Dissolving microarray patches for transdermal delivery of risperidone for schizophrenia management.

Schizophrenia is a psychiatric disorder that results from abnormal levels of neurotransmitters in the brain. Risperidone (RIS) is a common drug prescribed for the treatment of schizophrenia. RIS is a hydrophobic drug that is typically administered orally or intramuscularly. Transdermal drug delivery (TDD) could potentially improve the delivery of RIS. This study focused on the development of RIS nanocrystals (NCs), for the first time, which were incorporated into dissolving microneedle array patches (DMAPs) to facilitate the drug delivery of RIS. RIS NCs were formulated via wet-media milling technique using poly(vinylalcohol) (PVA) as a stabiliser. NCs with particle size of 300 nm were produced and showed an enhanced release profile up to 80 % over 28 days. Ex vivo results showed that 1.16 ±â€¯0.04 mg of RIS was delivered to both the receiver compartment and full-thickness skin from NCs loaded DMAPs compared to 0.75 ±â€¯0.07 mg from bulk RIS DMAPs. In an in vivo study conducted using female Sprague Dawley rats, both RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) were detected in plasma samples for 5 days. In comparison with the oral group, DMAPs improved the overall pharmacokinetic profile in plasma with a ∼ 15 folds higher area under the curve (AUC) value. This work has represented the novel delivery of the antipsychotic drug, RIS, through microneedles. It also offers substantial evidence to support the broader application of MAPs for the transdermal delivery of poorly water-soluble drugs.

A five-day treatment course of zanamivir for the flu with a single, self-administered, painless microneedle array patch: Revolutionizing delivery of poorly membrane-permeable therapeutics.

Seasonal influenza virus infections cause a substantial number of deaths each year. While zanamivir (ZAN) is efficacious against oseltamivir-resistant influenza strains, the efficacy of the drug is limited by its route of administration, oral inhalation. Herein, we present the development of a hydrogel-forming microneedle array (MA) in combination with ZAN reservoirs for treating seasonal influenza. The MA was fabricated from Gantrez® S-97 crosslinked with PEG 10,000. Various reservoir formulations included ZAN hydrate, ZAN hydrochloric acid (HCl), CarraDres™, gelatin, trehalose, and/or alginate. In vitro permeation studies with a lyophilized reservoir consisting of ZAN HCl, gelatin, and trehalose resulted in rapid and high delivery of up to 33 mg of ZAN across the skin with delivery efficiency of up to ≈75% by 24 h. Pharmacokinetics studies in rats and pigs demonstrated that a single administration of a MA in combination with a CarraDres™ ZAN HCl reservoir offered a simple and minimally invasive delivery of ZAN into the systemic circulation. In pigs, efficacious plasma and lung steady-state levels of ∼120 ng/mL were reached within 2 h and sustained between 50 and 250 ng/mL over 5 days. MA-enabled delivery of ZAN could enable a larger number of patients to be reached during an influenza outbreak.

Nestorone nanosuspension-loaded dissolving microneedles array patch: A promising novel approach for "on-demand" hormonal female-controlled peritcoital contraception.

"On demand" hormonal female-controlled pericoital contraception is one strategy which could be used to minimize the impact of unintended pregnancy. Nestorone (NES) is a potent contraceptive, with relatively few side effects in comparison with other contraceptives. NES presents an attractive option for "on demand" pericoital contraceptive. Unfortunately, the drug is inactive if taken orally, but it has high progestational activity and antiovulatory potency if administered parenterally. Current drug delivery systems, such as a transdermal hydrogel are not so satisfactory. Dissolving microneedles array (DMNs) are an attractive alternative, minimally-invasive, delivery system. In this study, we report, for the first time, development of tip-loaded NES-nanosuspension (NES-NS)-loaded bilayer DMNs to deliver NES intradermally for subsequent release. NES-NS was prepared and optimised, freeze-dried and then used to fabricate DMNs using a blend of two biocompatible polymers, namely poly(vinyl alcohol) and poly(vinyl pyrrolidone). Both NES-NS and the NES-NS-loaded DMNs were fully characterised and the performance of the DMNs was evaluated in vivo using Sprague Dawley rats. Results showed that the finalised NES-NS had particle size and PDI values of 666.06 ± 1.86 nm and 0.183 ± 0.01, respectively. The NES-NS-DMNs had relatively high tips-localised drug loading (approximately 2.26 ± 1.98 mg/array) and exhibited satisfactory mechanical and insertion properties. In Sprague Dawley rats, DMNs delivered NES into the skin, with the drug then appearing in blood and rapidly reaching its maximum concentration (Cmax of 32.68 ± 14.06 ng/mL) within 1 h post-DMNs application. Plasma levels above 3.4 ng/mL were maintained for 2 days. This suggests that DMNs are a promising drug delivery system that could be used to deliver NES as an "On demand" hormonal female-controlled pericoital contraceptive.