Summary: Using oral transmucosal delivery of eletriptan hydrobromide provides faster and more effective relief for migraine sufferers.

Source: Malmö University

For migraine medicine to be effective, it is very important that the active ingredient gets into the bloodstream immediately. The pills that are currently on the market go through the body’s metabolism, which means that they are less effective and there is a delay in getting relief.

A research team at the University of Malmö believe they can achieve this by using a shortcut on the mucous membrane in the mouth.

The active ingredients in migraine medications are known as triptans. This is a generic name for tryptamine-based drugs that react with serotonin receptors and block certain signals in the brain that can cause pain. Serotonin is one of the most important neurotransmitters in the human nervous system and affects sexual behavior, appetite, sleep and pain among other things.

In the research project Oral Transmucosal Delivery of Eletriptan for Neurological Diseases, Sabrina Vatti and her research colleagues chose to work with Eletriptan hydrobromide (EB), a triptan with less cardiotoxicity.

“Typical triptan pills have to pass through the stomach and liver, where a significant part of the metabolism occurs. Studies show that more than half of the triptan dose is broken down on the way before it reaches the blood. Vatti, who leads the project at the Biofilms Research Center for Biointerfaces, directly into the oral vein through the mucosa under the tongue. We investigated the possibility of penetration.

This shows the brain
Serotonin is one of the most important neurotransmitters in the human nervous system and affects sexual behavior, appetite, sleep and pain among other things. The image is in the public domain.

“We know that in patient studies it is necessary to reach a high concentration in the blood within two hours for the substance to have an effect. So we investigated what the expected concentration of EB is after this time with our method. We saw that the expected concentration in 3D human cells is higher than that given by standard migraine pills. This “It was also the case with pig mucus, but only if the pH was raised,” she said.

“Our body has a buffer that regulates and balances temporary pH variations, and we didn’t see any toxic effects on the mucosa when the pH value increased from 6.8 to 10.4 over a period of four hours. But what we don’t know is whether this is unpleasant in the mouth or not.”

The biggest challenge is that the mucous membrane is a relatively thick tissue and a barrier that should protect us from various external attacks. Last fall, to gain a better understanding of this particular barrier effect, they conducted experiments in which they examined in detail the amount of lipids believed to play a critical role in the membrane of pig’s nose.

The result is expected in the spring.

So Migraine and Neuropharmacology Research News

Author: Press office
Source: Malmö University
Contact: Press Office – Malmö University
Image: The image is in the public domain.

Preliminary study: Open Access.
Oral transmembrane delivery of eletriptan for neurological disorders” by Sabrina Vatti et al International Pharmaceutical Journal


Oral transmembrane delivery of eletriptan for neurological disorders

Migraine is a highly prevalent neurological disorder that affects approximately 1 billion patients worldwide with severe debilitating symptoms that significantly reduce quality of life. As a practice of self-medication, oral administration of triptans is the most common option despite relatively slow onset of action and low drug bioavailability.

To address these issues, we present the first study of possible oral transmucosal delivery of eletriptan hydrobromide (EB), one of the safest triptans, to our knowledge.

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This shows the brain

Based on comprehensive in vitro and ex vivo experiments, we demonstrate the conditions required for oral transmucosal delivery, which results in drug plasma concentrations similar to or even higher than those expected from conventional oral administration.

Through histological and tissue integrity studies, we conclude that EB does not induce morphological changes or impair mucosal barrier integrity after 4 h of exposure.

At the cellular level, EB was internalized in human oral keratinocytes within the first 5 min of transmucosal delivery without toxicity at relevant concentrations. Considering pKA EB falls within the physiological range, we systematically investigated the effect of pH on both solubility and transmucosal permeation.

When the pH increases from 6.8 to 10.4, the drug solubility decreases significantly from 14.7 to 0.07 mg/ml. At pH 6.8, EB showed the highest drug flux and overall concentration in the mucosa, while at pH 10.4 EB showed greater permeability and the ratio of contaminant to applied drug was high. Permeation tests with model membranes showed that EBP

The distribution of EB in different cellular compartments of keratinocytes depends on the pH. Briefly, high drug ionization leads to high binding to the cell membrane, indicating ionic interactions between EB and phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to significantly improve drug permeation (i.e., 12- to 36-fold enhancement).

Taken together, this study provides important findings on the transmucosal delivery of eletriptan through the oral cavity and paves the way for clinical trials for rapid and safe treatment of migraine.

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