Routes of drug administration.

1. 2/23/2018
DIPTO KUMER SARKER
1
1
Routes of drug administration
Routes can be divided into two parts:
1. Local route
2. Synthetic route
Local route:
1. Topical:
Drugs can be efficiently delivered to the localized lesions on skin, oropharyngeal/ nasal mucosa,
eyes, ear canal, anal canal or vagina in the form of lotion, ointment, cream, powder, rinse, paints,
drops, spray, lozengens, suppositories or pesseries.
Some of these are given below:
a) Mouth and pharynx: as a paint, gargle, lozenges, mouth wash etc.
b) Eye, ear and nose: irrigation , spray.
c) Gastrointestinal tract: non absorbable drugs given orally.
d) Bronchi and lungs: inhaler (aerosol).
e) Urethra – jelly, irrigating sol.
f) Vagina – tablet, insert , cream , powders, and douches.
g) Anal canal –ointments.
Nonabsorbable drugs given
 Orally For action on g.i. mucosa (sucralfate, vancomycin)
 Inhalation of drugs for action on bronchi (salbutamol, cromolyn sodium) and
 Irrigating solutions/jellys (povidone iodine, lidocaine) applied to urethra are other forms of
topical medication.

2. 2/23/2018
DIPTO KUMER SARKER
2
2
2. Deeper tissue:
Certain deep areas can be approached by using a syringe and needle, but the drug should be in
such a form that systemic absorption is slow
Example:
A. intra-articular injection (hydrocortisone acetate in knee joint),
B. infiltration around a nerve or intrathecal injection (lidocaine),
C. retrobulbar injection (hydrocortisone acetate behind the eyeball).
3. Arterial supply:
This route can be used to infuse anticancer drugs through femoral or brachial artery for limb
malignancies; for contrast in angiography.
 Systemic route:
I. Oral route :
Advantages:
 Safe
 More convenient
 Does not need any assistance
 Noninvasive
 Painless
 The medicament does not need to be sterile
 Both solid and liquid doses form
 Solid( powders, capsules, tablets, spansules, dragess, moulded tablets, gastrointestinal
therapeutic systems)
 Liquid( syrups, emulsions, mixtures)
Disadvantages/ limitations of oral route of administration:
 Action of drugs is slower and thus not suitable for emergencies.
 Unpalatable drugs (chloramphenicol) are difficult to administer; drug may be filled in
capsules to circumvent this.
 May cause nausea and vomiting (emetine).
 Cannot be used for uncooperative/unconscious/ vomiting patient.

3. 2/23/2018
DIPTO KUMER SARKER
3
3
 Absorption of drugs may be variable and erratic; certain drugs are not absorbed
(streptomycin).
 Certain drugs are destroyed by digestive juices (penicillin G, insulin) or in liver (GTN,
testosterone, lidocaine).
II. Sublingual :
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.
Advantages
 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.
Disadvantages:
 Unpalatable & bitter drugs are difficult to administer.
 Irritation of oral mucosa can be occur.
 Drugs are not given in large quantities.
 Few drugs are absorbed in this case.
Example: Nitroglycerine, clonidine, isoprenaline, nifedipine, methyl testosterone and
buprenorphine.
III. Rectal :
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.
Advantages:
 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.

4. 2/23/2018
DIPTO KUMER SARKER
4
4
Disadvantages:
 Inconvenient and embarrassing.
 Absorption is slow, irregular and often unpredictable.
 Irritant drug may cause inflammation.
 Drug absorbed into external haemorrhoidal veins (about 50%) bypasses liver, but not that
absorbed into internal haemorrhoidal veins.
Example: Diazepam, indomethacin, paracetamol, ergotamine.
IV. Cutaneous:
Highly lipid soluble drugs can be applied over the skin for slow and prolonged absorption. The
liver is also bypassed.
The drug can be incorporated in an ointment and applied over specified area of skin.
Absorption of the drug can be enhanced by rubbing the preparation, by using an oily base and by
an occlusive dressing.
 Transdermal therapeutic systems (TTS):
These are devices in the form of adhesive patches of various shapes and sizes (5–20 cm2
) which
deliver the contained drug at a constant rate into systemic circulation via the stratum corneum.
The drug (in solution or bound to a polymer) is held in a reservoir between an occlusive backing
film and a rate controlling micropore membrane, the under surface of which is smeared( spread
something across or over a surface) with an adhesive impregnated( saturated) with priming(layer
of base paint) dose of the drug. The adhesive layer is protected by another film that is to be peeled
off just before application.
The drug is delivered at the skin surface by diffusion for percutaneous absorption into circulation.
The micropore membrane is such that rate of drug delivery to skin surface is less than the slowest
rate of absorption from the skin.

5. 2/23/2018
DIPTO KUMER SARKER
5
5
This offsets any variation in the rate of absorption according to the properties of different sites. As
such, the drug is delivered at a constant and predictable rate irrespective of site of application.
Usually chest, abdomen, upper arm, lower back, buttock or mastoid region are utilized.
Drugs: Transdermal patches of GTN, fentanyl, nicotine and estradiol
For different drugs, TTS have been designed to last for 1–3 days.
Advantages:
 Though more expensive, they provide smooth plasma concentrations of the drug without
fluctuations; minimize interindividual variations and side effects>
 Drug is subjected to little first pass metabolism.
 They are also more convenient many patients prefer transdermal patches to oral tablets of the
same drug; patient compliance is better.
Disadvantages:
 Local irritation and erythema occurs in some cases.
V. Inhalation:
Advantages:
 Volatile liquids and gases are given by inhalation for systemic action, e.g. general anaesthetics.
 Absorption takes place from the vast surface of alveoli—action is very rapid.
 When administration is discontinued the drug diffuses back and is rapidly eliminated in expired
air.
 Thus, controlled administration is possible with moment to moment adjustment.
Disadvantages:
 Irritant vapors (ether) cause inflammation of respiratory tract and increase secretion.

6. 2/23/2018
DIPTO KUMER SARKER
6
6
VI. Nasal:
Advantages:
 The mucous membrane of the nose can readily absorb many drugs.
 Digestive juices and liver are bypassed.
Disadvantages:
 However, only certain drugs like GnRH agonists (Gonadotropin-releasing hormone agonist)
and desmopressin applied as a spray or nebulized solution have been used by this route.
Parenteral route:
(Par—beyond, enteral—intestinal)
Parenteral refers to administration by injection, which takes the drug directly into the tissue fluid
or blood without having to cross the enteral mucosa.
Advantages:
 Drug action is faster and surer (valuable in emergencies).
 Gastric irritation and vomiting are not provoked.
 Parenteral routes can be employed even in unconscious, uncooperative or vomiting patient.
 There are no chances of interference by food or digestive juices.
 Liver is bypassed.
Disadvantages:
 The preparation has to be sterilized and is costlier.
 The technique is invasive and painful, assistance of another person is mostly needed (though
self injection is possible, e.g. insulin by diabetics).
 There are chances of local tissue injury and, in general, parenteral route is more risky than oral.

7. 2/23/2018
DIPTO KUMER SARKER
7
7
Important parenteral route:
1. Subcutaneous:
The drug is deposited in the loose subcutaneous tissue which is richly supplied by nerves.
Advantages:
 Absorption is slow, so action is prolonged.
 Self injection possible because deep penetration is not needed.
 Repository (depot) preparations that are aqueous suspensions can be injected for prolonged
action.
Disadvantages:
 absorption is slower than intramuscular.
 Only small volumes can be injected.
 This route should be avoided in shock patients who are vasoconstricted— absorption will
be delayed.
Some special forms of this route:
a) Dermojet: In this method needle is not used; a high velocity jet of drug solution is projected
from a microfine orifice using a gun like implement. The solution passes through the
superficial layers and gets deposited in the subcutaneous tissue. It is essentially painless
and suited for mass inoculations.
b) Pellet implantation: The drug in the form of a solid pellet is introduced with a trochar and
cannula. This provides sustained release of the drug over weeks and months, e.g. DOCA,
testosterone.
c) Sialistic (nonbiodegradable) and biodegradable implants: Crystalline drug is packed in
tubes or capsules made of suitable materials and implanted under the skin. Slow and
uniform leaching of the drug occurs over months providing constant blood levels. The non
biodegradable implant has to be removed later on but not the biodegradable one. This has
been tried for hormones and contraceptives (e.g. NORPLANT).

8. 2/23/2018
DIPTO KUMER SARKER
8
8
2. Intramuscular:
The drug is injected in one of the large skeletal muscles—deltoid, triceps, gluteus maximus, rectus
femoris, etc.
Advantages:
 Muscle is less richly supplied with sensory nerves so mild irritants can be injected
 Because of more vascular absorption of drugs in aqueous solution is faster.
 It is less painful.
 Oily solutions, aqueous suspensions can be injected by this route.
 Rapid onset of action.
 First pass avoided.
 Gastric factors can be avoided.
Disadvantages:
 Only up to 10ml drug given
 Local pain and abscess
 Expensive
 Infection
 Nerve damage
 self injection is often impracticable because deep penetration is needed.
 Intramuscular injections should be avoided in anticoagulant treated patients, because it can
produce local haematoma.
 Irritating
3. Intravenous:
The drug is injected as a bolus or infused slowly over hours in one of the superficial veins. The
drug is reaches directly into the blood steam.
Advantages:

9. 2/23/2018
DIPTO KUMER SARKER
9
9
 Rapid onset of action
 The intima of veins is insensitive and drug gets diluted with blood, as a result highly irritant
drugs can be injected.
 The dose of the drug required is smallest (bioavailability is 100%) and even large volumes
can be infused.
 One big advantage with this route is—in case response is accurately measurable (e.g. BP)
and the drug short acting (e.g. sodium nitroprusside), titration of the dose with the response
is possible.
Disadvantages:
 Thrombophlebitis of the injected vein and necrosis of adjoining tissues if extravasation
occurs.
 Only aqueous solutions (not suspensions, because drug particles can cause embolism) are
to be injected intravenously.
 There are no depot preparations for this route.
 Chances of causing air embolism is another risk.
 This is the most risky route—vital organs like heart, brain, etc. get exposed to high
concentrations of the drug.
 There are no emergency route.
4. Intradermal injection:
The drug is injected into the skin raising a bleb (e.g. BCG vaccine, sensitivity testing) or
scarring/multiple puncture of the epidermis through a drop of the drug is done. This route is
employed for specific purposes only.

10. 2/23/2018
DIPTO KUMER SARKER
10
10

11. 2/23/2018
DIPTO KUMER SARKER
11
11
Pharmacokinetics:
Pharmacokinetics is the quantitative study of drug movement in, through and out of the body.
Response is directly proportional to the drug concentration.
Pharmacokinetic considerations, therefore, determine
 the route(s) of administration,
 dose,
 latency of onset,
 time of peak action,
 duration of action
 frequency of administration of a drug.
Biological membrane:
This is a bilayer of phospholipid and cholesterol molecule. Thickness: About 100 A0
.
The polar groups (glyceryl phosphate attached to ethanolamine/choline or hydroxyl group of
cholesterol) and the nonpolar hydrocarbon chains are embedded in the matrix to form a continuous
sheet.
Extrinsic and intrinsic protein molecules are adsorbed on the lipid bilayer. Glycoproteins or glycolipids
are formed on the surface by attachment to polymeric sugars, aminosugars or sialic acids.
The proteins are able to freely float through the membrane: associate and organize or vice versa.
Some of the intrinsic ones, which extend through the full thickness of the membrane, surround fine
aqueous pores. Paracellular spaces or channels also exist between certain epithelial/endothelial cells.
Other adsorbed proteins have enzymatic, carrier, receptor or signal transduction properties.
Drugs are transported across the membranes by:
(a) Passive diffusion and filtration
(b) Specialized transport
a) Passive diffusion
The drug diffuses across the membrane in the direction of its concentration gradient.
The membrane playing no active role in the process.
Drugs are foreign substances (xenobiotics), and specialized mechanisms are developed by the body
primarily for normal metabolites.
Lipid soluble drugs diffuse by dissolving in the lipoidal matrix of the membrane.
The rate of transport being proportional to the lipid : water partition coefficient of the drug.

12. 2/23/2018
DIPTO KUMER SARKER
12
12
A more lipid-soluble drug attains higher concentration in the membrane and diffuses quickly.
Also, greater the difference in the concentration of the drug on the two sides of the membrane, faster is
its diffusion.
Influence of pH
: see KD. Tripathi. Page(11)
Implications of this consideration:
1) Acidic drugs, e.g. aspirin (pKa 3.5) are largely unionized at acid gastric pH and are absorbed from
stomach, while bases, e.g. atropine (pKa 10) are largely ionized and are absorbed only when they
reach the intestines.
2) The unionized form of acidic drugs which crosses the surface membrane of gastric mucosal cell,
reverts to the ionized form within the cell (pH 7.0) and then only slowly passes to the extracellular
fluid. This is called ion trapping,
3) Basic drugs attain higher concentration intracellularly (pH 7.0 vs 7.4 of plasma).
4) Acidic drugs are ionized more in alkaline urine—do not back diffuse in the kidney tubules and are
excreted faster. Accordingly, basic drugs are excreted faster if urine is acidified.
Filtration:
Passage of drugs through aqueous pore in the membrane or through para cellular spaces. This process
can be accelerated if the hydrodynamic flow of solvent occur under osmotic pressure gradients.
Lipid insoluble drugs cross through membrane by filtration if their molecular size is smaller than the
diameter of the pores.
Majority of the cell have very small in pore size ( 4 A0
) and drug with MW more than 100 –200, can not
penetrate through this pore. However, the capillaries of blood vessels ( except Blood brain barrier) have
lager in (40 A0
) size and most of the drug even albumin can diffuse through this capillaries. The diffusion
of drugs solely depend on the rate of blood flow.
Special transport: (carrier mediated or pinocytosis):
Drug +carrier = complex; then translocate.
Polar molecules (Hydrophilic) coated with hydrophobic layer thus facilitate transport i.e. Ionopheres.
Carrier transport is specific, saturable and competitively inhibited by the analogues which use the same
carrier.
Carrier mediated

13. 2/23/2018
DIPTO KUMER SARKER
13
13
1. Activate transport
2. Facilitated diffusion
A. Active transport:
 Requires energy
 Inhabitation
 Transports solute
 Selective accumulation of the substance on one side of the membrane.
It requires energy, is inhibited by metabolic poisons, and transports the solute against its electrochemical
gradient (low to high), resulting in selective accumulation of the substance on one side of the membrane.
Levodopa and methyl dopa are actively absorbed from the gut by the aromatic amino acid transporter. In
addition, the body has developed some relatively nonselective transporters, like P-glycoprotein (P-gp), to
deal with xenobiotics.
B. Facilitated diffusion:
The drug forms a complex with a component of the biological membrane The complex is carried through
membrane, the drug is released, and the carrier molecule returns to the membrane surface. This diffusion
does not require energy. The transporter translocates the substrate in the direction of electrochemical
gradient( high to low).
It is more rapid than simple diffusion, translocates even no diffusible substrate. It occurs in renal tubes
and hepatic regions. Thisdiffusion id non specific.
C. Pinocytosis
It is the process of transport across the cell in particulate form by formation of vesicles. This is applicable
to proteins and other big molecules, and contributes little to transport of most drugs, barring few like
vit-B12 which is absorbed from the gut after binding to intrinsic factor (a protein).
Absorption
Absorption is movement of the drug from its site of administration into the circulation.
Effect of route of administration on drug administration:
 Oral
Epithelial lining:
 The effective barrier to orally administered drugs is the epithelial lining of the gastrointestinal
tract, which is lipoidal.
 Nonionized lipid soluble drugs, e.g. ethanol are readily absorbed from stomach as well as
intestine at rates proportional to their lipid : water partition coefficient.
 Acidic drugs, e.g. salicylates, barbiturates, etc. are predominantly unionized in the acid gastric
juice and are absorbed from stomach.
 Basic drugs, e.g. morphine, quinine, etc. are largely ionized and are absorbed only on reaching
the duodenum.

14. 2/23/2018
DIPTO KUMER SARKER
14
14
Even for acidic drugs absorption from stomach is slower, because
 The mucosa is thick.
 Covered with mucus.
 The surface area is small.
Presence of food dilutes the drug and retards( slow down) absorption.
Absorption interfere by delay emptying. Most drugs are absorbed better if taken in empty stomach. E.g.:
Tetracycline should be taken on an empty stomach, at least 1 hour before or 2 hours after meals or
snacks. Do not take tetracycline with food, especially dairy products such as milk, yogurt, cheese, and ice
cream.
However, there are some exceptions, e.g. fatty food greatly enhances lumefantrine absorption. Highly
ionized drugs, e.g. gentamicin, neostigmine are poorly absorbed when given orally.
 Certain drugs are degraded in the gastrointestinal tract, e.g. penicillin G by acid, insulin by
peptidases.
 Absorption also effected by drug-drug interaction. This causes
 formation of insoluble complexes, e.g.tetracyclines and iron preparations with calcium salts
and antacids.
 Such interaction can be minimized by administering the two drugs at 2–3 hr intervals.
 Absorption is also effected by alteration of intestinal microbial flora.
 Drugs can also alter absorption by gut wall effects:
o altering motility (anticholinergics, tricyclic antidepressants, opioids, metoclopramide) or
o causing mucosal damage (neomycin, methotrexate, vinblastine).
 Topical site
Absorption in topical site depending on the lipid solubility of the drugs. Only few drugs can penetrate
through the intact(whole) skin, e.g. nitroglycerin, hyoscine, estradiol.
Corticosteroid applied over skin can have systemic effect and pituitary adrenal suppression.
Absorption can be promoted by rubbing the skin, also incorporation of smoothening agent or
vasodialating agent enhance absorption.
Abraded surfaces readily absorb drugs, e.g. tannic acid applied over burnt skin.
Cornea is permeable to lipid soluble, unionized physostigmine but not to highly ionized neostigmine.
Drugs applied as eye drops may get absorbed through the nasolacrimal duct.
Mucous membranes of mouth, rectum, vagina absorb lipophilic drugs.
 Subcutaneous and intramuscular:

15. 2/23/2018
DIPTO KUMER SARKER
15
15
Drug deposited directly into the vicinity of the capillaries. Lipid soluble drug directly passes across the
whole surface of the capillary membrane.
Capillaries are highly porous- do not obstruct ionized molecules, even large molecules are absorbed
through lymphatic system.
Drug those can not absorbed through oral route can absorbed through subcutaneous or intramuscular
route.
Absorption from s.c. site is slower than that from i.m. site, but both are generally faster and more
consistent/ predictable than oral absorption.
Application of heat and muscular exercise accelerate drug absorption by increasing blood flow, while
vasoconstrictors retard absorption.