LTS Lohmann Therapie-Systeme (Germany)

Ketamine is administered predominantly via the intravenous route for the various indications, including anesthesia, pain relief and treatment of depression. Here we report on the pharmacokinetics of sublingual and buccal fast-dissolving oral-thin-films that contain 50 mg of S-ketamine in a population of healthy male and female volunteers. Twenty volunteers received one or two oral thin films on separate occasions in a randomized crossover design. The oral thin films were placed sublingually (n = 15) or buccally (n = 5) and left to dissolve for 10 min in the mouth during which the subjects were not allowed to swallow. For 6 subsequent hours, pharmacokinetic blood samples were obtained after which 20 mg S-ketamine was infused intravenously and blood sampling continued for another 2-hours. A population pharmacokinetic analysis was performed in NONMEM pharmacokinetic model of S-ketamine and its metabolites S-norketamine and S-hydroxynorketamine; p < 0.01 were considered significant. S-ketamine bioavailability was 26 ± 1% (estimate ± standard error of the estimate) with a 20% lower bioavailability of the 100 mg oral thin film relative to the 50 mg film, although this difference did not reach the level of significance. Due to the large first pass-effect, 80% of S-ketamine was metabolized into S-norketamine leading to high plasma levels of S-norketamine following the oral thin film application with 56% of S-ketamine finally metabolized into S-hydroxynorketamine. No differences in pharmacokinetics were observed for the sublingual and buccal administration routes. The S-ketamine oral thin film is a safe and practical alternative to intravenous S-ketamine administration that results in relatively high plasma levels of S-ketamine and its two metabolites.

Being the largest and most accessible organ, the skin is an attractive target for drug delivery. However, the efficient barrier function of the stratum corneum presents a considerable challenge to the delivery of therapeutic into and across the skin. Nevertheless, years of research in the area of skin permeation culminated with the regulatory approval of the first transdermal patch for the delivery of the antiemetic drug scopolamine in 1979. Since then, the delivery of therapeutics across the skin has progressed considerably with the development of various innovative drug delivery strategies, with microneedles being one of them. Since the first microneedle patent was filed in the 1950s, microneedle research has gained considerable momentum. Microneedle-based delivery strategy offers a minimally invasive drug delivery approach while obviating first-pass hepatic metabolism. Judicious selection in formulation designs coupled with advancement in the microfabrication techniques have led to the development of novel microneedle systems. The first part of this chapter aims to provide a general outline of the anatomy of the skin along with strategies that have been explored in delivering drugs into and across the skin. The second part of this chapter covers the development, classification, and manufacturing methods of manufacture microneedles along with a discussion with regards to commercialising such technology.

Cyclodextrinliganden: Kohlenhydrate eignen sich als Gerüstmoleküle mit einem Muster aus metallbindenden Sauerstoffatomen. Die zweiwertigen Formen der biologisch wichtigen Metalle Eisen und Mangan können Teil solcher Assoziate sein (siehe Struktur; blau Fe, rot O, grün Gegenion, gelb H-Brücken zwischen Wassermolekülen). Die Assoziate werden durch günstige Beiträge, die nicht aus der Kohlenhydrat-Metall-Wechselwirkung resultieren, stabilisiert.