Absorption

Contents
 Cell membrane
 Absorption mechanism,
 Oral drug absorption,
 pH partition hypothesis,
 Factors affecting:
 Physicochemical,
 dosage form related,
 patient related.
 Drug absorption through other routes:
 transdermal,
 nasal,
 buccal,
 Ocular
 sublingual.
 In-vitro, In-situ and In-vivo models for drug absorption studies.
2Absorption of Drug4/13/2018

Introduction
pH = 1 - 3
pH = 5 - 7
disintegration
disintegration
disso-
lution
disso-
lution
absorption
intestinal
metabolism
absorption
hepatic
metabolism
clearancefaeces
Pharmacological effect
gastric emptying rate
intestinal transit rate

Introduction
 Drug absorption

Introduction
 Drug absorption
 Routes of administration
 Oral
 Parenteral
 Topical

Cell Membrane

Mechanisms of drug transport
 Intercellular (transcellular) transport
 Passive transport
 Passive diffusion
 Pore transport
 Ion-pair transport
 Facilitated diffusion
 Active transport
 Primary
 Secondary
 Symport
 Antiport

Mechanisms of drug transport
 Intracellular (paracellular) transport
 Tight junctions of epithelial cells
 Persorption
 Endocytosis
 Pinocytosis
 Phagocytosis

Passive diffusion
 Non ionic diffusion
 Driving force- concentration gradient
 Drug movement- kinetic energy of molecule
 Energy independent process
 Expressed by Fick’s first law of diffusion
 The drug molecules moves from a region of higher
concentration to one of lower concentration until
equilibrium is attained and the rate of diffusion is directly
proportional to the concentration gradient across
membrane.

Passive diffusion
 Fick’s first law of diffusion
 Characteristics of passive diffusion
 Downhill transport
 Process- energy independent & non saturable
 Drug transfer directly proportional to conc gradient
 Greater the area & lesser thickness of membrane, faster
diffusion
 Process is rapid over short distance and slower over long
distance
)(/
CC
h
DAK
dt
dQ
GIT
wm


Passive diffusion
 Fick’s first law of diffusion
 Characteristics of passive diffusion
 Equilibrium is attained when the concentration on
either side of membrane becomes equal.
 Rate of transfer of unionised drug is more than ionised.
 Greater partition coefficient of drug, faster the
absorption.
 Drug diffusion is rapid- volume of GI fluid is low.
 Process id dependent on molecular size of the drug.
)(/
CC
h
DAK
dt
dQ
GIT
wm


Passive diffusion
 Fick’s first law – non sink condition
 Sink condition
 Equation follows first order kinetics hence passive
diffusion process is first order process.
 Hydrophobic molecules > Small uncharged polar
molecules> Large uncharged polar molecules
 Ions – not absorbed by passive diffusion.
GITPC
dt
dQ


Pore transport
 Connective transport/ bulk flow/ filtration
 Transport of molecules into the cell through the
protein channels present in the cell membrane.
 Characteristics
 Driving force- hydrostatic pressure/ osmotic difference
across the cell membrane.
 Water flux promotes transport- solvent drag.
 Absorption- low molecular size, less than 100.
 Water soluble drugs- urea, water, sugars
 Chain like or linear compounds absorbed by filtration.

Ion pair transport
 Formation of reversible neutral complex with
endogenous ions (mucin).
 Complex- liphophilic and water soluble
 Absorbed by passive diffusion.
 Example- Propranolol- oleic acid, quaternary
ammonium compounds.

Carrier-Mediated transport
 Faster than passive diffusion
 Carriers- component of membrane
 Reversible/ covalent bonding
 Carrier-solute complex-
 transverse across membrane
 dissociation of solute
 carrier –returns to original site
 Carriers – proteins/ enzymes
A- Passive diffusion
B- Carrier mediated transport

 Characteristics
 Carrier protein has uncharged outer surface.
 Carrier protein soluble in lipid.
 Carrier- any direction - work efficiently.
 Transport process is structure specific.
 System is structure specific.
 Limited carrier- competition – similar agents.
 System is capacity limited.

 Characteristics
 Mixed order kinetics
 Bioavailability decreases with increasing dose
 Example – Vit B1, B2, B12
 Absorption window
 Two types
 Facilitated diffusion
 Active transport

Intestine Transporters and Examples of Drugs Transported
Transporter Examples
Amino acid transporter Gabapentin D-Cycloserine
Methyldopa Baclofen
L-dopa
Oligopeptide transporter Cefadroxil Cephradine
Cefixime Ceftibuten
Cephalexin Captopril
Lisinopril Thrombin inhibitor
Phosphate transporter Fostomycin Foscarnet
Bile acid transporter S3744
Glucose transporter p-Nitrophenyl beta
D-glucopyranoside
P-glycoprotein efflux Etoposide Vinblastine
Cyclosporin A
Monocarboxylic acid
transporter
Salicylic acid Benzoic acid
Pravastatin

Facilitated diffusion
 Characteristics
 Downhill transport
 Driving force- concentration gradient
 Passive process
 Energy independent
 Vitamin B1, B2 & B12
 Intrinsic factor-B12

Active transport diffusion
 Two Types
 Primary active transport
 Secondary active transport
 Direct ATP requirement
 Process transfers only ion/ molecule in one direction
 Hence called uniporter
 Absorption of glucose
 Two types
 Ion transporters
 ABC transporters

 Ion transporters
 ATP driven ion pump- proton pump
 Two types
 Organic anion transporter
 atrovastatin
 Organic cationic transporter
 diphenhydramine

 ABC (ATP binding cassette) transporters
 Transport small molecules (drug and toxins) out of cell.
 Exsorption
 Efflux pumps
 ABC transporter example- p-glycoprotein (P-gp)
 P-gp called multidrug resistant protein
 Drug- anticancer drugs

 No direct requirement of ATP
 Concentration gradient
 Two types
 Symport (co transport)
 Antiport (counter transport)

 Symport
 Both molecules moves in same direction
 Na+ - glucose symporter : uses potential energy of sodium
concentration gradient to move glucose against concentration
gradient.
 H+ - coupled peptide transporter – absorption of peptide like
drugs- beta lactam antibiotics.
 Antiport
 Molecules moves in opposite direction

 Characteristics
 Uphill transport
 Energy required
 Inhibited by metabolic poison
 Fluorides, cyanide,
 Endogenous material absorbed.
 Drugs- 5 flurouracil, 5-flurobromacil via pyrimidine
transport.
 Methyl dopa, levodopa via L-amino acid transport system.
 Enalapril via peptide carrier system.

Endocytosis
 Engulfing extracellular material.
 Fats, starch, insulin, vitamin A, D, E, K.
 Drug absorbed in lymphatic system- bypass first pass.
 Two types
 Phagocytosis (cell eating)
 Pinocytosis (cell drinking)

Factors affecting drug absorption
 Pharmaceutical factors
 Physicochemical properties of drug
 Dosage form related factors
 Patient related factors

Physicochemical factors
 Drug solubility & dissolution rate
 Rate determining steps
 Dissolution- hydrophobic like griseofulvin, spironolactone
 Permeation- hydrophilic like neomycin
 BCS- Amidon et al
 Class I drug: high solubility/ high permeability
 Class II drugs: low solubility/ high permeability
 Class III drugs: high solubility/ low permeability
 Class IV drugs: low solubility/ low permeability

 Drug solubility & dissolution rate
 Intrinsic solubility
 Maximum amount of solute dissolved in a given solvent under
standard conditions of temperature, pressure and pH.
 Static property
 Dissolution rate
 Amount of solid substance that goes into solution per unit
time under standard conditions of temperature, pH and
solvent composition and constant surface area.
 Dynamic process

 Theories of dissolution
 Dissolution
 Solid substance solubilises in a given solvent.
 Mass transfer from the solid surface to the liquid phase.
 Theories
 Diffusion layer model
 Surface renewal theory
 Limited solvation theory

 Two steps
 Solution of the solid to form stagnant film or diffusive
layer which is saturated with the drug
 Diffusion of the soluble solute from the stagnant layer to
the bulk of the solution; this is RDS in drug dissolution

 Diffusion layer or stagnant
film
 Formation of thin film or
layer at solid-liquid interface
is diffusion layer
 Diffusion layer is saturated
with drug
 Rapid step
 Diffusion of soluble solute
 From stagnant layer to bulk
of the solution
 Slower step, hence rate
determining

 In dissolution theory, it is assumed that an
 Solute molecules exists in the concentrations
from Cs to Cb. beyond the static layer at x
greater than h,
 mixing occurs in the solution and the drug is
found in uniform concentration, Cb
throughout the bulk phase.
 At x= 0 drug in the solid is in equilibrium
with drug in diffusion layer.
 The gradient in the concentration with the
distance is constant as shown in fig.
 This is the gradient represented by the term,
(Cs-C)/h.
 When Cb is considerably lower than Cs, the
system is represented by Sink conditions

 The rate of dissolution is given by Noyes & Whitney
Where,
dc/dt= dissolution rate of the drug
K= dissolution rate constant
Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the solution at time t
)( bS CCk
dt
dC


 Modified Noyes-Whitney’s Equation
Where,
D= diffusion coefficient of drug.
A= surface area of dissolving solid.
Kw/o= water/oil partition coefficient of drug.
V= volume of dissolution medium.
h= thickness of stagnant layer.
(Cs – Cb )= conc. gradient for diffusion of drug.
 bS
OW
CC
Vh
DAK
dt
dC
 /

 Sink conditions
 In the derivation of equation it is assumed that
 D and h remains constant
 the static diffusion layer thickness is altered by the force of
agitation at the surface of the dissolving tablet.
 Surface area A never remains constant as powder, granule or
tablet dissolves and it is difficult to obtain an accurate
measure of A.
SC
h
DA
dt
dC


 Sink conditions
 This is first order dissolution rate process, for which the
driving force is concentration gradient.
 This is true for in-vitro dissolution which is characterized by
non-sink conditions.
 The in-vivo dissolution is rapid as sink conditions are
maintained by absorption of drug in systemic circulation i.e.
Cb=0 and rate of dissolution is maximum.
 Under sink conditions, if the volume and surface area of the
solid are kept constant, then

 Sink conditions
 Under sink conditions, if the volume and surface area of the
solid are kept constant, then
 This represents that the dissolution rate is constant under sink
conditions and follows zero order kinetics.
K
dt
dC


 Dissolution under sink & non sink conditions
Conc.ofdissolveddrug
Time
first order dissolution under non-
sink condition
zero order dissolution under
sink condition

 Sink conditions can be achieved by
 Bathing solid in fresh solvent from time to time
 Increasing volume of dissolution fluid
 Removing dissolved drug by partitioning
 Adding water miscible solvent
 Adding adsorbents

 Hixon & Crowell’s cubic root law
 takes into account the particle size decrease and change
in surface area,
W0
1/3 – W1/3 = Kt
Where,
W0=original mass of the drug
W=mass of drug remaining to dissolve at time t
Kt=dissolution rate constant.

 Danckwert’s Model
 Turbulence in dissolution medium exists at solid/liquid
interface
 Dankwert takes into account the eddies or packets that
are present in the agitated fluid which reach the solid-
liquid interface, absorb the solute by diffusion and carry
it into the bulk of solution.
 These packets get continuously replaced by new ones
and expose to new solid surface each time, thus the
theory is called as surface renewal theory.

 Danckwert’s Model
 The Danckwert’s model is expressed by equation
Where,
m = mass of solid dissolved
Gamma (γ) = rate of surface renewal
DCCA
dt
dm
dt
dC
V bS )( 

 Interfacial Barrier model
 An intermediate concentration can exist at the interface as a
result of solvation mechanism and is function of solubility
 Interfacial barrier model is expressed by equation
Where,
G = dissolution rate per unit area
Ki = effective interfacial transport constant
)( bSi CCKG 

 Factors affecting drug dissolution and dissolution rate
 Physicochemical properties of drug
 Dosage form factors

 Particle size and effective surface area
 Particle size and surface area are inversely related to
each other.
 Two types of surface area
 Absolute surface area which is the total surface area of any
particle.
 Effective surface area which is the area of solid surface
exposed to the dissolution medium.
 Effective surface area is directly related to the
dissolution rate.
 Greater the effective surface area, more intimate the
contact between the solid surface and the aqueous
solvent and faster the dissolution.

 Polymorphism & amorphism
 When a substance exists in more than one crystalline
form, the different forms are designated as polymorphs
and the phenomenon as Polymorphism.
 Stable polymorphs has lower energy state, higher M.P.
and least aqueous solubility.
 Metastable polymorphs has higher energy state, lower
M.P. and higher aqueous solubility.
 Eg. Chloramphenicol palmitate B

 Polymorphism & amorphism
 Amorphous form of drug which has no internal crystal
structure represents higher energy state and greater
aqueous solubility than crystalline forms.
 E.g.- amorphous form of novobiocin is 10 times more
soluble than the crystalline form.
 Thus, the order for dissolution of different solid forms of
drug is –
amorphous > metastable > stable

 Hydrates/ Solvates
 The stoichiometric type of adducts where the solvent
molecules are incorporated in the crystal lattice of the solid
are called as the solvates.
 When the solvent in association with the drug is water, the
solvate is known as hydrate.
 The organic solvates have greater aqueous solubility than the
nonsolvates.
 E.g. – chloroform solvates of griseofulvin is more water soluble than
their nonsolvated forms

 Salt form of drug
 Dissolution rate of weak acids and weak bases can be enhance
by converting them into their salt form.
 With weakly acidic drugs, a strong base salt is prepared like
sodium and potassium salts of barbiturates and sulfonamides.
 With weakly basic drugs, a strong acid salt is prepared like the
hydrochloride or sulfate salts of alkaloidal drugs.

 pH partition hypothesis
 Theory states that for drug compounds molecular weight
greater than 100 dalton, primarily transported across
biomembrane by passive diffusion and process of absorption
is governed by:
 pKa of drug
 Lipid solubility of unionised drug
 pH at the absorption site
 Most drugs are- weak electrolytes
 Ionisation depends on the pH of the biological fluid.
 Unionised with sufficient lipid soluble drug cross barrier until
equilibrium is attained.

 Theory is based on following assumptions
 GIT is a simple lipoidal barrier
 Larger fraction of unionised drug, faster absorption
 Greater the partition coefficient of unionised drug, better absorption
 Drug pka and GIT pH
 Unionised fraction is function of pKa of drug and pH of GIF
 Low pKa of acidic drug- strong acid- greater ionisation
 Higher pKa of basic drug- strong base- greater ionisation

 Henderson-Hasselbach equations
100
101
10
ioniseddrug%
drug][unionised
drug][ionised
logpKapH
acidsFor Weak
)(
)(
pKapH
pKapH





100
101
10
ioniseddrug%
drug][ionised
drug][unionised
logpKapH
basesFor Weak
)(
)(
pHpKa
pHpKa






 Drug pKa and GIT pH
 Shore et al
 Therapeutic ratio (R) given by
)(
)(
Plasma
Git
a
101
101
C
C
R
acidsFor Weak
pKapH
pKapH
Plasma
Git





)(
)(
b
101
10
R
basesFor Weak
Plasma
Git
pHpKa
pHpKa
Plasma
Git
C
C





 Generalisations regarding ionisation & absorption of acids
 Very weak acids (pKa > 8): unionised at all pH values, absorption is
rapid and independent of GI pH. Pentobarbital, hexobarbital,
phenytoin, ethosuximide
 Moderately weak acid (Pka, 2.5 – 7.5): absorption is pH dependent,
better absorbed from acidic pH (pH<pKa). Cloxacillin, aspirin,
ibuprofen, phenylbutazone
 Strong acid (Pka< 2.5): ionised in the entire pH range of GIT, poorly
absorbed. Disodium cromoglycate

 Generalisations regarding ionisation & absorption of Bases
 Very weak bases (pKa < 5): unionised at all pH values, absorption is
rapid and independent of GI pH. Theophylline, caffeine, oxazepam,
diazepam, nitrazepam
 Moderately weak bases (Pka, 5 – 11): absorption is pH dependent,
better absorbed from alkaline pH. Morphine, chloroquine,
imepramine, amitriptyline
 Strong bases (Pka > 11): ionised in the entire pH range of GIT, poorly
absorbed. Mecamylamine, Guanethidine

 Aqueous Solubility
 Total aqueous solubility (St): Sum of concentration of ionised and
unionised drug in solution.
 The solubility of unionised form of drug is known as intrinsic
solubility of drug.
 For acidic drugs
 For basic drugs
]101[SS )(
aT
pKapH 

]101[SS )(
bT
pHpKa


 Conclusions and generalisations
 For weakly acidic drugs
 When pH > pKa, St >> Sa, ionisation of drug increases
 When pH = pKa, St = 2Sa, 50 % ionisation
 When pH< pKa, St = Sa, drug exists as unionised form
 For basic drugs
 When pH > pKa, St = Sb, drug exists as unionised form
 When pH = pKa, St = 2Sb, 50 % ionisation
 When pH< pKa, St >> Sb, ionisation of drug increases

 Liphophilicity and drug absorption
 Hydrophilic-lipophilic balance- optimum absorption
 Partition coefficient
 Rapid rate of absorption (Ko/w, 0.12-100): Thiopental (67%),
Phenylbutazone (54%), Benzoic acid (54%), salicylic acid
(60%).
 Moderate rate of absorption (Ko/w, 0.002 – 0.03): Aspirin
(21%), Theophylline (30%), Sulphanilamide (24%)
 Slow rate of absorption (< 0.002): barbituric acid (5%),
sulphaguanidine (2%)

 Limitations of pH partition hypothesis
 Presence of virtual membrane pH
 Absorption of ionised drugs
 Influence of surface area and residence time of drug
 Presence of aqueous unstirred diffusion layer

 Presence of virtual membrane pH
 Virtual membrane pH different than luminal pH
 pH absorption curve
Basic drugsAcidic drugs
pH of GI Lumen
pHofGILumen

 Absorption of ionised drugs
 pH absorption curve
 Absorption of ionic drugs
 Large lipophilic group
 Influence of surface area and residence time of drug
 Acidic drugs- stomach
 Basic drugs- intestine
 Area available
 Acidic & basic drugs absorbed well in intestine, long residence

 Presence of aqueous unstirred diffusion layer
Aqueous GIT fluid
Aqueous unstirred
diffusion layer
Lipoidal biomembrane
Blood

 Drug permeability & absorption
 Absorption is expressed by
 Where
M = amount of drug absorbed
Peff = effective membrane permeability
A = surface area available for absorption
Capp = apparent luminal drug concentration
tres = residence time of drug in GI lumen
 Three major properties determine permeability
 Lipophilicity
 Polarity of drug
 Molecular size
resappeff tACPM 

 Drug permeability & absorption
 Rule of five by Lipinski et al
 Molecular weight of drug < 500
 Lipophilicity of drug, log P < 5
 Number of H bond acceptors < 10
 Number of H bond donors < 5

 Drug stability
 Shelf life of drug during storage
 Destabilization in GIT
 Stereochemical nature of drug

Dosage form factors
 Disintegration time
 Manufacturing variables
 Excipients
 Manufacturing processes
 Method of granulation
 Compression force
 Intensity of packing of capsule content
 Nature and type of dosage form
 Product age and storage condition

Dosage form factors
 Method of granulation
 Wet granulation
 Dry granulation
 APOC method

Dosage form factors
 Compression force
Rateofdrugdissolution
A B C D
Compression force

Dosage form factors
 Intensity of packing of capsule contents
 Diffusion of GI fluids into the tightly filled capsules
creates a high pressure within the capsule resulting in
rapid bursting and dissolution of contents.
 On other hand, it shows that capsule with finer particles
and intense packing have poor drug release and
dissolution rate due to decrease in pore size of the
compact and poor penetrability by the GI fluids.

Dosage form factors
 Excipients
 Vehicle
 Diluents
 Binders and granulating agent
 Disintegrants
 Lubricants
 Coating agents
 Suspending agents/ Viscosity imparters
 Surfactants
 Buffers
 Complexing agents
 Colorants
 Crystal growth inhibitors

Dosage form factors
 Nature and type of dosage form
 Solutions
 Emulsions
 Suspensions
 Powders
 Capsules
 Tablets
 Coated tablet
 Enteric coated tablet
 Sustained release tablet

Patient related factors
 Gastrointestinal tract
 Function
 Length 450 cm
 Stomach
 Small intestine
 Large intestine

 Stomach
 Structure- bag like
 Small surface area
 Acidic pH- favors absorption of acidic drugs
 Acidic pH – favors dissolution of basic drugs
 Limited gastric residence

 Small Intestine
 Large surface area

 Small Intestine
 Large surface area (200 sqm)
 Length of small intestine (300-500 cm)
 Greater blood flow (1 l/min)
 Favourable pH range (5-7.5)
 Slow peristaltic movement
 Prolonged residence time (3-6h)
 High permeability

 Large Intestine
 Small surface area (0.15 sqm)
 Length (110 cm)
 blood flow (0.02 l/min)
 pH range (6-8)
 Residence time (6-12 h)
 Important in absorption of poorly soluble drug and SRDF

 Age
 Infants
 Gastric pH high
 Less intestinal surface area
 Low Blood flow
 Elderly
 Altered gastric emptying
 Decreased intestinal surface area
 Decreased blood flow
 Higher incidence of achlorhydria and bacterial overgrowth

 Gastric Emptying
 Passage of drug from stomach to small intestine
 Rate limiting step for absorption
 Rapid gastric emptying increases bioavailability
 Rapid gastric emptying is advisable where
 Rapid onset of action is desired
 Dissolution occurs in intestine
 Drug unstable in stomach
 Drug best absorbed in intestine
 Gastric emptying can be promoted by taking drug on empty
stomach

 Delay in gastric emptying is advisable where
 Food promotes dissolution and absorption
 Disintegration and dissolution promoted by gastric fluid
 Drug dissolves slowly
 Drug irritates gastric mucosa
 Drug absorbed in proximal part of intestine
 Gastric emptying rate
 Gastric emptying time
 Gastric emptying half life
 Barium sulphate is used to determine gastric emptying

 Factors influencing gastric emptying
 Volume of meal
 Composition of meal
 Physical state & viscosity of meal
 Temperature of meal
 Gastrointestinal pH
 Electrolytes & osmotic pressure
 Body posture
 Emotional state
 Exercise
 Disease state
 Drugs

 Intestinal transit
 Peristaltic movement- promotes absorption
 Delayed intestinal transit is desirable
 SR products
 Drugs dissolves in intestine
 Absorption window
 Slow absorption

 Gastrointestinal pH
 Disintegration- Enteric coated
 Dissolution
 Absorption
 Stability

 Disease state
 Gastrointestinal diseases
 Achlorhydria
 Celiac disease
 Crohn’s disease
 Malabsorption
 GI infections
 Colonic diseases
 GIT surgery
 Cardiovascular diseases
 Hepatic diseases

 Blood flow to GIT
 28% of cardiac output
 Sink condition
 Food alters blood flow

 GIT content
 Food drug interaction
 Fluid volume
 Large fluid volume results better dissolution, rapid gastric
emptying
Delayed Decreased Increased Unaffected
Aspirin Penicillins Griseofulvin Methyldopa
Paracetamol Erythromycin Diazepam Propylthiouracil
Diclofenac Tetracyclines Vitamins
Digoxin Iron

 GIT content
 Normal GI constituents
 Mucin decreases absorption of drug
 Bile salts increases absorption of lipid soluble drugs
 Drug-drug interactions
 Physicochemical
 Adsorption
 Complexation
 pH change
 Physiological
 Decreased GI transit (Propantheline)
 Increased gastric emptying (Metoclopramide)
 Altered GI metabolism (Antibiotics)

 First Pass Effect
 The loss of drug through biotransformation by GIT and Liver
during its passage to systemic circulation.
 Luminal Enzymes
 Digestive enzymes
 Enzymes present in gut fluid include intestinal and
pancreatic secretions.
 Hydrolases
 Hydrolyses esters
 chloramphenicol palmitate to
chloramphenical
 Inactivates proteins

 First Pass Effect
 Bacterial enzymes
 Gut wall enzymes
 Alcohol dehydrogenase
 Phase I and Phase II enzymes
 Hepatic enzymes

Buccal & Sublingual Administration
 Sublingual Route
 Under tongue and allowed to dissolve
 Buccal Route
 Between cheek & gum
 Barrier for absorption- oral epithelium
 Drug absorbed by passive diffusion
 Advantages
 Rapid absorption
 No first pass

Buccal & Sublingual Administration
 Factors
 Biphasic solubility of drug is required.
 pH of saliva (6)
 Binding of drug to oral mucosa
 Storage compartment
 Thickness of oral epithelium
 Surface area
 Taste of medicament
 Antianginals, Antihypertensives, Analgesics,
Bronchodilators

Rectal Administration
 Unconscious patients and children
 If patient is nauseous or vomiting
 Easy to terminate exposure
 Absorption may be variable
 Good for drugs affecting the bowel such as laxatives
 Irritating drugs contraindicated
 Dosage- solutions, suppositories
 pH (8)
 Surface area
 Bypass first pass (lower half)
 Analgesics, Bronchodilators,

Topical Administration
 Skin
 Surface area 2 sqm
 Blood supply 1/3rd
 Stratum corneum
 Mechanisms of absorption
 Transcellular (passive diffusion)
 Intercellular (paracellular)
 Transappendageal
 Through hair follicles, sweat gland, sebaceous gland

 Factors
 Skin conditions
 Composition of topical vehicle
 Application conditions
 Environmental factors

 Skin conditions
 Thickness of stratus corneum
 Presence of hair follicles
 Trauma
 Hydration of skin
 Age
 Skin microflora
 Skin pH
 Skin surface lipids
 Anatomical site

 Composition of topical vehicle
 Vehicle/ base
 Permeation enhancers
 Application conditions
 Rubbing
 Occulsion
 Loss of vehicle
 External factors
 Environmental humidity and temperature
 Grooming
 Exposure to chemicals
 Chronic use of certain drug

 Drug administered
 Nitroglycerine, lidocaine, testosterone
 Iontophoresis
 Delivery of ionic drug into the body -an electric current
 Sonophoresis
 Delivery of drug- under influence of ultrasound

Intramuscular Administration
 Factors
 Vascularity of the injection site
 Blood flow to site
 Lipid solubility and ionisation
 Molecular size of drug
 Volume of injection and drug concentration
 pH, composition and viscosity of injection vehicle

Pulmonary Administration
 Large surface area of alveoli
 High perfusion
 Bronchodilators, steroids, antiallergics
 Factors
 pH
 Lipid soluble- passive diffusion
 Ionic, polar- pore transport
 Particle/ globule size

Intranasal Administration
 Less surface area
 High perfusion
 Peptides, proteins, Bronchodilators, steroids,
antiallergics
 Factors
 pH (5.5-6.5)
 Lipid soluble- passive diffusion
 Ionic, polar- pore transport
 Molecular size
 Mucociliary clearance

Bibliography
 D. M. Bramhankar and S. B. Jaiswal. Biopharmaceutics and
Pharmacokinetics A Treatise. Delhi;Vallabh Prakashan. 2010
 Jambhekar SS, Breen PJ. Basic Pharmacokinetics. London;
Pharmaceutical Press. 2009.
 Shargel L, Wu-Pong S, Yu ABC. Applied biopharmaceutics and
Pharmacokinetics. McGraw Hill. 2007.
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