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Hydrogel-forming microarray patches (HF-MAPs) offer minimally invasive, pain-free and prolonged drug delivery. These devices are designed to be self-administered and self-disabling, avoiding contaminated sharps waste generation. Cabotegravir sodium (CAB-Na) is a poorly soluble anti- human immunodeficiency virus (HIV) drug for the treatment and pre-exposure prophylaxis of HIV infection that lends itself to depot formation following intradermal delivery but presents significant challenges when delivered via HF-MAPs, whose nature is aqueous. Herein, we have investigated, for the first time, the use of hydroxypropyl-β-cyclodextrin (HP-β-CD) to enhance the solubility of CAB-Na, and its effect on intradermal delivery via HF-MAPs. Accordingly, tablet reservoirs containing CAB-Na and HP-β-CD were formulated. These novel reservoirs were combined with two different HF-MAP formulations (MAP1 (Gantrez S97® + poly (ethylene glycol) 10,000 + Na2CO3) and MAP2 (poly (vinyl pyrrolidone) 58 kDa + poly (vinyl alcohol) 85–120 kDa + citric acid)) to form fully integrated MAP devices which were tested in both ex vivo and in vivo settings. Ex vivo skin deposition results for MAP1 and MAP2 showed that 141 ± 40 μg and 342 ± 34 μg of CAB-Na was deposited into 0.5 cm2 of excised neonatal porcine skin after 24 h, respectively. Based on these findings, the in vivo pharmacokinetics of MAP2 were investigated over 28 days using a Sprague-Dawley rat model. After 24 h patch application, MAP2 demonstrated an extended drug release profile and an observed Cmax of 53.4 ± 10.16 μg/mL, superior to that of an FDA-approved CAB-nanosuspension administered via intramuscular application (Cmax of 43.6 ± 5.3 μg/mL). Consequently, this tablet integrated MAP device is considered to be a viable option for the intradermal delivery of hydrophobic anti-HIV drugs.

Implantable drug-eluting devices that provide therapeutic cover over an extended period of time following a single administration have potential to improve the treatment of chronic conditions. These devices eliminate the requirement for regular and frequent drug administration, thus reducing the pill burden experienced by patients. Furthermore, the use of modern technologies, such as 3D printing, during implant development and manufacture renders this approach well-suited for the production of highly tuneable devices that can deliver treatment regimens which are personalised for the individual. The objective of this work was to formulate subcutaneous implants loaded with a model hydrophobic compound, olanzapine (OLZ) using robocasting - a 3D-printing technique. The formulated cylindrical implants were prepared from blends composed of OLZ mixed with either poly(caprolactone) (PCL) or a combination of PCL and poly(ethylene)glycol (PEG). Implants were characterised using scanning electron microscopy (SEM), thermal analysis, infrared spectroscopy, and X-ray diffraction and the crystallinity of OLZ in the formulated devices was confirmed. In vitro release studies demonstrated that all the formulations were capable of maintaining sustained drug release over a period of 200 days, with the maximum percentage drug release observed to be c.a. 60% in the same period.

Made available in DSpace on 2022-04-29T08:35:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-01 Artemether (ART) and lumefantrine (LUM) are the gold standard antimalarial drugs used for the treatment of malaria in children and pregnant women. Typically, ART and LUM are delivered orally in the form of a combined tablet, however, the appropriateness of this route of administration for these drugs is questionable due to the poor absorption and therefore bioavailability observed unless administered alongside lipid-rich foods. Transdermal drug delivery in the form of a patch-type system has been identified as a viable alternative to the conventional tablet-based therapy. A novel, surfactant-based ART-LUM formulation (S3AL), developed for transdermal delivery, may eliminate the shortcomings associated with oral delivery; namely poor drug absorption which is caused by the inherently low solubility of ART and LUM. Moreover, by successfully delivering these antimalarials transdermally, first-pass metabolism will be avoided leading to enhanced drug bioavailability in both cases. The S3AL formulation contained ART and LUM at equal concentrations (2.5% w/w of each) as well as Procetyl® AWS (30% w/w), oleic acid (10% w/w), 1-methyl-2-pyrrolidone (10% w/w), and water (45% w/w). The addition of LUM to the formulation changed the system from a striae structure to a dark field structure when visualized by a polarized light microscope. Additionally, this system possessed higher viscosity and superior skin bioadhesion, as evidenced by mechanical characterization, when compared to a similar formulation containing ART alone. S3AL was also proven to be biocompatible to human keratinocyte cells. Finally, in vitro studies demonstrated the propensity of S3AL for successful delivery via the transdermal route, with 2279 295 µg cm-2 of ART and 94 13 µg cm-2 of LUM having permeated across dermatomed porcine skin after 24 h, highlighting its potential as a new candidate for the treatment of malaria. Graduate School of Bioscience and Technology of Bioactive Products Biology Institute University at Campinas, Sao Paulo School of Pharmacy Queen's University Belfast UNESP- University Estadual Paulista Faculdade de Ciencias Farmaceuticas UNESP, Sao Paulo Faculty of Pharmaceutical Science University at Campinas, Sao Paulo Centre for Information Technology 'Renato Archer' (CTI) 3D Printing Open Lab - Laprint, Sao Paulo Universidade de S o Paulo Departamento de Bot nica Instituto de Biociencias, Sao Paulo Faculdade de Ciencias Médicas Universidade Estadual de Campinas, Sao Paulo School of Mechanical Engineering University of Campinas, Sao Paulo UNESP Univ Estadual Paulista Instituto de Biociencias, Sao Vicente University of Calabar UNESP- University Estadual Paulista Faculdade de Ciencias Farmaceuticas UNESP, Sao Paulo UNESP Univ Estadual Paulista Instituto de Biociencias, Sao Vicente

Despite the existence of a variety of contraceptive products for women, as well as decades of research into the prevention and treatment of human immunodeficiency virus (HIV), there is still a globally unmet need for easily accessible, acceptable, and affordable products to protect women's sexual and reproductive health. Microarray patches (MAPs) are a novel platform being developed for the delivery of hormonal contraception and antiretroviral drugs. MAPs provide enhanced drug delivery to the systemic circulation via the transdermal route when compared to transdermal patches, oral and injectable formulations. These minimally invasive patches can be self-administered by the user, reducing the burden on health care personnel. Since MAPs represent needle-free drug delivery, no sharps waste is generated after application, thereby eliminating possible MAP reuse and risk of needle-stick injuries. This review discusses the administration of contraceptive and antiretroviral drugs using MAPs, their acceptability by end-users, and the future perspective of the field.

Diabetes affects approximately 450 million adults globally. If not effectively managed, chronic hyperglycaemia causes tissue damage that can develop into fibrosis. Fibrosis leads to end-organ complications, failure of organ systems occurs, which can ultimately cause death. One strategy to tackle end-organ complications is to maintain normoglycaemia. Conventionally, insulin is administered subcutaneously. Whilst effective, this delivery route shows several limitations, including pain. The transdermal route is a favourable alternative. Microneedle (MN) arrays are minimally invasive and painless devices that can enhance transdermal drug delivery. Convincing evidence is provided on MN-mediated insulin delivery. MN arrays can also be used as a diagnostic tool and monitor glucose levels. Furthermore, sophisticated MN array-based systems that integrate glucose monitoring and drug delivery into a single device have been designed. Therefore, MN technology has potential to revolutionise diabetes management. This review describes the current applications of MN technology for diabetes management and how these could prevent diabetes induced fibrosis.

The poor aqueous solubility of existing and emerging drugs is a major issue faced by the pharmaceutical industry. Water-miscible organic solvents, termed co-solvents, can be used to enhance the solubility of poorly soluble substances. Typically, drugs with poor aqueous solubility and Log P &gt, 3 are not amenable to delivery across the skin. This study investigated the use of co-solvents as reservoirs to be used in combination with hydrogel-forming microneedles to enhance the transdermal delivery of hydrophobic compounds, namely Nile red, olanzapine and atorvastatin. A custom-made Franz cell apparatus was fabricated to test the suitability of a liquid drug reservoir in combination with polymeric microneedles. A co-solvency approach to reservoir formulation proved effective, with 83.30% &plusmn, 9.38% of Nile red dye, dissolved in 1 mL poly(ethylene glycol) (PEG 400), permeating neonatal porcine skin over 24 h. PEG 400 and propylene glycol were found to be suitable reservoir media for olanzapine and atorvastatin, with approximately 50% of each drug delivered after 24 h. This work provides crucial proof-of-concept evidence that the manipulation of microneedle reservoir properties is an effective method to facilitate microneedle-mediated delivery of hydrophobic compounds.

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.