SUBLINGUAL

GROUP 3
BALUMA, Cirlene Bless

CANTILADO, Christea A.

DECIERDO, Widell C.

OCIO, Jean Margarette Z.

SABATE, Mary Blessa M.

ANATOMY OF THE SUBLINGUAL GLAND
Sublingual glands are also known as the
salivary glands which are present in the
floor of mouth underneath the tongue.
Because of the secretions of the glands,
the interior area of the mouth is kept
lubricated, which is necessary for chewing
and swallowing food. The lubrication and
binding functions of the sublingual glands
cannot be underestimated. Low levels of
saliva production can make the process of
swallowing much more difficult and will
increase the potential for food to lodge in
the throat. Along with providing
lubrication, these glands also aid in the
promotion of good oral hygiene.

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. There is considerable
evidence that most sublingual substances are absorbed by simple diffusion; the sublingual
area acting rather likes litmus paper, readily soaking up the substances. However, not all
substances are permeable and accessible to oral mucosa.

MOUTH

 Lined with mucous membrane covered with squamous epithelium

 Contains mucous glands TONGUE
 Muscular organ in the mouth that manipulates mastication
 Sensitive and kept moist by saliva
 Richly supplied with nerves and blood vessels

SALIVARY GLANDS

 consist of lobules of cells which secrete saliva through the salivary duct into the
mouth
 produce mucin
 Providing lubricant and aid in the promotion of good oral hygiene

3 Pairs of Salivary Glands

 Parotid Gland
 Submandibular Gland
 Sublingual Gland

LINGUAL ARTERY

 Body’s main blood supply to the tongue and the floor of the mouth
SUBLINGUAL ARTERY

 travels toward the sublingual gland

 Supplies the gland and branches to the neighboring muscles and to the mucous
membranes of mouth, tongue and gums.

LINGUAL FRENULUM

 a fold of mucous membrane

 secures the tongue to the floor for the mouth
 limits tongue's posterior movement

PHYSICAL MAKE UP OR CHARACTERISTICS

 Sublingual area is more permeable than buccal (cheek) area

 Produce mucin & help promote production of saliva

 Absorption is directly proportional to membrane thickness 100-200 nm

 Rapid onset of action

 Rich in blood supply

 Improved bioavailability

FACTORS AFFECTING DRUGS ABSORPTION VIA SUBLINGUAL ROUTE

Lipophilicity of drug:

For a drug to be absorbed completely through sublingual route, the drug must have
slightly higher lipid solubility than that required for GI absorption is necessary for
passive permeation.

Solubility in salivary secretion:

In addition to high lipid solubility, the drug should be soluble in aqueous buccal fluids
i.e. Biphasic solubility of drug is necessary for absorption.

pH and pKa of the saliva:

As the mean pH of the saliva is 6.0, this pH favors the absorption of drugs which remain
unionized. Also, theabsorption of the drugs through the oral mucosa occurs if the pKa is
greater than 2 for an acid and less than 10 for a base.

Binding to oral mucosa:

Systemic availability of drugs that bind to oral mucosa is poor.

Thickness of oral epithelium:

As the thickness of sublingual epithelium is 100‐200 μm which is less as compared

to buccal thickness. So the absorption of drugs is faster due to thinner epithelium
and also the immersion of drug in smaller volume of saliva.
Oil to water partition coefficient:

Compounds with favorable oil‐ to‐water partition coefficients are readily absorbed through
the oral mucosa. An oil‐water partition coefficient range of 40‐2000 is considered
optimal for the drugs to be absorbed sublingually.

REQUIREMENTS FOR DRUG ABSORPTION

 Osmosis

In order for a drug 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 extracellular fluid. 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.

 No bitter taste
 Dose lowers than 20mg, e.g. nifedipine
 Small to moderate molecular weight
 Good stability in water and saliva
 Partially non ionized at the oral cavities pH
 Undergoing first pass effect e.g. ketotifen fumarate

TYPES OF DRUGS THAT COME IN A SUBLINGUAL FORM INCLUDE:

• cardiovascular drugs (nitroglycerin, verapamil)

• steroids

• barbiturates

• vitamins

• some medications for mental health conditions

COMMON DRUGS USED SUBLINGUALLY
• Recently many drugs have been formulated for sublingual drug delivery with an
objective of rapid drug release and restricting the region of drug release to
mouth. Compared to commonly used tablets, capsules and other oral dosage
forms, sublingual absorption is generally much faster and more efficient.
• Sublingual dosages are convenient for young children, the elderly and patients
with swallowing difficulties, and in situations where potable liquids are not
available. Peak blood levels of most products administered sublingually are
achieved within 10‐15 minutes, which is generally much faster than when those
same drugs are ingested orally.
• Sublingual absorption is efficient. The percent of each dose absorbed is generally
higher than that achieved by means of oral ingestion. Various types of sublingual
dosage forms are available in market like tablets, films and sprays.

DRUGS USED IN THE FORMULATION OF SUBLINGUAL DOSAGE FORMS

DRUGS CATEGORY DOSAGE FORM

Physostigmine salicylate Anti-Alzheimer’s Tablet

Scopolamine Opioid analgesic Spray

Captopril Anti-hypertensive Tablet

Amlodipine Anti-hypertensive Tablet

Furosemide Diuretic Tablet

Nitroglycerine Anti-anginal Tablet

Terbutaline sulphate Bronchodilator Tablet

Ondansetron Anti-emetic Film

Hydrochloride
Salbutamol sulphate Anti-asthmatic Film
 SOME MARKETED SUBLINGUAL TABLETS

BRAND NAME DRUG CATEGORY

Subutex Buprenorphine Opioid Analgesic

Avitan Lorazepam Antianxiety

Edular Zolpidem tartrate Sedatives/Hypnotics

Isordil Isosorbide dinitrate Vasodilators

Saphris Asenapine Antipsychotic agent

Prohealth Melatonin Hormone

melatonin
Nitrostat Nitroglycerine Antianginal
Temgesic Buprenorphine Opioid Analgesic

DISEASE: DYSPHAGIA
Dysphagia is the medical term for the
symptom of difficulty in swallowing. People
with dysphagia are sometimes unaware of
having it. It is a sensation that suggests
difficulty in the passage of solids or liquids
from the mouth to the stomach, a lack of
pharyngeal sensation, or various other
inadequacies of the swallowing
mechanism. Dysphagia is distinguished
from other symptoms
including odynophagia, which is defined as
painful swallowing and globus, which is the
sensation of a lump in the throat. A person
can have dysphagia without odynophagia (dysfunction without pain), odynophagia without
dysphagia (pain without dysfunction), or both together.

Xerostomia is a common side effect of a large numer of commonly used drugs. Dysphagia
due to xerostomia can be caused by two general mechanisms. First, the dryness of the
mouth can lead to impaired oropharyngeal bolus transport, giving the patient the feeling or
impaired swallowing. This form of dysphagia is usually easy to detect by taking a careful
clinical history. Second, a causal link between xerostomia as a valid indicator of salivary
gland hypofunction and esophagitis has been suggested.
Classification

• Oropharyngeal dysphagia - arises from abnormalities of muscles, nerves or

structures of the oral cavity, pharynx, and upper esophageal sphincter.

• Esophageal dysphagia - where the underlying cause arises from the body of the
esophagus, lower esophageal sphincter, or cardia of the stomach, usually due to
mechanical causes or motility problems.

DYSPHAGIA: FACTORS AFFECTING DRUG ABSORTION VIA SUBLINGUAL

ROUTE
 Stasis of a drug prolongs esophageal drug-transit time, thereby affecting
pharmacokinetics and decreasing effectiveness
 For capsules or tablets, delayed transit may lead to premature drug-release,
which reduces bioavailability and drug degradation
 In extended release dosage forms, stasis may cause delayed plasma peak
concentrations of the drug.
 Drugs can cause esophageal injury through various pathophysiological
mechanisms
 The relatively large size of the tablets or adherent surface of the drug
increase the risk of retention in the esophagus, especially in esophageal
dysphagia.

DYSPHAGIA: TREATMENT
Treating dysphagia depends on the type and severity of a patient's swallowing difficulty. For
difficulties in the mouth and throat areas, treatments are generally focused on swallowing
therapy, including exercises, and dietary changes. For problems in the esophagus, treatment
options may include surgery or medicine. Feeding tubes are also options for treating
dysphagia, including nasogastric or endoscopic tubes.

References:

Sublingual Mucosa As A Route For Systemic Drug Delivery

International Journal of Pharmacy and Pharmaceutical Sciences Vol 3, Suppl 2, 2011

http://www.ijppsjournal.com/Vol3Suppl2/1092.pdf

http://www.tandfonline.com/doi/full/10.1517/17425247.2016.1142971

https://en.wikipedia.org/wiki/Dysphagia