overview: Oral transmucosal delivery of eletriptan hydrobromide provides rapid and effective relief to migraine sufferers.
sauce: Malmö University
For migraine drugs to be effective, it is important that the active substance is released quickly into the bloodstream. The tablets currently on the market go through the body’s metabolism, making them less effective and delaying relief.
A research team at Malmö University believes that this can be avoided by shortening the mucous membrane in the mouth.
The active substances in migraine drugs are known as triptans. It is a generic name for tryptamine-based drugs that inhibit specific signaling substances in the brain that can react with serotonin receptors and thereby prompt the experience of pain. A signal transmitter that affects sexual behavior, appetite, sleep, pain, and more.
In a research project called Oral Transmucosal Delivery of Eletriptan for Neurological Disorders, Sabrina Valetti and her colleagues explored the use of the least cardiotoxic triptan, eletriptan hydrobromide (EB). selected.
“A regular triptan tablet has to pass through both the stomach and the liver, where most of its metabolism takes place. We investigated the possibility that EB can reach the blood vessels of the mouth directly from the mucous membrane under the tongue,” explains Valetti, who leads the project at the Biofilms Research Center for Biointerfaces.
“We know from patient studies that it is important that the maximum blood concentration of the substance is reached within two hours in order to be effective. We investigated the concentration of 3D human cells and found that the expected concentration was higher in 3D human cells than that provided by regular migraine drugs. Only if the value goes up,” she continues.
“Our bodies have a buffer system that regulates and balances temporary pH fluctuations, and no toxic effects on mucous membranes were seen during the four hours when the pH value increased from 6.8 to 10.4. But I’m not sure if this feels uncomfortable in the mouth.”
The biggest challenge lies in the fact that the mucosa is a relatively thick tissue and a barrier that protects us from various external attacks. A detailed study was conducted to examine this specific barrier effect in detail.
Results are expected in the spring.
About this migraine and neuropharmacology research news
author: press office
sauce: Malmö University
contact: Press Office – Malmö University
image: image is public domain
Original research: open access.
“Oral Transmucosal Delivery of Eletriptan for Neurological Disorders” by Sabrina Valetti et al. International Journal of Pharmaceuticals
overview
Oral transmucosal delivery of eletriptan for neurological disorders
Migraine is a highly prevalent neurological disorder that affects approximately one billion people worldwide and significantly reduces quality of life. As a self-medication practice, oral triptan administration is the most common option despite the relatively late treatment initiation and low bioavailability of the drug.
To overcome these problems, here we present the first study on the potential for oral transmucosal delivery of eletriptan hydrobromide (EB), one of the safest triptans to our knowledge. to introduce.
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Based on a comprehensive series of in vitro and ex vivo experiments, we highlight the conditions necessary for oral transmucosal delivery, which may result in drug plasma concentrations comparable to or greater than conventional oral administration.
From histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs mucosal barrier integrity after 4 h of exposure.
At the cellular level, EB is taken up by human oral keratinocytes within the first 5 minutes without inducing toxicity at concentrations relevant for transmucosal delivery. Given the pKa Since EB is within the physiological range, we systematically investigated the effect of pH on both solubility and transmucosal permeability.
As the pH increased from 6.8 to 10.4, drug solubility decreased significantly from 14.7 to 0.07 mg/mL. At pH 6.8, EB yielded the highest drug flux and total permeation across the mucosa, whereas at pH 10.4, EB exhibits a larger permeation coefficient and thus a higher ratio of permeated drug to applied drug. Permeation experiments using model membranes confirmed the pH-dependent permeation profile of EB.
The distribution of EBs in different cellular compartments of keratinocytes is pH dependent. Briefly, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and phospholipid headgroups. Furthermore, we demonstrate that the chemical permeation enhancer DMSO can be used to significantly enhance drug permeation (i.e., 12- to 36-fold increase).
Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical research for rapid and safe treatment of migraine.
