjects.

Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs

Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds.