Lozenges used for Sublingual Absorption
Sublingual, meaning literally 'under the tongue' refers to a method of administering substances via the mouth in
such a way that the substances are rapidly absorbed via the blood vessels under the tongue rather than via the
digestive tract. The route of absorption via the highly vascularised buccal mucosa allow the substances a more
direct access to the blood circulation, thus providing direct systemic administration.
Medically, sublingual drug administration is applied in the field of cardiovascular drugs, hormones, steroids,
some barbiturates and enzymes. It has been a developing field in the administration of many vitamins and minerals
that are found to be readily and thoroughly absorbed by this method. Sublingually absorbed nutrition, which avoids
exposure to the gastric system and liver, means direct nutritional benefits.
There is considerable evidence that most sublingual substances are absorbed by simple diffusion; the sublingual
areas acting rather like a sponge, readily soaking up the substances. However, not all substances are permeable
and accessible to the buccal mucosa. The mucosa functions primarily as a barrier - similar to skin. But while it
was once believed that the barrier of human skin was 'impenetrable' it is now recognized that the dermis is a good
site for the absorption of many substances (e.g., vitamins E & C creams; hormones; nicotine patches) and it
is a growing field of endeavor. Similarly the buccal mucosa presents an ideal site for absorption. This potential
continues to be explored for the administration of many drugs - providing many useful studies and a better understanding
of the modus operandi - although the benefits of the less intrusive nutrition therapies have had little opportunity
as yet to be as thoroughly researched.
The Mechanics of Sublingual Absorption
The absorption potential of the buccal mucosa is influenced by the lipid solubility and therefore the permeability
of the solution (osmosis); the ionization (pH); and the molecular weight of the substances. For example, absorption
of some drugs via the buccal mucosa is shown to increase when carrier pH is lower (more acidic) and decreases with
a raising of pH (more alkaline).
The cells of the oral epithelium and epidermis are also capable of absorbing by endocytosis (the uptake of particles
by a cell as if by hollowly wrapping itself around it. These engulfed particles are usually too large to diffuse
through its wall). It is unlikely that this mechanism is used across the entire stratified epithelium. It is also
unlikely that active transport processes operate within the oral mucosa. However, it is believed that acidic stimulation
of the salivary glands, with the accompanying vasodilatation, facilitates absorption and uptake into the circulatory
system.
The mouth is lined with a mucous membrane that is covered with squamous epithelium and contains mucous glands.
The buccal mucosa is similar to the sublingual mucosal tissue.
The salivary glands consist of lobules of cells that secrete saliva through the salivary ducts into the mouth.
The three pairs of salivary glands are the parotid, the submandibular and the sublingual that lies on the floor
of the mouth. The more acid the taste, the greater the stimulation of salivary output; serving also to avoid potential
harm to acid-sensitive tooth enamel by bathing the mouth in copious neutralizing fluid. With stimulation of salivary
secretion oxygen is consumed and vasodilator substances are produced; and the glandular blood flow increases, due
to increased glandular metabolism.
The sublingual artery travels forward to the sublingual gland, it supplies the gland and branches to the neighboring
muscles and to the mucous membranes of the mouth, tongue and gums. Two symmetrical branches travel behind the jawbone
under the tongue to meet and join at its tip. Another branch meets and anastomoses with the submental branches
of the facial artery. The sublingual artery stems from the lingual artery - the body's main blood supply to the
tongue and the floor of the mouth - which arises from the external carotid artery. The proximity with the internal
carotid artery allows fast access to its route supplying the greater part of the cerebral hemisphere.
The importance of water
Water is physiologically the most important component of the body; it is the medium in which all of the physiological
activities necessary for life take place. The properties of water greatly influence the digestion and absorption
of lipids. Water molecules strongly attract each other because of the asymmetrical distribution of electrons within
each molecule; the area of the oxygen atom has many electrons and hydrogen atoms have few electrons. Water is the
major component of both the interior of the cell and the extra cellular fluid that surrounds the cell. A little
over half the body water is inside cells. About 15 - 20% of the extra cellular water is in the plasma. The remainder
is held in the extra vascular, extra cellular and interstitial fluid.
Osmosis
In order for a nutrient to be effectively absorbed sublingually, it needs to be able to travel across the buccal
mucous membranes; by a process of diffusion known as osmosis which applies to all forms of absorption by the body;
governing both intestinal and sublingual absorption. The distribution of water across cell walls depends on the
osmotic difference in the blood between the intracellular and extra cellular fluid. The distribution of water across
blood vessel walls is determined by the in-vivo osmotic pressure of plasma and the total outward hydrostatic pressure.
Unlike the cell membrane, the capillary wall is freely and rapidly permeable to small molecules. The diffusion
of water across a membrane that is only permeable to water depends on the molecular weight of the particle. Small
particles that readily dissolve in water, rarely present a problem in permeation and diffusion, and so are able
to move freely between the tissues of the body. Active transportation into cells leads to rapid metabolisation
of the substances. Molecules such as glucose (fructose) and amino acids are essential for cell metabolism and special
mechanisms have evolved to facilitate their rapid diffusion and permeation across cell membranes.
Sublingual Nutrition
The advantages of sublingually administering nutrients seem to be manifold, offering improved bioavailability and
more rapid metabolisation of the nutrients which are absorbed more fully. It allows individual control over the
dosage for optimum benefit, within safe guidelines, and can allow absorption in a palatable and easily administered
form, regardless of gastro-intestinal difficulties. It is especially useful for those who experience difficulty
in swallowing tablets. Sublingual nutrients are available in lozenges, or in fine powders, which are held under
the tongue or in the mouth, until dissolved. Water-soluble vitamins are passively absorbed, by osmosis, and the
vitamin molecules are massed in the micelles for transport across the mucosal membranes.
References
1 Squier CA, Johnson NW. Brit Med Bull, 31: 169 (1975).
2 Garibaldi M Kanig JL. Oral ther. Pharmacol, 1.440 (1965)
3 Vogt D, Trenk D, Jahnchen E, Phar-maco kinetic., Abt. fur Klin. Pharmak, Herz-Zentrum, Germany.
4 Bogeart MG, Clinical Pharmaco kinetics of Nitrates, University of Gent Medical School, Belgium.
5 Fort S, Lewis M, Luscombe D, John D Prelim. investig. of efficacy sublingual verapamil. 1994; 37: 460-3
Bibliography
1. Gray's Anatomy.
2. Florence AT Attwood D. Physiochemical Principles of Pharmacy.
3. Zilva JF Pannall PR. Clinical Chemisty in Diagnosis and Treatment.
4. Sinclair D, An introduction to functional anatomy.
5. Raynor J, Anatomy and physiology.
6. British National Formulary.
7. Harison RJ, Textbook of medicine
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