Routes of drug administration may be either applied locally or administered systemically. It depends on nature of drug as well as patient. Factors, which govern the choice of routes of drug administration of a drug, are:
- Physical and chemical nature of the drug.
- Rate and extent of absorption of the drug from different routes.
- Site of drug action.
- Desired onset of action.
- Condition of the patient.
- Effect of digestive juices and first pass metabolism.
Local Routes of drug administration
These routes of drug administration are used for localized lesion. The advantages are:
- Attainment of high concentration at the desired site.
- No or minimal systemic side effects.
The local routes of drug administration are:
1. Skin: Drug may be applied on skin as ointment, dressings, cream, lotion, powder, paste, etc.
2. Mucous membranes: The dosage form depends on the site.
- Anal canal: As ointment, suppositories.
- Bronchi and lungs: As aerosols (nebulized solution or fine powder) inhalations.
- Eyes, ear and nose: As drops, ointment, irrigation, nasal spray.
- Gastrointestinal tract: As non-absorbable drugs given orally, e.g. kaolin, neomycin, aluminum hydroxide, etc.
- Mouth and pharynx: As paints, lozenges, mouthwashes, gargle.
- Urethra: As jelly, irrigation solution.
- Vagina: As cream, douches, pessaries, vaginal tablets, powders.
3. Arterial supply: This route can be used to infuse anticancer drugs through femoral or brachial artery for limb malignancies; for contrast in angiography.
4. Deeper tissues: Certain drugs can be administered by using syringe and needle to reach deeper tissue provided their systemic absorption is slow, e.g.
a. Intra-arterial injection.
b. Intrathecal injection.
c. Retrobulbar injection.
Systemic routes of drug administration
Through systemic routes, drug is absorbed into blood. It is then distributed all over including the site of action through circulation.
Oral ingestion of a drug is the oldest and commonest routes of drug administration. Both solid and liquid dosage forms can be given orally.
Advantages of this type of routes of drug administration
- Often painless
- Does not need assistance
- Need not be sterile
Limitations of this type of routes of drug administration
- Onset of action is slow.
- May cause nausea and vomiting.
- Irritant and unpalatable drugs cannot be administered by this route.
- Cannot be used for uncooperative, unconscious, and vomiting patient.
- Certain drugs are destroyed by digestive juices (penicillin) or irk liver (nitro-glycerine, testosterone, lidocaine, etc.).
- Certain drugs are not absorbed (streptomycin).
- Absorption of certain drugs is irregular and unpredictable.
Precautions in this type of routes of drug administration
- In order to enhance the passage into stomach and permit rapid dissolution, the capsules and tablets should be washed down with a glass of water with the patient in upright posture (sitting or standing).
- To avoid damage to the esophageal mucosa, do not give drugs orally to a recumbent patient. The damage can be caused by drugs like tetracyclines, iron salts, and slow release potassium salts.
Sometimes pills and tablets are coated as under:
i. They are coated by sugars, gums, synthetic resins, polyhydric alcohols, waxes, coloring agents and flavoring agents to make them more palatable and acceptable.
ii. They are coated with gluten, cellulose acetate phthalate and anionic co-polymers of methacrylic acid and its esters. These substances do not permit the acid juice of the stomach to disintegrate them but permit disintegration in the intestinal alkaline juice. So the purpose of enteric coating is:
a. To get desired concentration of the drug in the small intestine.
b. To retard the absorption of the drug.
However, there are certain disadvantages of this type of routes of drug administration, that is of enteric coating such as:
- Difficulty to maintain uniform body drug concentration.
- Required to administer large quantities of the drug to achieve a therapeutic concentration at the site of action.
- May cause more adverse actions.
- Necessity for frequent dosing and poor patient compliance.
Timsules/spansules: These are sustained release or time release preparations. They release the active drug over an extended period of time. To achieve this goal, the particles of the drug are covered with coatings which dissolve at different time intervals in order to provide uniform medication over a prolonged period. The basis for the so called controlled release, extended release, sustained release or prolonged action pharmaceutical preparation (oral dosage form) is dependent on its rate of dissolution in gastrointestinal tract fluids. Potential advantages of such preparations in routes of drug administration are:
- Reduction in the frequency of administration of the drug.
- Improved patients’ compliance.
- Maintenance of therapeutic effect overnight.
- Decreased incidence and/or intensity of undesirable effects by elimination of the peaks in drug concentration.
However, such products have some drawbacks in routes of drug administration:
- During repeated drug administration, trough drug concentration resulting from controlled release dosage form may not be different from those observed with immediate-release preparations, although time interval between trough concentrations is greater for a well designed controlled release preparation.
- It is possible that dosage form may fail.
- “Dose-dumping” with resultant toxicity can occur, since the total dose of drug ingested at one time may be several times the amount present in the conventional preparation.
Controlled release preparations are most appropriate for drugs with short half-life (less than 4 hours).
The tablet or pellet containing the drug is placed under the tongue or crushed in the mouth in order to spread it over the buccal mucosa. Only lipid soluble and non-irritating drugs can be administered by this route in routes of drug administration.
- Relatively rapid absorption.
- Quick onset of action.
- Drug can be spitted after the desired effect.
- Liver is bypassed; so drugs with high first pass metabolism can be absorbed directly into systemic circulation.
Drugs given sublingually are nitroglycerine, clonidine, isoprenaline, nifedipine, methyl testosterone and buprenorphine.
In routes of drug administration,Many drugs maybe absorbed readily through the mucous membrane of the nose. Examples are posterior pituitary powder, applied as a snuff; and spray of nebulized solutions.
In routes of drug administration,For systemic effect, drugs can be put into rectum. They are used as suppository or retention enema. Examples are aminophylline, diazepam, indomethacin, etc.
- Certain irritant and unpleasant drugs can be given by this route in routes of drug administration.
- This route can be used in presence of recurrent vomiting.
- Inconvenient and embarrassing.
- Absorption is slow, irregular and often unpredictable.
- Irritant drug may cause inflammation.
Gases and volatile liquids are given by inhalation, e.g. general anesthetics, amyl nitrite.
- Rapid absorption
- Controlled administration is possible
- Quick elimination
Irritant vapors can cause:
- Inflammation of respiratory tract
- Increased secretion
Drugs with high lipid solubility can be applied over the skin for slow and prolonged absorption after being incorporated in an ointment or impregnated in adhesive patches or strips. Examples are nitroglycerine, hyoscine, etc. Advantage is that liver is bypassed.
When a drug is administered by routes of drug administration other than the gastrointestinal tract, it is called parenteral route.
- Onset of action is faster and sure.
- Accuracy of dose is ensured.
- No gastric irritation and vomiting.
- Can be used in unconscious, uncooperative or vomiting patients.
- No interference by food or digestive juices.
- Irritant drugs to stomach can be given.
- Drugs which are not absorbed in the small intestine can be administered.
- Liver is by passed.
- Can be employed in case of diarrhea and in patients unable to swallow.
- Self-medication is difficult and often needs assistance.
- Less safe and more risky.
- Preparation has to be sterilized.
- Technique is invasive and painful.
- Local tissue injury is possible.
- Danger of infection, if proper care is not taken.
Important parenteral routes of drug administration are:
Subcutaneous (s.c.): Drug is deposited in the loose subcutaneous tissue. Self-injection is possible because deep penetration is not needed. The commonest drug used by this routes of drug administration is insulin. Repository (depot) preparation (oil solution or aqueous suspension) can be injected for prolonged action.
- Absorption is slow because this tissue is richly supplied by nerves but is less vascular.
- Irritant drugs cannot be injected.
- This routes of drug administration should be avoided in patients of shock because the absorption is undependable.
Some special forms of this routes of drug administration are:
a. Hypodermoclysis: This procedure is used in pediatric practice to inject large quantity of saline subcutaneously. Drug absorption from the subcutaneous area can be enhanced by the addition of the enzyme hyaluronidase.
b. Pellet implantation: To provide sustained release of drug, solid pellet of the drug is introduced by a trochar and cannula, e.g. DOCA, testosterone.
c. Dermojet: A high velocity jet of drug solution is projected from a microfine orifice using a gun-like implement. Procedure is painless and suited for mass inoculation.
d. Sialistic (non-biodegradable) and biodegradable implant in routes of drug administration: Crystalline drug is packed in tubes made of suitable materials. It is implanted under the skin. Slow and uniform release of the drug occurs over months to provide constant blood levels. The non-biodegradable implants have to be removed later on but not the biodegradable ones. This has been tried for hormones and contraceptives.
Intramuscular (i.m.): The drug is injected in one of the large skeletal muscles such as deltoid, triceps, gluteus maximus, and rectus femoris. Volume of injection should not exceed 10 ml.
- Mild irritants, suspensions and colloids can be injected.
- Absorption is faster so onset of action is rapid.
- Less painful.
- Avoid injection near a nerve because an irritant solution can damage the nerve and cause severe pain and even paresis of the muscles supplied by it.
- Do not give i.m. injection into the buttock until the child starts to walk, because at this stage gluteus maximus is very tiny. So the lateral side of the thigh should be used in younger children.
Intravenous (i.v.): The drug is given in one of the superficial veins. It can be given intravenously: (a) as a bolous injection, e.g. frusemide, (b) over 5—10 minutes, e.g. aminophylline, (c) in an infusion which is 50—100 ml or more in volume.
Indications of infusion are:
- To slow the administration of the drug, e.g. morphine
- To maintain a constant plasma level of the drug, e.g. dopamine
- To administer large volumes either rapidly or over prolonged periods of time, e.g. fluids in dehydration or shock.
- Onset of action is quick.
- Highly irritant drugs can be given.
- Smaller dose is required.
- Large volume can be infused.
- Response is accurately measurable, so titration of the dose with the response is possible.
- Suspension cannot be injected.
- Thrombophlebitis of the injected vein may occur.
- Necrosis of adjacent tissue may develop if extravasation of irritant drug occurs.
- Hazardous route as vital organs are exposed to high concentration.
- Ensure that needle is in the vein and then inject the drug.
- Inject minimum quantity of the drug to produce a particular effect.
- With certain drugs (iron, aminophylline, pentothal, calcium), in routes of drug administration injection is to be given slowly as sudden high blood concentration may be dangerous.
- Irritant solutions should be administered by piggybacking into a running intravenous drip or through a central line intravenous site which should be reselected at regular intervals, if irritating solutions are given through a peripheral vein.
- On extravasation of irritating fluid, it should be aspirated through the cannula before removing it.
Intradermal injection; The drug is injected into the skin raising a bleb (e.g. BCG vaccine, sensitivity test) or scarring (multiple puncture of the epidermis through a drop of drug (smallpox vaccination) is done. This routes of drug administration is employed for specific purpose only.
8. New Drug Delivery Systems
Various novel drug delivery systems have been developed in routes of drug administration.
1. Drugs are incorporated in a programmed dosage form. They administer the medicament at a predetermined rate over an extended period of time from a single application.
i. Ocusert: It is placed directly under the eyelid. It can deliver a steady amount of pilocarpine round the clock for seven days. It does not cause any discomfort. It obviates the need of repeated application of eyedrops.
ii. Progestasert: It is an intrauterine contraceptive device. It causes controlled release of minute quantities of progesterone within the uterus for a year.
2. Prodrug: It is an inactive chemical derivative. After administration, it is converted into the pharmacologically active drug by biotransformation. The advantages of the use of prodrugs are:
- It overcomes the barriers which limit the usefulness of a drug in routes of drug administration. Examples are propoxyphene, napsylate, chloramphenicol palmitate, L-dopa, talampicillin.
- Maybe used to achieve longer duration of action, e.g. esters of phenothiazines and penicillin.
- May be used in routes of drug administration to provide site specific delivery of drugs such as methenamine which is converted to formaldehyde and ammonia at the acidic urinary pH. It is used as a urinary antiseptic.
3. For continuous or intermittent (pulsed) administration of drugs, computerized, miniature syringe pumps have been developed. They are now being used for optimal drug effect of insulin and GnRH (gonadotropin releasing hormone).
4. Monoclonal antibodies: In routes of drug administration, It is now possible to grow very large numbers of antibody producing cells from a single B cell. This is done by fusing a B cell to a myeloma cancer cell. The resulting hybridoma retains 2 main features from its 2 parent cells. It could grow indefinitely like the cancer cell yet also produce and secrete antibodies like the B cell. The antibodies produced by this technique are called monoclonal antibodies (MAbs) because they are derived from a single hybrid cell. Now monoclonal antibodies against cancer cell antigens have been developed for ‘targeted” delivery of anticancer drugs. These antibodies ‘home in’ on the cancer cells. Thus they deliver lethal concentration of the drug selectively to the cancer tissue.
5. Packing in liposomes: Liposomes are minute vesicles of certain phospholipids in aqueous suspension. Non-lipid soluble drugs may be filled in these vesicles. This is routes of drug administration of specific target orientated drug delivery system. Intravenous route is commonly used for the administration of liposomes.
Liposomes have been utilized to administer:
- Anticancer drugs, e.g. daunorubicin and doxorubicin
- Antibiotic such as gentamicin
- Antifungal drug like amphotericin-B
[Source: Principles of Pharmacology for Dental Students]