Transdermal Delivery of Captopril and Metoprolol Tartrate with Microneedles

摘要

The effect of stainless steel microneedle arrays and rollers on transcutaneous flux of captopril and metoprolol tartrate across full thickness porcine skin was studied. Captopril is an angiotensin converting enzyme (ACE) inhibitor used for the management of hypertension. It has a partition coefficient (log P) of 0.35 and a molecular weight of 216.7 g/mol. Metoprolol tartrate is a P-adrenergic blocker also used for the management of hypertension. It has a log P of 1.6 and a molecular weight of 267.3 g/mol. The properties of these anti-hypertensive agents limit the amount of the drugs that can cross the skin. To overcome this limitation, stainless steel microneedles were used to enhance transdermal delivery of these therapeutic agents. Two types of microneedle designs were used in the study- a microneedle roller and a microneedle array. In vitro diffusion studies were carried out using vertical Franz diffusion studies (PermeGear, Hellertown, PA, USA). The receptor chamber contained 12mL of phosphate buffer saline (PBS) and the donor chamber contained 1mL of captopril or metoprolol tartrate solution. The diffusion area was 1.77cm~2 and full thickness porcine skin was clamped between the two chambers. There were six untreated porcine skin samples. In the study, there were 2 Franz cells with a donor phase consisting of the same solvent as used to make the drug solutions, but without the drugs. Experiments were carried out in six replicates. Six samples served as controls. Aliquots of 1ml were withdrawn every 2 hours and analyzed with liquid chromatography. The results showed that transdermal flux values for captopril and metoprolol tartrate increased from 75.04 mug/cm~2/hr to 608.2 mug/cm~2/hr and 62.28 mug/cm~2/hr to 290.93 mug/cm~2/h respectively following the use of microneedle arrays. Transcutaneous flux for captopril increased from 19.68 mug/cm~2/hr to 1485.20 mug/cm~2/hr, whereas metoprolol tartrate flux increased from 84.64 mug/cm~2/hr to 226.08 mug/cm~2/hr after treatment of pig skin with microneedle rollers. Our results demonstrate that there was statistically significant enhancement in transdermal flux (p <0.05) of captopril and metoprolol tartrate after application of microneedle arrays and rollers. Together, these results demonstrate that stainless steel microneedle arrays and rollers can increase permeation of captopril and metoprolol tartrate across the skin. It may be possible to use this appealing alternative to create a simple and effective needle based system to deliver therapeutics across the skin.