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.

Starting slow: the effects of response-switching frequency on patterns of cardiovascular reactivity

Research findings suggest that switching between competing response sets can be resource demanding. The current study focused on concurrent health-relevant physiological effects of task switching by assessing cardiovascular response at varying levels of switch frequency. The participants performed a response-switching task at three different levels of response set switching frequency (low, medium and high) while measurements of blood pressure and heart rate were taken. One group was exposed to response-switching frequency conditions in the order low → medium → high, while the other group was exposed to the same task conditions in the reverse order (i.e. high → medium → low). The results showed that the participants in the low → medium → high switch frequency group recovered faster from initially heightened systolic blood pressure when compared with participants in the high → medium → low group. It is concluded that the results point to a physiological "carry over" effect associated with beginning a task at rapid response switching frequency levels, and suggest the importance of habituation to task demands as a means of offsetting potentially unhealthy levels of reactivity. Implications for modern work environments are discussed.