Exploring Opportunities in Transmucosal Drug Administration: A Comprehensive Approach

By Roberto Gabach - Director & New Projects Manager


Many companies, once focused solely on developing transdermal patches, are now also venturing into transmucosal forms, such as oral films.


A closer look at transmucosal routes:


While the oral route remains the most widely used method of drug administration in human medicine, it can present challenges related to absorption and irritation. In several cases, these challenges can be overcome by parenteral routes, including transdermal and transmucosal pathways.


The intranasal route is a parenteral drug administration pathway categorized under transmucosal, along with buccal and rectal routes. The rectal route gained significance in our country in the ’60s when various products were presented in suppositories, with acetaminophen (paracetamol) standing out for pediatric fever control.


Both nasal and buccal routes (including sublingual) offer more predictable drug absorption compared to the rectal route, and many medications are currently being used or are under development through these pathways. Within the oral cavity, three areas are utilized for transmucosal drug passage: beneath the tongue (sublingual), between the upper molar gum and cheek (buccal), and between the incisor mucosa and upper lip (gingival). Among these, sublingual drug absorption is the highest, while gingival absorption is the lowest.


The nasal mucosa is a significant drug administration route, with a growing number of available and developing products. The intranasal route enhances systemic bioavailability for certain drugs by bypassing the first-pass hepatic effect. Additionally, some drugs may reach the central nervous system (CNS) via the nasal route, bypassing the blood-brain barrier. This access, known as “nose-to-brain” in English, allows drugs to reach the brain through the communication provided by the cribriform plate of the ethmoid bone, where vessels and nerves pass.


Advantages of intranasal drug administration include:


Non-invasive and painless

Easy administration

Favorable tolerance profile

Rapid absorption and onset of action

Absence of first-pass metabolism

Better bioavailability than the oral route for small molecules

Potential to enhance bioavailability using permeation enhancers

Limitations of intranasal drug administration include:


Limited by the relatively small absorption area

Limited potential to slow absorption time

Drug absorption may be affected by local nasal conditions

Absorption enhancers and surfactants may affect nasal mucosa

Nasal irritation may occur

Various strategies are employed to increase intranasal drug absorption, including the use of surfactants, bioadhesive agents, and agents with vasoactive properties. Certain surfactants have demonstrated the ability to increase nasal transmucosal absorption, even for large peptides and proteins. Vasoactive agents, on the other hand, increase local blood flow in the nasal mucosa, thereby enhancing drug diffusion into the bloodstream.


The first FDA-approved drugs with systemic activity via the nasal route were desmopressin, lipressin (currently discontinued), and intranasal oxytocin (currently discontinued). According to the Orange Book, all these products were approved before 1982.


Nasal formulations can take the form of sprays, drops, gels, suspensions, emulsions, liposomal and micellar forms, and microparticles. Compared to liquid nasal formulations, nasal gels are administered as a low-viscosity solution. Upon contact with the nasal mucosa, the polymer in the gel undergoes a conformational change, forming a gel.


Regarding the action of drugs administered nasally, they can have either local or systemic effects.


Conclusions and Reflections:


This brief analysis of nasal drug administration aimed to highlight its therapeutic potential and the pivotal role it may play in the future. With a continued commitment to excellence and innovation, Amarin is exploring the development of new drug administration forms, demonstrating its ability to adapt to an environment where science and technology are constantly evolving, providing effective and advanced solutions to emerging medical needs.

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