Regulatory status of N-alkylamide containing health products.

N-alkylamides (NAAs) are secondary metabolites occurring in more than 25 plant families. Plants containing NAAs are traditionally used in food for flavouring, tingling, pungent and saliva-enhancing properties but also to treat various diseases. NAA containing products are abundantly available on the market as food, cosmetics, medical devices and medicinal products.

-alkylamide profiling of and extracts by liquid and gas chromatography-mass spectrometry.

and are both plants belonging to the Asteracea family and are traditionally used for their medicinal properties. It has already been shown that some -alkylamides (NAAs) are responsible for these pharmacological actions. Therefore, in the present study, the NAA content of the two plants was analytically characterised.

Fish Hydrolysates: A Regulatory Perspective of Bioactive Peptides.

For the first time introduced on the Japanese market, bioactive fish hydrolysates are now available all over the world as food supplements, functional food ingredients or nutricosmeceuticals. They are generally produced from low value fish waste, an almost inexhaustible source of raw material, and are sold as high value products, making them economically interesting from a manufacturer's view point. Most of these products have health or structure/function claims on their packages with different actions like antihypertensive, blood-glucose lowering, anxiolytic, and skin anti-aging activities.

Quantitative In Vitro and In Vivo Evaluation of Intestinal and Blood-Brain Barrier Transport Kinetics of the Plant N-Alkylamide Pellitorine.

Objective. To evaluate the gut mucosa and blood-brain barrier (BBB) pharmacokinetic permeability properties of the plant N-alkylamide pellitorine. Methods.

Blood-brain barrier transport kinetics of the cyclic depsipeptide mycotoxins beauvericin and enniatins.

The cyclic depsipeptide mycotoxins beauvericin and enniatins are capable of reaching the systemic circulation through various routes of exposure and are hence capable of exerting central nervous system (CNS) effects, if they are able to pass the blood-brain barrier (BBB), which was the main objective of this study. Quantification of the mycotoxins was performed using an in-house developed and validated bio-analytical UHPLC-MS/MS method. Prior to the BBB experiments, the metabolic stability of the mycotoxins was evaluated in vitro in mouse serum and brain homogenate.

Mucosal and blood-brain barrier transport kinetics of the plant N-alkylamide spilanthol using in vitro and in vivo models.

Background: N-alkylamides (NAAs) are a large group of secondary metabolites occurring in more than 25 plant families which are often used in traditional medicine. A prominent active NAA is spilanthol. The general goal was to quantitatively investigate the gut mucosa and blood-brain barrier (BBB) permeability pharmacokinetic properties of spilanthol.

Regulatory development of geriatric medicines: To GIP or not to GIP?

Geriatric patients represent the main users of medicines, but are historically often minimally included in clinical trials, resulting in a gap in the knowledge of the benefit/risk balance of medicines in this heterogeneous population. As the worldwide population is aging, the need for safe and effective medicines for older patients is proportionally increasing. The aim of this review is to provide an overview of the current regulatory status of the development of geriatric medicines, the encountered challenges and the view of the involved stakeholders, coming to the conclusion whether it is necessary or not to implement a Geriatric Investigation Plan (GIP), by analogy with pediatrics.

Gas chromatographic method for the determination of lumefantrine in antimalarial finished pharmaceutical products.

A simple method has been developed and validated for quantitative determination of lumefantrine in antimalarial finished pharmaceutical products using gas chromatography coupled to flame ionization detector. Lumefantrine was silylated with N,O-bis(trimethyl-silyl)trifluoro-acetamide at 70°C for 30 minutes, and chromatographic separation was conducted on a fused silica capillary (HP-5, 30 m length × 0.32 mm i.

Implementation of a single quad MS detector in high-throughput transdermal research of plant extracts.

In this study, a new type of single quadrupole mass spectrometric detector was implemented in transdermal research. The local skin pharmacokinetic properties of the plant N-alkylamides (NAAs) pellitorine and anacycline, present in an Anacyclus pyrethrum extract, and spilanthol, present in a Spilanthes acmella extract were investigated. This single quad MS detection method showed great advantages compared to the traditional UV detector.

Enniatin-containing solutions for oromucosal use: Quality-by-design ex-vivo transmucosal risk assessment of composition variability.

Fusafungine, a mixture of the cyclic hexadepsipeptides enniatins, is currently on the market for the treatment of upper respiratory tract diseases because of its bacteriostatic and anti-inflammatory effects. In this study, a quality-by-design risk assessment was performed with two objectives: (i) investigate whether enniatins are able to permeate the mucosa and reach blood circulation, as the summary of product characteristics indicates this is not the case, and if so, to quantify their transmucosal kinetics and (ii) study the influence of excipient concentration variability on mucosal permeation. First, the concentration of the two main excipients isopropyl myristate and ethanol, known penetration enhancers, in several marketed samples was determined using GC-FID.

Human skin permeation of emerging mycotoxins (beauvericin and enniatins).

Currently, dermal exposure data of cyclic depsipeptide mycotoxins are completely absent. There is a lack of understanding about the local skin and systemic kinetics and effects, despite their widespread skin contact and intrinsic hazard. Therefore, we provide a quantitative characterisation of their dermal kinetics.

The influence of the acyl chain on the transdermal penetration-enhancing effect of synthetic phytoceramides.

Background/aims: The skin has become very attractive as a route for drug administration. Optimization of topical drug formulations by the addition of penetration enhancers may facilitate the passage of drugs through the stratum corneum.

Methods: In this paper, the skin penetration effect of phytosphingosine and 9 derived phytoceramides (PCERs) on 3 transdermal model drugs (i.

Quantitative transdermal behavior of pellitorine from Anacyclus pyrethrum extract.

The plant Anacyclus pyrethrum (AP) consists of several N-alkylamides with pellitorine as main constituent. AP extracts are known to be biologically active and some products for topical administration containing AP plant extracts are already commercially available with functional cosmeceutical claims. However, no transdermal data for pellitorine are currently available.

Risk evaluation of impurities in topical excipients: The acetol case.

Pharmaceutical excipients for topical use may contain impurities, which are often neglected from a toxicity qualification viewpoint. The possible impurities in the most frequently used topical excipients were evaluated for their toxicity hazard. Acetol, an impurity likely present in different topical pharmaceutical excipients such as propylene glycol and glycerol, was withheld for the evaluation of its health risk after dermal exposure.

UHPLC-MS/MS method for the determination of the cyclic depsipeptide mycotoxins beauvericin and enniatins in in vitro transdermal experiments.

Currently, dermal exposure data of cyclic depsipeptide mycotoxins beauvericin and enniatins are completely absent with a lack of local skin and systemic kinetics, despite their widespread skin contact and intrinsic hazard. Therefore a sensitive and specific bioanalytical high-throughput UHPLC-MS/MS method was developed for the quantitative and simultaneous determination of cyclic depsipeptide mycotoxins beauvericin and enniatins (A, A1, B, B1, D, E, C/F) in human skin Franz diffusion cell samples. The limits of detection ranged between 10 and 17pg/ml, while the total run time was only 4.

A critical quality parameter in quantitative fused-core chromatography: The injection volume.

As part of the method development, the injection volume as a critical quality attribute in fast fused-core chromatography was evaluated. Spilanthol, a pharmaceutically interesting -alkylamide currently under investigation in our laboratory, was chosen as the model compound. Spilanthol was dissolved in both PBS and MeOH/HO (70/30, v/v) and subsequently analyzed using a fused-core system hereby selecting five chromatographic characteristics (retention time, area, height, theoretical plates and symmetry factor) as responses.

Skin penetration enhancing properties of the plant N-alkylamide spilanthol.

Ethnopharmacological Relevance: Plants are often used for skin diseases in different ethnopharmacological systems. Local and systemic effects of topically applied compounds can be significantly increased by plant constituents having skin penetration enhancers.

Materials And Methods: In this study, we examined the proposed penetration enhancing properties of spilanthol, an N-alkylamide abundantly present in several Asteraceae plants like Spilanthes acmella L.

Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides.

Ethnopharmacological Relevance: N-Alkylamides (NAAs) are a promising group of bioactive compounds, which are anticipated to act as important lead compounds for plant protection and biocidal products, functional food, cosmeceuticals and drugs in the next decennia. These molecules, currently found in more than 25 plant families and with a wide structural diversity, exert a variety of biological-pharmacological effects and are of high ethnopharmacological importance. However, information is scattered in literature, with different, often unstandardized, pharmacological methodologies being used.