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Introduction

Drug absorption

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Introduction

Drug absorption
Routes of administration

Oral
Parenteral
Topical

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Mechanisms of drug transport

Intercellular (transcellular) transport

Passive transport

Passive diffusion
Pore transport
Ion-pair transport
Facilitated diffusion

Active transport

Primary
Secondary

Symport
Antiport

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Mechanisms of drug transport

Intracellular (paracellular) transport

Tight junctions of epithelial cells
Persorption

Endocytosis

Pinocytosis
Phagocytosis

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Passive diffusion

Passive transport is a type of membrane transport that does not require energy to move substances across cell membranes.
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.

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Passive 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

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Passive 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.

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Passive diffusion

Equation follows first order kinetics hence passive diffusion process is first order process.

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Pore transport

Pore transport is a process that moves small molecules through cell membranes via pores or channels
Connective transport/ 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-
Absorption- low molecular size
Water soluble drugs- urea, water, sugars
Chain like or linear compounds absorbed by filtration.

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Ion pair transport

Is a process that increases the rate at which polar drugs can cross lipid membranes.
It also improves the bioavailability of hydrophilic ionizable drugs.
Complex- liphophilic and water soluble
Absorbed by passive diffusion.
Example- Propranolol- oleic acid, quaternary ammonium compounds.

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Carrier-Mediated transport

Carrier-mediated transport is a process that moves molecules across cell membranes using carrier proteins. It's a combination of diffusion and a chemical reaction.
carrier protein binds to a molecule or ion
The carrier protein changes shape
The molecule or ion is released on the other side of the membrane

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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

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A- Passive diffusion

B- Carrier mediated transport

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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.

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Carrier-Mediated transport

Characteristics

Mixed order kinetics
Bioavailability decreases with increasing dose
Example – Vit B1, B2, B12
Absorption window

Two types

Facilitated diffusion
Active transport

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Carrier-Mediated transport

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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
Monocarboxylic acid transporter	Pravastatin

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Facilitated diffusion

Characteristics

Downhill transport
Faster than passive diffusion
Driving force- concentration gradient
Passive process
Energy independent
Vitamin B1, B2 & B12
Intrinsic factor-B12

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Active transport diffusion

Two Types

Primary active transport
Secondary active transport

Primary 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

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Active transport diffusion

Primary active transport

Ion transporters

ATP driven ion pump- proton pump
Two types

Organic anion transporter

atrovastatin

Organic cationic transporter

diphenhydramine

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Active transport diffusion

Primary active transport

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

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Active transport diffusion

Secondary active transport

No direct requirement of ATP
Concentration gradient
Two types

Symport (co transport)
Antiport (counter transport)

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Active transport diffusion

Secondary active 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

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Active transport diffusion

Characteristics

Uphill transport
Faster than passive diffusion
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.

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Active transport diffusion

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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)

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Factors affecting drug absorption

Pharmaceutical factors

Physicochemical properties of drug
Dosage form related factors

Patient related factors

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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

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Physicochemical factors

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

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Physicochemical factors

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

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Physicochemical factors

Diffusion layer model

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

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Physicochemical factors

Diffusion layer model

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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

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Physicochemical factors

Diffusion layer model

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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

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Physicochemical factors

Diffusion layer model

The rate of dissolution is given by Noyes & Whitney

Where,

dc/dt= dissolution rate of the drug

K= dissolution rate constant

C_s= concentration of drug in stagnant layer

C_b= concentration of drug in the bulk of the solution at time t

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Physicochemical factors

Diffusion layer model

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.

(C_s – C_b )= conc. gradient for diffusion of drug.

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Physicochemical factors

Diffusion layer model

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.

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Physicochemical factors

Diffusion layer model

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. C_b=0 and rate of dissolution is maximum.
Under sink conditions, if the volume and surface area of the solid are kept constant, then

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Physicochemical factors

Diffusion layer model

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.

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Physicochemical factors

Diffusion layer model

Dissolution under sink & non sink conditions

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Conc. of dissolved drug

Time

first order dissolution under non-sink condition

zero order dissolution under sink condition

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Physicochemical factors

Diffusion layer model

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

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Physicochemical factors

Diffusion layer model

Hixon & Crowell’s cubic root law
takes into account the particle size decrease and change in surface area,

W₀^1/3 – W^1/3 = K_t

Where,

W₀=original mass of the drug

W=mass of drug remaining to dissolve at time t

K_t=dissolution rate constant.

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Physicochemical factors

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.

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Physicochemical factors

Danckwert’s Model

The Danckwert’s model is expressed by equation

Where,

m = mass of solid dissolved

Gamma (γ) = rate of surface renewal

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Physicochemical factors

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

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Physicochemical factors

Factors affecting drug dissolution and dissolution rate

Physicochemical properties of drug
Dosage form factors

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Physicochemical 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.

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Physicochemical factors

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

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Physicochemical factors

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

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Physicochemical factors

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

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Physicochemical factors

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.

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Physicochemical factors

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.

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Physicochemical factors

pH partition hypothesis

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

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Physicochemical factors

pH partition hypothesis

Drug pka and GIT pH

Henderson-Hasselbach equations

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Physicochemical factors

pH partition hypothesis

Drug pKa and GIT pH

Shore et al

Therapeutic ratio (R) given by

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Physicochemical factors

pH partition hypothesis

Drug pka and GIT pH

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

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Physicochemical factors

pH partition hypothesis

Drug pka and GIT pH

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

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Physicochemical factors

pH partition hypothesis

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

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Physicochemical factors

pH partition hypothesis

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

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Physicochemical factors

pH partition hypothesis

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Physicochemical factors

Liphophilicity and drug absorption

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

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Physicochemical factors

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

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Physicochemical factors

Limitations of pH partition hypothesis

Presence of virtual membrane pH

Virtual membrane pH different than luminal pH
pH absorption curve

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Basic drugs

Acidic drugs

pH of GI Lumen

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Physicochemical factors

Limitations of pH partition hypothesis

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

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Physicochemical factors

Limitations of pH partition hypothesis

Presence of aqueous unstirred diffusion layer

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Aqueous GIT fluid

Aqueous unstirred diffusion layer

Lipoidal biomembrane

Blood

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Physicochemical factors

Drug permeability & absorption

Absorption is expressed by

Where

M = amount of drug absorbed

P_eff= effective membrane permeability

A = surface area available for absorption

C_app= apparent luminal drug concentration

t_res = residence time of drug in GI lumen

Three major properties determine permeability

Lipophilicity
Polarity of drug
Molecular size

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Physicochemical factors

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

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Physicochemical factors

Drug stability

Shelf life of drug during storage
Destabilization in GIT

Stereochemical nature of drug

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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

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Dosage form factors

Method of granulation

Wet granulation
Dry granulation
APOC method

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Dosage form factors

Compression force

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Rate of drug dissolution

Compression force

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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.

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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

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Dosage form factors

Nature and type of dosage form

Solutions
Emulsions
Suspensions
Powders
Capsules
Tablets
Coated tablet
Enteric coated tablet
Sustained release tablet

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Patient related factors

Gastrointestinal tract

Function
Length 450 cm
Stomach
Small intestine
Large intestine

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Patient related factors

Stomach

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

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Patient related factors

Small Intestine

Large surface area

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Patient related factors

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

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Patient related factors

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

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Patient related factors

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

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Patient related factors

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

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Patient related factors

Gastric Emptying

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

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Patient related factors

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

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Patient related factors

Intestinal transit

Peristaltic movement- promotes absorption
Delayed intestinal transit is desirable

SR products
Drugs dissolves in intestine
Absorption window
Slow absorption

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Patient related factors

Gastrointestinal pH

Disintegration- Enteric coated
Dissolution
Absorption
Stability

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Patient related factors

Disease state

Gastrointestinal diseases

Achlorhydria
Celiac disease
Crohn’s disease
Malabsorption
GI infections
Colonic diseases
GIT surgery

Cardiovascular diseases
Hepatic diseases

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Patient related factors

Blood flow to GIT

28% of cardiac output
Sink condition
Food alters blood flow

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Patient related factors

GIT content

Food drug interaction

Fluid volume

Large fluid volume results better dissolution, rapid gastric emptying

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Delayed	Decreased	Increased	Unaffected
Aspirin	Penicillins	Griseofulvin	Methyldopa
Paracetamol	Erythromycin	Diazepam	Propylthiouracil
Diclofenac	Tetracyclines	Vitamins
Digoxin	Iron

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Patient related factors

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)

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Patient related factors

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

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Patient related factors

First Pass Effect

Bacterial enzymes
Gut wall enzymes

Alcohol dehydrogenase
Phase I and Phase II enzymes

Hepatic enzymes

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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

Absorption of Drug

2/5/2025

92 of 102

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

Absorption of Drug

2/5/2025

93 of 102

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,

Absorption of Drug

2/5/2025

94 of 102

Topical Administration

Skin

Surface area 2 sqm
Blood supply 1/3^rd
Stratum corneum
Mechanisms of absorption

Transcellular (passive diffusion)
Intercellular (paracellular)
Transappendageal

Through hair follicles, sweat gland, sebaceous gland

Absorption of Drug

2/5/2025

95 of 102

Topical Administration

Factors

Skin conditions
Composition of topical vehicle
Application conditions
Environmental factors

Absorption of Drug

2/5/2025

96 of 102

Topical Administration

Skin conditions

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

Absorption of Drug

2/5/2025

97 of 102

Topical Administration

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

Absorption of Drug

2/5/2025

98 of 102

Topical Administration

Drug administered

Nitroglycerine, lidocaine, testosterone

Iontophoresis

Delivery of ionic drug into the body -an electric current

Sonophoresis

Delivery of drug- under influence of ultrasound

Absorption of Drug

2/5/2025

99 of 102

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

Absorption of Drug

2/5/2025

100 of 102

Pulmonary Administration

Large surface area of alveoli
High perfusion
High permeability
Bronchodilators, steroids, antiallergics
Factors

pH
Lipid soluble- passive diffusion
Ionic, polar- pore transport
Particle/ globule size

Absorption of Drug

100

2/5/2025

101 of 102

Intranasal Administration

Less surface area
High perfusion
High permeability
Peptides, proteins, Bronchodilators, steroids, antiallergics
Factors

pH (5.5-6.5)
Lipid soluble- passive diffusion
Ionic, polar- pore transport
Molecular size
Mucociliary clearance

Absorption of Drug

101

2/5/2025

102 of 102

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.

Absorption of Drug

102

2/5/2025