A

SEMINAR PRESENTATION
ON

DIFFUSION AND ITS IMPORTANCE

IN PHARMACEUTICAL PROCESSES

AISSMS COLLEGE OF PHARMACY

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 CONTENT

 INTRODUCTION

 DIFFUSION

 STEADY STATE DIFFUSION

 DIFFUSION THROUGH MEMBRANE

 PROCEDURE AND METHOD FOR ASSESSING DRUG DIFFUSION

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PHARMACEUTICAL IMPORTANCE OF DIFFUSION

Drug absorption and elimination

Drug release from various dosage forms.
Osmosis
Diffusion as mixing mechanism.
Ultra filtration and dialysis
Bioadhesion mechanism
Diffusion batteries
Filtration and integrity testing of filters.
Evaluation of antimicrobial.

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OBJECTIVE
 Define diffusion and describe relevant example in the
pharmaceuticals science and the practice of pharmacy.
 Understand the process of dialysis, osmosis, and ultra filtration
as they apply to the pharmaceutical sciences and practice of
pharmacy.
 Describe the mechanism of transport in the pharmaceuticals
system and identify which one of are diffusion based.
 Define and understand the fick’s law of diffusion and there
application.
 To understand diffusion coefficient, permeability.
 Describe various driving forced in diffusion.

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Study the different pharmaceutical process which based

on the diffusion mechanism.

 To study different method used for study of diffusion.

 Study different process such as evaluation of aerosol ,

 Mechanisms which involve diffusion such as

bioadhesion, drug release, diffusion batteries .

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 INTRODUCTION
Diffusion is also defined as a process of the mass transfer of the
individual molecule of a substance brought about by the random
molecular motion associated with a driving force such as
concentration gradients.

Free diffusion of the substance through liquids, solids, and the

membranes are process of considerable interest in the
pharmaceutical sciences. Mass transfer phenomenon applying in the
pharmaceuticals sciences include the release and dissolution of the
drug from the tablet, powder, and the granules; lyophilysation,
ultatrafiltration, and other mechanical processes; release form the
ointment, pastes suppository bases. The dosage forms additives
through coating, packaging, films, plastic containers, seals, and caps;
and permeation and the distribution of drug molecules in the
living systems.
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DIFFUSION
 Basic principle of diffusion is based on the thermodynamic

consideration.
 Diffusion of a dissolved substance from a region of the higher

concentration to region of the lower concentration following random

molecular motion and result in the decrease in the free energy of the
system.
 We many conveniently illustrate that by the simple experiment of the

diffusion of the dye from a solution in to the pure water solvent.

 The” random walk “nature .

 Net result in the formation of homogeneous solution.

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STEADY-STATE DIFFUSION

 Thermodynamic basis –

Mass transfer is the movement of molecules in an applied driving

force. Convective and diffusion mass transfer are important to
many pharmaceuticals processes.
mass transfer is a kinetic process, occur in the system that are not
in equilibrium.

Chemical potential A.1 > A .2

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FICK’S LAWS OF DIFFUSION

The amount of material, M of material flowing through a unit cross

sections, S, of a barrier in a unit time, t, Is known as a flux , j;

The flux, in unit turn, is proportional to the concentration gradient,

dC/dx ;

Where D is a diffusion coefficient in cm2/sec.

C is the concentration in g/cm3

D is affected by the concentration ,temp., pressure, solvent property, and

chemical nature of diffusant.

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FICK’S SECOND LAW
 Fick’s second law of diffusion forms the basis for most mathematical
models of diffusion processes. One often wants to examine the rate of
change of mass transport that emphasizes the change in
concentration with time at a definite location rather than the mass
diffusing across a unit area of barrier in unit time is known as fick’s
second law.

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APPLICATION

 Equations based on Fick's law have been commonly used to model

transport processes in foods, neurons and biological membranes ,
biopolymers , pharmaceuticals ,dosage forms etc.
 Theory of all diffusion based methods is based on solutions of Fick's
equation.
 A large amount of experimental research in polymer science and food
science have been going on where diffusion plays important role. 

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STEADY STATE

A system is said to be at steady state ,if the condition of the system do

not change with time.
An important condition in diffusion is that of steady state. Ficks' first
law gives the flux in the state of steady state of flow.

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DIFFUSION DRIVING FORCES

 There are many diffusional driving forces in the pharmaceutical

system.

Driving force example

concentration Passive diffusion, drug

dissolution.

pressure osmotic drug release.

Temperature Lyophilization

Electrical potential electrophoresis ,

iontophoresis.

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PROCEDURE AND APPARATUS FOR ASSESSING DRUG
DIFFUSION

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Diffusion cell for permeation
This cell is used to study the diffusion through the
stratum corneum (forearm) of various permeates e.g.
gases, liquids and gels.
Kept at constant temperature.

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 DIFFUSION THROUGH MEMBRANE

 There are several ways that a solute or a solvent can traverse a

physical or biologic membrane. The first e.g. is diffusion through the

polymeric membrane. The matter through a solid barrier can occur by
simple molecular permeation or by the movement through pores and
channels.

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Steady diffusion across a thin film and diffusional resistance

 Yu and Amidon are two scientist developed an analysis for steady state

diffusion across a thin film as it relate to diffusional resistance. as shown

in figure, steady diffusion across a thin film of thickness h. In this case
the diffusion coefficient is considered constant because the solution on
the both side of the thin film are dilute. The concentration on the both
side of the film , Cd and the Cr, are kept constant and both side mix
well. now diffusion occur through the region of high conc. To the lower
conc. i.e. from Cd to Cr. after sufficient time steady state is achieve and
the conc. are const. at all points in the film.

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At steady state

dC/dt= 0 , so fick’s second law become

D. d2e/dz2 =0

Now integrating this by twice using the conditioned that at

z=0, C=Cd and z=h, C=Cr, yield

J=D/h ( C1-C2)

THE TERM H/d IS THE DIFFUSIONAL RESISTANCE

And is dinoted by R.

Permeability and diffusional resistance are opposite to each other.

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PHARMACEUTICAL IMPORTANCE OF DIFFUSION

 Osmosis - Osmosis is the diffusion of water down its concentration gradient.

 If two solutions of different concentration are separated by a semi-permeable

membrane which is permeable to the smaller solvent molecules but not to the larger
solute molecules, then the solvent will tend to diffuse across the membrane from
the less concentrated to the more concentrated solution. This process is called
osmosis.
 Osmosis is of great importance in biological processes where the solvent is water.

The transport of water and other molecules across biological membranes is essential
to many processes in living organisms.
 Osmotic drug release system .

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The process of
osmosis

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Osmotic Controlled Drug Delivery System
 A number of design options are available to control or modulate the
drug release from a dosage form

 Osmotic systems utilize the principle of osmotic pressure for the

delivery of drugs. Drug release from these systems is independent of
pH and other physiological parameter to a large extent .

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Different types of osmotic systems-Design, mechanism and uses.

 1) Osmotic Pump - The water penetrates inside the dosage form at

the rate determined by the fluid permeability of the membrane and
osmotic pressure of core formulation. This will result in formation of
saturated solution of drug within the core, which is dispensed at a
controlled rate from the delivery orifice in the membrane.

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2) Controlled-porosity osmotic pump - Water-soluble additives dissolve
after coming in contact with water, resulting in an in situ formation of a micro
porous membrane. The resulting membrane is substantially permeable to both
water and dissolved solutes and the mechanism of drug release was found to be
osmoticaly control diffusion.

Micro porous membrane

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3) Sandwiched Osmotic tablets-

The middle push layer swells and drug is released from delivery
orifices

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Ultra filtration and dialysis
Dialysis is primarily used to provide an artificial
replacement for lost kidney function (renal replacement
therapy)due to renal failure.
Dialysis works on the principles
Diffusion of solutes,
Ultrafiltration of fluid across a semi permeable membrane
 Actual process.
The counter-current flow of the blood and dialysate
maximizes the concentration gradient of solutes between the
blood and dialysate, which helps to remove more urea and
creatinine from the blood.

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 Types –
 There are two primary types

Hemodaylasis and Peritoneal dialysis

 In hemodialysis, the patient's blood is pumped through the blood compartment of a

dialyzer, exposing it to a semipermeable membrane. The cleansed blood is then

returned via the circuit back to the body. Ultra filtration occurs by increasing the
hydrostatic pressure across the dialyzer membrane. This usually is done by applying a
negative pressure to the dialysate compartment of the dialyzer. This pressure gradient
causes water and dissolved solutes to move from blood to dialysate, and allows the
removal of several liters of excess fluid during a typical 3 to 5 hour treatment

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 Peritoneal dialysis

A sterile solution containing minerals and glucose is run through a tube into the peritoneal cavity,
where the peritoneal membrane acts as a semipermeable membrane. The dialysate is left there
for a period of time to absorb waste products, and then it is drained out through the tube and
discarded. This cycle or "exchange" is normally repeated 4-5 times during the day.
 Ultrafiltration

The process of water removal from the blood stream is called ulrtafiltration; the fluid removed is the
ultrafiltrate .  The UF during dialysis is performed for the purpose of removing water accumulated
by ingestion of fluid or by metabolism of food during the interdialytic period. It is essential to
prescribe and control the fluid removal rate so that total fluid removed during dialysis will be equal
to the total fluid gained .

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DRUG RELEASE

Considering the sink condition the factor affecting the apparent rate of the

release of the core molecule

 The diffusion path length

 Molecular collision radius of the diffusing substance

 Microscopic viscosity of the diffusion environment

 Surface area of the dosage form in contact with the sink conditions medium

 And concentration difference between the start of the molecular diffusion

and sink condition.

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DRUG RELEASE
DIFFUSION IN HYDROGEL- Hydrogel is water swollen network polymer familiar
hydrogel includes gelatin desserts soft contact lenses. All hydrogel regardless of there
actual origin, may be thought of an being composed of hydrophilic monomer unit
linked to form the water soluble polymer and then cross linked to form the insoluble
polymer network and it is manly use in controlled drug delivery.

DIFFUSION IN HYDROGELS-

Hydrogels can be designed to release drug by various mechanism,

erosion of the gel

hydrolysis of the drug from the polymer backbone

most common mechanism is the passive diffusion .

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The swollen hydrogel (diffusion in swollen hydrogel )
The most important parameter governing the diffusion
coefficient in the swollen gel is the water content. In
general the diffusion coefficient increase with the
increasing in water content , it have very low value in dry
gel.
hydrogels are studied for the development of self-
regulated insulin delivery system, which releases the
insulin in response to changing glucose concentration

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Rate-controlled delivery system
 Rate-controlled delivery system deliver a drug at a predetermined rate for a specific time period.

 Delivery either can systemically or locally .

 There are commonly used method are

1) diffusion systems

2) dissolution systems

3) osmotic system

4) swelling systems

5) erosion-controlled systems

6) controlled release by stimulation

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Diffusion system
 In these systems, the release rate of a drug is determined by its diffusion through an inert membrane barrier, usually
an insoluble polymer.
 There are two type
1) reservoir devices
2) matrix devices

 reservoir devices – the release of drug here governed by the first

law of diffusion ( fick’s).

Diffusion reservoir devices has been some of the widely used and most
successful oral system. Common methods used to developed such type
is microencapsulation and film coating tablets.
e.g. of microencapsulation both diffusion and dissolution.
Diffusion controlled reservoir devices also used in parental ( e.g.
levonorgesterol implants), ocular, transdermal route.

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 Diffusion controlled implants –
 Implants are most commonly used for parental administration over the significantly

prolong time of period of time. (e.g.).

 In that the drug release governed by diffusion .

 Two type of devices that we have seen that is reservoir and matrix type

Transdermal patches –
 Have several advantages.

Provide large area for diffusion,

noninvasive, easy to apply and remove,

long term drug release.

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Drug release from tablet
Disintegration,deaggrigation,dissolution.
Diffusion also plays important role.
The rate at which solid dissolves in the solvent was
given by Noyes and Whitney
Aqueous diffusion layer or stagnant liquid film.

solid layer

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DIFFUSION AND BIOADHESION
 Natural and synthetic bioadhesive polymers that can adhare to hard or soft tissue have

been used for many years in dentistry, orthopedics, ophthalmology and surgical
procedures.
 mucoadhesive.

 There are various mechanism by which the adhesion is take place.

Electronic theory
Fracture theory
Adsorption
Wetting theory
Diffusion theory

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 The mean diffusional pathway can be calculated by

S= (2tD) 1/2

T= contact time , the rate of penetration is directly proportional to

the d.c of mucosal glycoprotein’s structure into the polymer matrix
and polymer strand into the mucosal matrix.

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DIFFUSION AS A MIXING MECHANISM

 There are various mechanism of mixing that is for both fluid as well as for the solid.

 In case of the liquid the mechanism are,

Bull transport

Turbulent mixing

Laminar mixing

molecular diffusion
 molecular mixing - the primary mechanism for fluid mixing at molecular level is

diffusion resulting from the thermal motion of the molecules. When it occur with
conjunction with the laminar flow result in complete mixing. The mechanism is given
by the fick’s law of diffusion.

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 DRUG ABSORPTION AND ELIMINATION
 Passive Transport

Passive transport requires no energy from the cell. Examples include

the diffusion of oxygen and carbon dioxide, osmosis of water, and
facilitated diffusion.

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 facilitated diffusion
 Facilitated diffusion of the drug takes place through proteins, or

assemblies of proteins, embedded in the plasma membrane. These

transmembrane proteins form a water-filled channel through which the
ion can pass down its concentration gradient.
 Many ion channels open or close in response to binding a small

signaling molecule or "ligand". Some ion channels are gated by

extracellular ligands; some by intracellular ligands. In both cases, the
ligand is not the substance that is transported when the channel opens

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Absorption via BBB

Lipophilic drug.

Lipophobic drug.

Lipophilicity can be increase by chemical means by

conjugation with lipophilic drug carrier .

Use of dihydropyridine system.

DIHYDROPYRIDINE SYSTEM

Diffusion as the mechanism.

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DIFFUSION TESTING

Diffusion test used to evaluate the filter which are use

to filter the large volume.
This test measure the amount of the air flows through
the wet membrane.
The mechanism is based on the fick's first law of
diffusion.
Actual process.
If at low pressure the large amount of air is displace
then filter is damaged more.

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DIFFUSION BATTERIES

Diffusion batteries have been used to evaluate the

aerosol in concern with the partials size.
Consist of series of the cylindrical tube containing
series of the screen.
Diffusion coefficient , d is given by
D = K T Cc
3 Dp pay u
Amount of particles retain , the concentration is
determined.

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AGAR DIFFUSION TEST

The agar diffusion test, or the Kirby-Bauer disk-

diffusion method, is a means of measuring the effect
of an antimicrobial agent against bacteria grown in
culture.
Zone of inhibition .
MIC

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RESEARCH AND WORK.
 Gastro-intestinal diffusion tablet: Influence of polyoxyethyleneglycol 400. international
journal of pharnaceutics volume 129 isseu 1-2, 8 March 1996, Pages 279-282
 Controlled Release Formulation of Tramadol Hydrochloride Using Hydrophilic and
Hydrophobic Matrix System.
 Osmotic Flow Through Asymmetric Membrane: A Means for Controlled Delivery of
Drugs With Varying Solubility Anil K. Philip and Kamla Pathak Department of
Pharmaceutics, Rajiv Academy for Pharmacy,Mathura-286001,UttarPradesh,India.
 Osmotic Drug Delivery: An Update a review article by M.C.Goyel Parikh R.K, Shah R.
Y. Pharma info.net.
 Transdermal Patch and Method For Delivery Of Vitamin B12 Inventors: Jon D
zeltman, patents doc.
 Hydrogels as controlled drug delivery systems: Synthesis, crosslinking, water
and drug transport mechanism CS Satish, KP Satish, HG Shivakumar Year :
2006  |  Volume : 68  |  Issue : 2  |  Page : 133-140

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REFERENCES
 Patricks J. Sinko, Martins physical pharmacy and pharmaceutical sciences, fifth
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 Brian W. Barry , drug and pharmaceutical science dermatological formulation ,
perceutanous absorption, volume 18 Dekker series , 1983, 49,50,57.
 Peter J . Tarcha , polymer for controlled drug delivery , 1990 cps press., 2, 22,3.
 Leon Lachman , Herbert A. Lieberman ,Joseph L. Kanig , the theory and practice of
industrial pharmacy, third edition , Varghese publication house mumbai 14, 3-
6,15,158-159.
 Remington the science and practice of pharmacy , 21th edition, volume 1 , Indian
edition, Lippincott William's & Wilkins ,
 www. Aaps pharmascience .com
 P. Arnaud, I. Guillard, D. Brossard and J. C. Chaumeil, Gastro-intestinal diffusion
tablet: Influence of polyoxyethyleneglycol 400 , international journal of
pharmaceutics volume 129,issue 1-2 , 8 March 1996, Pages 279-282 .

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 http;//en.wikipedia.org/wiki/dialysis
 Koichi linoyo, Keishi Gotohko,Higasitani. Powder technology hand
book, dekker series, New york 1990 . 33,34
 Robinson and lee . Controlled drug delivery , fundamentals and
application , 2nd edition revised and expanded, volume 19 , Marcel
Dekker series, 180,182.

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THANK YOU

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