Polymeric Microarray Patches for Enhanced Transdermal Delivery of the Poorly Soluble Drug Olanzapine

Abstract

Transdermal drug delivery is an alternative route of administration that offers avoidance of the associated drawbacks of orally and parenterally administered hydrophobics. However, owing to the extremely specific set of physicochemical characteristics required for passive transdermal drug permeation, the development of marketed transdermal products containing poorly soluble drugs has been severely limited. Microarray patches (MAPs) are a type of transdermal patch that differ from the traditional patch design due to the presence of tiny, micron-sized needles that permit enhanced drug permeation on their application surface. To date, MAPs have predominantly been used to deliver hydrophilic compounds. However, this work challenges this trend and focuses on the use of MAPs, in combination with commonly utilized solubility-enhancing techniques, to deliver the hydrophobic drug olanzapine (OLP) across the skin. Specifically, cyclodextrin (CD) complexation and particle size reduction were employed in tandem with hydrogel-forming and dissolving MAPs, respectively. In vivo experimentation using a female Sprague-Dawley rat model confirmed the successful delivery of OLP from hydrogel-forming MAPs (C max = 611.13 ± 153.34 ng/mL, T max = 2 h) and dissolving MAPs (C max = 690.56 ± 161.33 ng/mL, T max = 2 h) in a manner similar to that of oral therapy in terms of the rate and extent of drug absorption, as well as overall drug exposure and bioavailability. This work is the first reported use of polymeric MAPs in combination with the solubility-enhancing techniques of CD complexation and particle size reduction to successfully deliver the poorly soluble drug OLP via the transdermal route. Accordingly, this paper provides significant evidence to support an expansion of the library of molecules amenable to MAP-mediated drug delivery to include those that exhibit poor aqueous solubility.

Novel SmartReservoirs for hydrogel-forming microneedles to improve the transdermal delivery of rifampicin

“…(2) Furthermore, the insertion characteristics of the MNs into the skin Parafilm s M model were examined using an EX-101 optical coherence tomography (OCT) microscope (Michelson Diagnostics Ltd, Kent, UK). 18,64 OCT images were captured to visualise the depth of needle insertion, and ImageJ s software (National Institutes of Health, Bethesda, MD, USA) was utilised to calculate the precise insertion depth.…”

“…15 While oral antibiotic treatment is usually prescribed, it is not without drawbacks. [16][17][18] Challenges can arise from drug stability in the gastrointestinal tract (GIT), along with the disruption of the GIT microbiome which could result in antimicrobial resistance. [18][19][20] Various strategies have been explored to target deep skin tissue and systemic infections whilst reducing potential side effects.…”

“…[16][17][18] Challenges can arise from drug stability in the gastrointestinal tract (GIT), along with the disruption of the GIT microbiome which could result in antimicrobial resistance. [18][19][20] Various strategies have been explored to target deep skin tissue and systemic infections whilst reducing potential side effects. These approaches have included the use of different nanocarriers, such as extracellular vesicles, liposomes, ethosomes, lipid and polymer nanoparticles within topical formulations.…”

“…40 HF-MNs, as their name suggests, are micron-scale needles prepared by a crosslinking reaction from an aqueous mixture of different swellable polymers and supported by a baseplate. 18,[41][42][43][44][45] HF-MNs are drug-free as the active ingredient is contained in a reservoir affixed on the top of the base of the HF-MNs. HF-MNs have the capacity to circumvent the outermost layer of the skin, known as the stratum corneum, without causing pain or lipohypertrophy as seen with repeated IV injections.…”

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies

“… 32 , 33 MAPs are micron-sized (less than 1 mm in length), minimally invasive devices that breach the outermost layer of the skin and the stratum corneum , creating micron-sized pores in the skin and facilitating intradermal delivery of drugs with minimal pain and no bleeding. 34 − 36 Dissolving MAPs are composed of water-soluble polymers that incorporate the drug within the MAPs themselves and dissolve once inserted into the skin. 32 , 37 Dissolving MAPs can achieve controlled drug release due to the dissolution rate of the constituted polymer.…”