Ring inserts as a useful strategy to prepare tip-loaded microneedles for long-acting drug delivery with application in HIV pre-exposure prophylaxis

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The role of microneedle array patches (MAPs) and, in particular, dissolving MAPs in transdermal drug delivery has increased exponentially over the last decade. MAPs are able to form drug depots in the viable skin from where poorly soluble drugs dissolve in a long-acting fashion, showing promise in the management of multiple diseases. The manufacture of these systems can present some challenges, including the presence of bubbles in the baseplates and consequent lack of uniformity in microneedle formation and drug content. Here, we present a simple method based on ring inserts to produce tip-loaded MAPs using the antiretroviral drug cabotegravir sodium (CAB). The obtained MAPs presented a high uniformity in terms of microneedle formation, and a suitable insertion capability, as per the mechanical characterisation performed. An optimisation based on design of experiments revealed that centrifugation parameters had a significant impact on the skin deposition of the MAPs in excised neonatal porcine skin using Franz cells, with values ranging from 62.24 ± 47.13 µg to 174.13 ± 41.10 µg of CAB. Pharmacokinetic studies carried out in rats evidenced the capacity of the MAPs to maintain therapeutic plasma levels of CAB for 14 days, with Tmax values reached between 5 and 8 days.