1. Absorption at different routes of administration
Dr. Jwan Mohammed

2. Oral route Parenteral route Transdermal route Rectal route
Intravenous
Intramuscular
Subcutaneous
Transdermal route
Rectal route
Pulmonary route

3. Oral route of administration
The oral route of administration is the most convenient route for drug administration because of low production cost, better suitability for self administration, higher level of patient safety and better patient compliance
The drug must be soluble in the GI fluids, withstand acidic and enzymatic degradation, and have ability to permeate intesinal mucosa
Drugs that are absorbed will inter the portal vein to reach the liver where it could be metabolized before it could reach the systemic circulation, this is called the first pass effect
First pass effect can reduce the bioavailability of drugs

4. Parenteral drug administration
Parenteral preparation are administered to the patient by injection
The medicine may be injected into the vascular system, muscle or soft tissue to provide systemic action, or into an anatomical space such as a joint or into a particular organ to provide local action
Medicines administered by injection because the drug substance may not be absorbed orally, or because a rapid effect is required like in emergencies , or the patient is unconscious, or a prolonged controlled effect is required

5. Factors affecting absorption from the injection site
The movement of drug from the site of administration to the blood circulation is drug absorption
There is no drug absorption for drugs injected Intravenously into the blood stream or into the fluid of distribution like cerebrospinal fluid, or directly into the site of action like intra-articular or intraocular.
In contrast, drugs administered intramuscularly, subcutaneously or intradermally must undergo absorption to reach the systemic circulation.

6. Both the subcutaneous and the intramuscular area are richly supplied with blood capillaries.
Lymph vessels are found extensively in the subcutaneous tissue and in connective tissue sheathes around muscles, but the muscular tissue contain only a small number of lymphatic vessels.
Subcutaneous and intramuscular injections may be either solutions or suspensions.

7. When aqueous solutions of drugs are administered by subcutaneous or intramuscular injection drug absorption is comparable to that seen with oral administration and absorption is complete within 30 minutes
The lipid solubility of the drug can play a role and delay the absorption of a drug in the subcutaneous fatty tissue.
Vasoconstriction at the site of injection can delay the absorption of the drug and prolong the retention of the drug at site of injection.
This is used to prolong the action of local anesthetic using adrenalin as a vasoconstrictor.

8. Large molecules like proteins and peptides (e. g
Large molecules like proteins and peptides (e.g. insulin) and colloidal particles (e.g. injectable iron complexes) with molecular weights larger than 20 KDa are absorbed by lymph vessels.
Large molecules are better absorbed in the subcutaneous area but not well absorbed in the intramuscular area.

9. Implants
Implants are placed subcutaneously to obtain sustained drug delivery.
The mechanism of drug delivery are drug diffusion, polymer dissolution or a combination of both
Implants based on a non-biodegradable polymer such as polydimethylsioxane, deliver drugs by simple diffusion at a rate dependent on drug solubility in the polymer and surface area of implant
Implants based on biodegradable polymer like poly lactic acid deliver drug by diffusion and/or polymer erosion
The drug release rate is directly proportional to the physical dimentions of the implant

10. Transdermal delivery
Using the skin for drug delivery can be advantageous because of avoiding first pass effect.
Topical application of drug can treat local disorders , the drug is retained within the skin
Transdermal delivery uses the skin to deliver drug to the systemic circulation.
The skin is a complex multilayer organ but the outermost layer (the stratum corneum) provides the main barrier to drug delivery

11. Drugs suitable for topical and transdermal delivery usually have
molecular weight less than 500 Da
log P (partition coefficient) between 1 and 4
effective daily dose of less than 10 mg /day
The drug transport through the skin is mainly by passive diffusion.
Topical drug delivery formulations are common such as cream, gel, lotions and ointments
Patch is used for transdermal delivery.

12. Drug transport through the skin
Initially drug molecules should be delivered from the formulation. If the drug is present in the solid form it should be dissolved and diffused from the formulation.
If the formulation contain dissolved drug then molecules that are nearest to the skin surface inters the skin and replaced by other molecules diffused from within the formulation.
Once the drug is at the outer layer of the stratum corneum there are three pathways for the drug to cross the skin to the systemic circulation.

13. Pathways of drug absorption through the skin
1. the appendages or shunt pathway (short cut):
In this the drug molecules are passing across the stratum corneum barrier through sweat glands and hair follicles associated with sebaceous gland
The largest appendages is the hair follicles and associated sebaceous gland
The drug first partition into the sebum or sweat and then diffuse out from the gland into the epiderms

14. This provide a fast drug absorption compared to the time required for the drug to pass through the intact stratum corneum.
The fractional area occupied by these glands are relatively small, e.g. on the forearm hair follicles occupy approximately 0.1% of the surface area while on the forehead this may be as much as 13%
The shunt route is important for electrical enhancement of transdermal drug delivery (iontophoresis) and for early time course for passive drug delivery the skin, where diffusion through the intact stratum corneum has yet not reached steady state.

15. 2. intracellular (transcellular) pathway:
Drug passes through the intact stratum corneum (brick wall) through the cells.
First the drug partition into and diffusing through the keratin filled corneocyte which is an aqueous environment.
Then partitioning from the corneocyte into the intercellular lipid domain and diffusing through the lipoidal tissue then again partitioning into another keratin filled corneocyte until reaching the epiderm

16. 3. Intracellular pathway:
in this route the drug molecules partition into the lipid bilayers between the cells and then diffuse through a tortuous (twisting) route within the continuous lipid domain.
All drugs will use all the three routes to pass through, but the proportion of molecule crossing by the different routes will vary depending on the physicochemical properties of the permeant.

18. Then the molecules should diffuse through the epidermal layer to reach the epidermal-dermal junction where it passes through the capillaries to the systemic circulation.
During transport the drug molecule (permeant) may bind to skin components like keratin or may be metabolized by the esterases, peptidases and hydrolases that are present in the skin
that can reduce the bioavailability of topically applied drugs, for example, only around 70% of topically applied glyceryl trinitrate (nitroglycerin) may be bioavailable.

19. Rectal route of drug administration
Rectal drug delivery can be used to provide local or systemic effect.
Local action is desired for the local treatment of pain and itching, mostly due to the occurrence of haemorrhoids.
Locally active drugs include astringents, antiseptics, local anaesthetics, vasoconstrictors, anti-infammatory compounds and soothing and protective agents. Some laxatives also fall into this category
All drugs which are orally administered can be given by this route to provide systemic action. Antiasthmatic, anti-inflammatory and analgesic drugs are widely administered by the rectal route.

20. Absorption of drugs from the rectum
Absorption of drug from the rectum is primarily by passive diffusion.
The rate and extent of drug absorption is lower than the oral route, mainly due to the small surface area or absorption.
drug molecules from the rectum can enter the general circulation either directly or by passing through the portal vein and liver leading to first pass metabolism.
Drug absorbed in the middle and lower part of the rectum will pass directly to the general circulation and avoid first-pass metabolism in the liver while the upper part will pass into the portal vein and is prone to first pass metabolism.

21. Depending on the character of its vehicle a suppository will either dissolve in the rectal fluid or melt on the mucous layer.
Since the volume of rectal fluid is so small, dissolution of the complete vehicle will be difficult and requires extra water. Due to osmotic effects (of the dissolving vehicle) water is attracted, with a resultant unpleasant sensation for the patient.
Dissolved drug molecules will have to diffuse through the mucous layer and then into and through the epithelium forming the rectal wall.
The process of absorption will be by passive diffusion

22. Advantages of rectal administration
Safe and painless means of administration and removal of the dosage Drugs liable to degradation in the gastrointestinal tract can be administered
Hepatic first-pass elimination of high clearance drugs is partially a voided
Small and large doses can be administered
The duration of drug action can be controlled by using a suitable formulation

23. 5. Suitable for the long-term care of elderly and terminally ill patients
6. It is a useful way to administer medication to children who are unwilling or unable to tolerate the drug by the oral route
7. Administration of rectal suppositories, tablets or capsules is a simple procedure
8. It is useful for patients who are nauseous or vomiting

24. Limitations of rectal route of administration
Patient acceptability and compliance is poor, especially for long- term therapy
Up ward movement of the dosage form from the local site can increase first-pass metabolism
Suppositories can leak
Insertion of suppositories may be problematic
Generally, drug absorption from suppositories is slow compared to oral or intravenous ad ministration

25. Pulmonary drug delivery
Pulmonary delivery may be used for drugs having local or systemic activity
The administration of a drug at its site of action can result in a rapid onset of activity, e.g. bronchodilating drugs for the treatment of asthma.
smaller doses can be administered locally compared to delivery by the oral or parenteral routes, thereby reducing the potential incidence of adverse systemic effects and reducing drug costs.
The pulmonary route is also useful where a drug is poorly absorbed or rapidly metabolized when administered orally

26. The avoidance of first-pass metabolism in the liver may also be advantageous, although the lung itself has some metabolic capability.
The lung may also be used as a rout e for delivering drugs having systemic activity, because of its large surface area, the abundance of capillaries and the thinness of the air–blood barrier.
This has been used in the treatment of migraine with ergotamine by inhaler, and is a potential for delivering biopharmaceuticals, such as insulin, vaccines and growth hormone

27. To deliver a drug into the airways, it must be presented as an aerosol
an aerosol is defined as a two phase system of solid particles or liquid droplets dispersed in air or other gaseous phase (propellant)
The deposition of a drug/aerosol in the airways is dependent on four factors:
1. the physicochemical properties of the drug,
2. the formulation,
3. the delivery device,
4. the patient (breathing patterns and clinical status)

28. The efficacy of a therapeutic aerosol is dependent on its stability to penetrate the respiratory tract and be deposited.
To penetrate to the peripheral (respiratory) regions, aerosols require a size less than about 5 or 6 µm, with less than 2 µm being preferable for alveolar deposition
Larger particles or droplet s are deposited in the upper respiratory tract and are rapidly removed from the lung by the mucociliary clearance process and swallowed.
Insoluble particles penetrating to the alveolar regions, and which are not solubilized in situ, are removed more slowly by macrophages

29. Hydrophobic compounds are usually absorbed at a rate dependent on their oil/water partition coefcients, whereas hydrophilic materials are poorly absorbed through membrane pores at rates inversely proportional to molecular size
the airways’ membrane is preferably permeable to the unionized form of a drug.
Some drugs, such as sodium cromoglicate, are partly absorbed by a active transport mechanism, whilst large macromolecules may be absorbed by transcytosis.

30. The rate of drug absorption, and consequently drug action, can be influenced by the formulation.
Rapid drug action can generally be achieved using solutions or powders of aqueous soluble salts,
whereas slower or prolonged absorption may be achieved using suspension formulations, powders of less soluble salts or novel drug delivery systems such as liposomes and microspheres.