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Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors. Ex vivo assessments showed that the MAPs delivered an average of 176 ± 60.9 μg of NGMN per MAP into excised neonatal porcine skin, representing 15.3 ± 5.3% of the loaded drug. In vivo pharmacokinetic analysis in Sprague Dawley rats demonstrated a Tmax of 4 h and a Cmax of 67.4 ± 20.1 ng/mL for the MAP-treated group, compared to a Tmax of 1 h and a Cmax of 700 ± 138 ng/mL for the intramuscular (IM) injection group, with a relative bioavailability of approximately 10% for the MAPs. The MAP-treated rats maintained plasma levels sufficient for therapeutic effects for up to 7 days after a single application. These results indicate the potential of NGMN-loaded dissolving bilayer MAPs, with further development focused on extending the release duration and improving bioavailability for prolonged contraceptive effects. [ABSTRACT FROM AUTHOR]

Microarray patches (MAPs) are currently under investigation as a self-administered, pain-free alternative used to achieve long-acting (LA) drug delivery. Cabotegravir is a potent antiretroviral that has demonstrated superior results over current pre-exposure prophylaxis (PrEP) regimens. This study aimed to apply physiologically based pharmacokinetic (PBPK) modelling to describe the pharmacokinetics of the dissolving bilayer MAP platform and predict the optimal dosing strategies for a once-weekly cabotegravir MAP. A mathematical description of a MAP was implemented into a PBPK model, and empirical models were utilised for parameter estimation. The intradermal PBPK model was verified against previously published in vivo rat data for intramuscular (IM) and MAP administration, and in vivo human data for the IM administration of LA cabotegravir. The verified model was utilised for the prediction of 300 mg, 150 mg and 75 mg once-weekly MAP administration in humans. Cabotegravir plasma concentrations >4 × protein-adjusted 90% inhibitory concentration (PA-IC90) (0.664 µg/mL) and >8 × PA-IC90 (1.33 µg/mL) were set as targets. The 75 mg, 150 mg and 300 mg once-weekly cabotegravir MAP regimens were predicted to sustain plasma concentrations >4 × PA-IC90, while the 300 mg and 150 mg regimens achieved plasma concentrations >8 × PA-IC90. These data demonstrate the potential for a once-weekly cabotegravir MAP using practical patch sizes for humans and inform the further development of cabotegravir MAPs for HIV PrEP. [ABSTRACT FROM AUTHOR]

[Display omitted] • Risedronate sodium (RDN) and alendronic acid (ALN) were formulated into dissolving (D-MAPs) and hydrogel-forming microarray patches (HF-MAPs), to investigate the transdermal delivery of the two bisphosphonates (BPs). • These MAPs were tested ex vivo before subjecting to an in vivo pharmacodynamic study employing an osteoporotic female Sprague Dawley rat model. • Therapeutic efficacy of formulated MAPs was assessed in terms of alkaline phosphatase (ALP) levels, Calcium/Phosphorus (Ca/P) ratios, and bone microarchitecture, i.e. bone volume (BV/TV %), porosity (%), trabecular thickness (Tb.th), separation (Tb.sp) and number (Tb.N). • All MAPs investigated, proved their potential as a novel, alternative treatment option for patients living with osteoporosis. As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs) are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery of BPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolving and hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawley rats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkaline phosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls. Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVX controls and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. In the distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21 % in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. This proof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternative for weekly osteoporosis management. [ABSTRACT FROM AUTHOR]

Poorly soluble drugs constitute more than 60% of currently marketed pharmaceuticals with over two‐thirds of promising new chemical entities failing to enter a clinical setting due to solubility issues. Although oral formulations have made some impact, alternative enhancement strategies for administration of such molecules are actively sought. Over the last decade, innovation on a global scale has enabled the expansion of the frontiers of microarray patches (MAPs) further than ever before. Initially designed to load low doses of hydrophilic and potent therapeutic agents, MAPs are now becoming a viable strategy for the immediate and long‐acting delivery of poorly soluble drugs through the skin. This together with the advantages of transdermal administration over the oral and parenteral routes, make of MAPs an appealing platform for the development of products with increased patient compliance. Undoubtedly, MAPs will soon become a readily available therapeutic alternative, and experts from academia, industry and regulatory bodies are working together aiming to facilitate the progression of MAPs toward safe and effective clinical use. This review aims to highlight the ability of MAPs to deliver poorly soluble actives, discuss the mechanisms behind in‐skin drug absorption, and evaluate the future direction of the field. [ABSTRACT FROM AUTHOR]