L33 - Absorption via Different Routes of Drug Delivery

What does enteral mean?

Within or by way of the intestine

• Oral

• Rectal

What does parenteral mean?

Located outside the alimentary canal, taken into the body or administered in a manner other than through the digestive tract

• Injections and influsions

• Implantable devices

Advantages of Intravenous Drug Delivery

• Rapid (almost an immediate effect)

• Dose (precise dosing, large volumes possible)

• 100% of the dose reaches systemic circulation

DIsadvantages of Intravenous Drug Delivery

• Potential toxicity - rapid Cp elevation (can be controlled by infusion)

• Suitable vein

• Professional required - administration and monitoring

• Cost

• Duration (infusion can extend dosing)

What is intramuscular drug delivery?

• Rich capillary bed

• Passive diffusion of drug

• Blood flow is important (there’s more blood flow in the deltoid than in the buttock, therefore there is more rapid uptake in the deltoid)

• Carrier solvent absorption

Advantages of Intramuscular Drug Delivery

• Relatively large volume

• Sustained release

Disadvantages of Intramuscular Drug Delivery

• Professional required

• Erratic absorption - exercise increases blood flow, so blood flow would increase drug uptake

What is subcutaneous drug delivery?

Passive diffusion into capillaries or lymphatics (peptides)

Advantages of Subcutaneous Drug Delivery

• Slow, sustained delivery

• Self administration possible

• Implants for long term delivery

Disadvantages of Subcutaneous Drug Delivery

• Small doses

• Pain and irritation from repeated injections

“Other” routes for drug delivery

Most surfaces in the body have an epithelial lining of one or more cell layers. 1 layer = simple epithelium

More than 1 layer = stratified epithelium

What is nasal drug delivery for?

Topical delivery for treatment of allergy, congestion, and infection

Why don’t we want the oral route for systemic delivery?

• Avoidance of first pass metabolism

• Drugs sensitive to intestinal metabolism

• Acid sensitive drugs like peptides

• Polar compounds with poor oral absorption

What is the main function of the nose?

When inhaling cold dry air, the temperature can go to within 10C of the body temp

It also increases the humidity, and filters the air going into the lungs

How does the nose-to-brain drug delivery work?

• Olfactory epithelium

Is the ocular drug delivery route possible to deliver drugs to the systemic circulation?

No

Ocular drug delivery

• Drugs administered solely for treatment of local conditions, not a viable route for systemic delivery

Corneal structure & Absorption routes

Corneal route = The major route for ocular drug absorption, either by transcellular (lipophilic) or paracellular (hydrophilic) diffusion

Conjunctival route = Drug passes through the conjunctiva and sclera, however, most drug will be lost into the local capillary bed and enter the systemic circulation

Why is delivering drug to the eye kinda useless?

A lot of the drug is lost

Drug dose goes into the eye, and most of it will go into the tear gland which will then be swallowed, but like some will going into systemic circulation and a tiny bit will go into the ocular tissue

Vaginal Drug Delivery

• Topically effective for local treatment

• Interest now lies in delivery for systemic effects via mucosal absorption (avoiding hepatic first pass)

• The vaginal drug delivery route can hold 2-3m fluid

• Normal pH varies between 4 and 5

• Epithelium thickness will be different at different times of the month and post vs pre menopausal women

Pulmonary Drug Delivery

• Primarily for treating respiratory conditions like asthma

• Reduces dose needed if given via other routes (side effects)

• Drugs delivered by nebulizers, dry powder inhalers, and metered dose inhalers

• Lungs oxygenate blood, so huge potential for systemic delivery

Alveoli

A rich capillary bed surrounding alveoli and so the drug can go into systemic circulation

Transcellular pathway in the pulmonary epithelia and absorption

Passive diffusion of small lipophilic drugs through the epithelium, down a concentration gradient. No firm evidence of significant transporters for drug uptake.

Transdermal drug administration

• The skin is a barrier (50M water inside, much less outside)

• Usually this route has drugs applied as creams to treat local conditions

• Avoids hepatic first pass metabolism, and also conditions that degrade the drug in the stomach or the GI tract