Drug

Absorption
Objectives
At the end of the session students should be able to:
a) List & discuss the common routes of drug administration.
b) Explain the absorption pattern of common routes of drug
administration.
c) Describe various dosage forms & their absorption
patterns.
d) Discuss novel drug delivery systems like transdermal drug
delivery etc.
e) Discuss factors affecting drug absorption
f) Emphasize factors influencing bioavailability and
bioequivalence
g) Explain the concept of Henderson Hasselbach equation.

Dr. Sajid Hussain

 PHARMACOKINETICS
uPharmacokinetics is the quantitative study of drug movement in, through and
out of the body.

uPharmacokinetic processes include (ADME)

I. Absorption of drug
II. Distribution of drug
III. Metabolism of drug
IV. Excretion of drug
Why do you need to know
pharmacokinetics?
Pharmacokinetics is significant for
• Route of drug administration
• Dose of drug
• Latency of onset
• Time of peak action
• Duration of action
• Frequency of drug administration
ROUTES OF DRUG ADMINISTERATION
ORAL ROUTE- The most common route of drug administration eg-
Paracetamol, ORS
ADVANTAGES
• Drug is given through oral cavity. Safe
Convenient- self- administered, pain free and
noninvasive
• Economical- compared to other parentral
routes Usually good absorption- takes place
along the whole length of the GI tract No need
for sterilization
DISADVANTAGES
• Some drugs have slow and erratic absorption
• slow action - can not used in emergency
• Irritable and unpalatable drugs- nausea and
vomiting
• Cannot be used in Unco-operative, vomiting and
unconscious patients
• Some drugs are destroyed in the GIT/Liver
• Some drugs are inefficiently absorbed eg.
streptomycin
• First-pass effect- Due to Biotransformation
• Food–Drug interactions and Drug-Drug
interactions
Sublingual route eg- glyceryl trinitrate
RECTAL ROUTE –
Drugs that are administered rectally as a suppository- eg.- Diazepam,
indomethacin, paraldehyde, ergotamine

ADVANTAGES DISADVANTAGES
• Used in children Little or no first • Inconvenient
pass effect (ext haemorrhoidal
• Absorption is slow and erratic
vein)
• Irritation or inflammation of
• Used in vomiting or
rectal mucosa can occur
unconscious
• Higher concentrations rapidly
achieved
PARENTERAL ROUTES
Direct delivery of drug in to systemic circulation without intestinal mucosa

• Intradermal (I.D.) (into skin) e.g. BCG vaccine

• Subcutaneous (S.C.) (into subcutaneous tissue) e.g. Insulin
• Intramuscular (I.M.) (into skeletal muscle) e.g. diclofenac
• Intravenous (I.V.) (into veins) e.g. parenteral nutrition
• Intra-arterial (I.A.) (into arteries) e.g. anticancer drugs
• Intrathecal (I.T.) (cerebrospinal fluids ) e.g. morphine
• Intraperitoneal (I.P.) (peritoneal cavity) e.g rehydration fluid
• Intra - articular (Synovial fluids) e.g. Hydrocortisone
Parenteral route- eg of drugs- atropine, edrophonium
INTRAVENOUS ROUTE (IV) eg. Midazolam
ADVANTAGES
• IV is the most common parenteral
route. For drugs that are not absorbed
orally.
• Avoids first-pass metabolism by the
liver.
• Intravenous delivery permits a rapid
effect and a maximal degree of control
over the circulating levels of the drug.
• Titration of dose with response.
• large quantities can be given, fairly pain
free (100% bioavailability) Absorption
phase is bypassed
DISADVANTAGES
• Unlike drugs in the GI tract, those that
are injected cannot be retrieved by
strategies such as emesis…
• IV injection may also induce hemolysis
or cause other adverse reactions by
the too-rapid delivery of high
concentrations of drug to the plasma
and tissues also vital organs like heart,
brain etc.
• Thrombophlebitis of vein and necrosis
of adjoining tissue if extravasation
occurs
Inhalational route eg- salbutamol,
anesthestics
• Inhalation provides the rapid delivery of a drug
across the large surface area of the mucous
membranes of the respiratory tract and
pulmonary epithelium, producing an effect
almost as rapidly as with IV injection.

• This route of administration is used for drugs that

are gases (for example, some anesthetics) or
those that can be dispersed in an aerosol.

• This route is particularly effective and convenient

for patients with respiratory complaints (such as
asthma, or chronic obstructive pulmonary
disease) because the drug is delivered directly to
the site of action and systemic side effects are
minimized.

• Examples of drugs administered via this route

include albuterol, and corticosteroids, such as
fluticasone.
INTRAMUSULAR ROUTE Large skeletal muscle-
Deltoid, gluteus maximus- eg. streptomycin

ADVANTAGES DISADVANTAGES
• Absorption reasonably uniform • Only upto 10ml drug given
• Rapid onset of action • Can cause Local pain and
• Mild irritants can be given abcess
• First pass avoided • Expensive
• Gastric factors can be avoided • Infection
• Nerve damage
• Local hematoma can occur in
anticoagulant treated pt.
TOPICAL

*transdermal route can be used as a local or systemic route

Transdermal drug delivery- novel drug delivery system

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

Transdermal patches of GTN, fentanyl,

Nicotine, hyoscine, clonidine and estradiol are
available.
Usually applied on upper arms, chest, abdomen,
buttocks and thighs

Other novel drug delivery system are; dermojet, Pellet

implant (eg.testosterone), silastic rings (eg.norplant),
etc. 10/25/22 16
 Dosage forms
What are dosage forms?
Dosage Form (DF) is defined as the physical form of a
dose of a chemical compound used as a drug or
medication intended for administration or consumption.
Talet, capsule, vial, MDI, cream, Patch…

Different tablet dosage forms-

Chewable tablets-can be chewed or wallowed,
ingredients must be pleasent tasting.
Dispersible tablets- the tablet is dropped in a
small quantity of water, wherein it disperses
quickly; the solution is then gulped.
Sublingual tablets-put under the tongue, the drug
is rapidly absorbed from the mouth.
Enteric coated tablet- the tablet is coated with a
mate rial that does not dissolve in the acidic
medium of the stomach; the tablet disintegrates
only on reaching the duodenum.
Sustained/Extended release tablets- These
contain drug particles which are coated to be
dissoved at a later time.

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 How the drug moves from its site
administration to the site of action

Figure- shows the vascular pathway of drugs

absorbed from various systemic routes of
administration and sites of first pass
metabolism

The pattern of absorption of

Oral drug (eg-tablet) is subjected to first
pass metabolism in intestinal wall and liver,
while
approximately half of that absorbed from
the rectal suppository passes through liver.
Drug through Systemic route (ampoule) is
exposed to first pass metabolism in lungs,
10/25/22 but its extent is minor for most drugs.
 Common routes of drug administration and their absorption pattern

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 Common routes of drug administration & their absorption pattern

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Factors governing choice of route of administration?

Factors governing choice of route

i. Physical and chemical properties of drug
ii. Site of desired action
iii. Rate and extent of absorption of drug from
different routes
iv. Effect of digestive juices and first pass metabolism.
v. Rapidity with which the response is desired
vi. Condition of the patient
 DRUG ABSORPTION

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 Components of Pharmacokinetics- ADME

Absorption: First, absorption from the site of administration permits

entry of the drug (either directly or indirectly) into plasma.

Distribution: Second, the drug may reversibly leave the bloodstream

and distribute into the interstitial and intracellular fluids.

Metabolism: Third, the drug may be biotransformed through

metabolism by the liver or other tissues.

Elimination: Finally, the drug and its metabolites are eliminated from
the body in urine, bile, or feces.

Using knowledge of pharmacokinetic parameters, clinicians can

design optimal drug regimens, including the route of administration,
dose, frequency, and duration of treatment.
 Orally administered drugs are
exposed to drug metabolizing
enzymes in the intestinal wall
and liver (where they first
reach through the portal
vein)- this is first pass
metabolism.

It can be avoided by
administering the drug
through sublingual,
transdermal or parenteral
routes

10/25/22
 Drug absorption and Factors governing it

Drug absorption ; Absorption concerns the processes of entry of

a drug into the systemic circulation from the site of its
administration.
Factors governing drug absorption;

u Aqueous Solubility. Ability to diffuse through lipid bilayers (lipid

solubility)
u is important for most drugs; however, water solubility can influence
u permeation through aqueous phases.
u Concentration gradient. Diffusion down a concentration gradient—only
free, unionized drug forms contribute to the concentration gradient.
u Surface area and vascularity. Important with regard to absorption of
drugs into the systemic circulation. The larger the surface area and the
greater the vascularity, the better is the absorption of the drug.
u pH (ionization)
u Routes of drug aministration
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 How drugs are transported
across membranes?
Passive Diffussion of unionised drugs is the most common and
important mode of drug transport across membranes.

• Drugs diffuse passively down their concentration gradient

• Diffusion can be influenced signilicantly by the lipid-water

partition cotfficient of the drug.

Filtration is the bulk flow of solvent and solute through channels

in the membrane.
a. It is seen with small molecules (usually with a molecular
weight <100 Dalton) that can pass through the pores.

Facilitated diffusion is movement of a substance down a

concentration gradient. a. It is carrier mediated, specific, and
saturable; it does not require energy.

Active transport is an energy-dependent process that can move

drugs against a concentration gradient through protein-mediated
transport systems.
Active transport occurs in only one direction and is saturable eg-
sugars, amino acids, and nucleosides.
 Drugs need to cross all the barriers to reach
the site of action

For drugs in CNS- it has to cross the

blood brain barrier- Only the small
molecular weight/unionized form of a drug can
diffuse to any significant degree across biologic
membranes.

For drugs to act in fetus- it has to cross the

placental barrier

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Influence of pH on Ionization of weakly acidic / Basic Drugs
(Henderson Hasselbach’s equation)
Many drugs are weak acids or weak bases and
can exist in either nonionized or ionized forms
in an equilibrium, depending on the pH of the
environment and the pKa (the pH at which the
molecule is 50% ionized
and 50% nonionized)
–– Only the nonionized (uncharged) form of a
drug crosses biomembranes.
–– The ionized form is better renally excreted
because it is water soluble.

For Weak Acids and Weak Bases

Ionized (Protonated) = Water soluble
Nonionized (Deprotonated) = Lipid soluble
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Pharmacological implications of Henderson Hasselbach’s equation:
Most drugs are weak electrolytes, that is, their ionization is pH dependant.
• Weakly acidic drugs which form salts with cations ( example: sodium
phenobarbitone, sodium sulphadiazine ,potassium penicillin V) ionise more at
alkaline pH.
• Weakly basic drugs which form salts with anions(example: atropine sulphate,
ephedrine hydrochloride, chloroquine phosphate) ionize more at acidic ph.
• Ions being lipid insoluble do not diffuse across a biological membrane.
• Acidic drug example aspirin(pKa =3.5) are largely unionized at acidic gastric pH and
are absorbed from the stomach.
• Basic drugs like atropine(pKa =10) are largely unionized and absorbed only when
they reach small intestine.
• Acidic drug are ionized more in alkaline urine – do not diffuse in the kidney and
are excreted faster. Accordingly, basic drugs are excreted faster if urine is acidified.
This principle is used in treatment of drug overdose.
 PHARMACOKINETICS
PLASMA CONCENTRATION TIME CURVE
Bioavailability
• It is a measure of the fraction of administered dose of
a drug that reaches the systemic circulation in the
unchanged form.
• Bioavailability of a drug injected intravenously(IV) is
100%.
• Calculated from comparing plasma level of a drug
after a particular route of administration with plasma
drug level achieved by IV injection.
 Bioavailability

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Factors that influence bioavailability of a drug
1. First pass hepatic metabolism
2. Solubility of a drug
3. Chemical stability
4. Nature of drug formulation.
Bioavailibility variation assumes practical significance for drugs with low
safety margin (digoxin) or where dosage needs precise control.

Bioequivalence: Oral formulations of a drug from different manufacturers or different

batches from the same manufacturer may have the same amount of the drug
(chemically equivalent) but may not yield the same blood levels- biologically
inequivalent. Two preparations of a drug are considered bioequivalent when the rate
and extent of bioavailability of the active drug is not significantly differerent under
suitable test conditions.
• Summarize-
Routes of drug administration
Dosage forms
Absorption/ permeation
Hendersen Hesselbach’sequation
Bioavailability

• References / Further reading

Katzung & Trevor’s Basic and Clinical Pharmacology. 15th. Ed. (2018)
Illustrated reviews Pharmacology, Ed. Lippincott. 7th Ed. (2018)
Essentials of Pharmacology – KD Tripathi 8th Ed. (2018)
Internet resource

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