DRUG DELIVERY

GELS
BY:NIKUNJA BASINI PATI
M.PHARM 2nd SEM
PHARMACEUTICS

POLYMERS :These are the stretch/chain of monomers,

linked covalently to each other.
POLYMERS are extensively used in drug
delivery for :rheology control,
control of drug release rate,
stabilization of colloidal drug
carriers,
solubilization of sparingly soluble
drugs.

POLYMER GELS:- frequently used to

describe thick or non flowing systems.
They are specially recognized for their

HYDROGELS

:-

these are 3-D, water swollen polymers

composed of mainly hydrophilic homopolymers/
copolymers.
They are rendered insoluble due to
presence of chemical or physical cross links.
Generally suitable for
molecular stabilization of sparingly soluble
drugs, for bioadhesion, for desired rheological
properties.

Generally used hydrogels:

PVA - Poly(vinylalcohol)
PHEMA Poly(2-hydroxyethyl methacrylate)
PEO - Poly(ethylene oxide)
PEG - Poly(ethylene glycol)
PNVP Poly(N vinyl 2- pyrollidone)
PEVAc - Poly(ethylene- co- vinyl acetate)
PMMA - Poly(methyl methacrylate)

PAA - Poly(acryl amide)

Classification based on :

Nature of side groups (as neutral & ionic),

Network morphology(as amorphous,

semicrystalline, hydrogen- bonded structures,
supermolecular structures, & hydro-colloidal
aggregates.

Network structures (as macroporous,

microporous, or nonporous)

Hydrogels have four key properties:swelling degree,

permeability &

biocompatibility,
swelling kinetics.

Hydrogels are used due to their:excellent biocompatibility,

high water content,
rubbery nature,
protection to the drug &
control release of solute.

Mainly used as devices to provide timeindependent,

sustained release , controlled release of
bioactive agents
by manipulation of the polymer
composition and the device geometry.

Thereby, most important characteristics in

evaluating the ability of polymeric gels for
controlled release system are :network permeability and swelling
behavior.

Parameters that define the structure and

properties of swollen hydrogels are :Polymer volume fraction in the swollen state

Effective molecular weight of the polymer chain

between cross-linking points M (this is related to
the degree of cross linking)

And network mesh or pore size (distance

between consecutive cross linking points and
provides a measure of porosity of the network)

Mc ,

Cross linked structure of a

hydrogel
where, Mc is the molecular
wt. of polymer chains between cross

Equilibrium swelling theories :Neutral hydrogels :Swelling of these gels has been depicted using
a Guassian distribution of polymer chains.
it is governed by the elastic retractive forces of
the polymer chains and the thermodynamic
compatibility of polymer and the solvent
Thereby, total free energy change upon swelling
is written as:
G = Gelastic + Gmix

It was further developed taking into

consideration,
(chemical potential changes in the solvent),
(polymer- solvent interaction)
M (molecular weight of the linear polymer chains
between cross links) e.t.c.

Ionic hydrogels:These contain anionic/ cationic side groups

attached.
For e.g., Anionic gels ---- the side groups are
unionized below the pKa value.
Above this value they get ionized ---gels swell due to development of a large osmotic
swelling force due to presence of ions.
In these gels,
Higher the ionic content ----------more will be
swelling.

The various models have been depicted for

swelling of ionic gels, taking into consideration
(change in chemical potential of the solvent)
I (Ionic strength of polymers)
Ka & Kb (dissociation constant)
pH of the environment.

pH

Rubber elasticity theory:(

Elastic behavior of cross linked polymers has

been analyzed using -------classical thermodynamics,
statistical thermodynamics, and
phenomenological models & various equations
have been depicted.
like, for a system of n chains, the
change in the Helmholtz free energy upon elastic
deformation can be written as:

Network pore size Calculations : In controlling the rate release of a drug.

A direct technique for measuring this is
quasielastic laser-light scattering / electron microscopy.
Indirect ones are mercury porosimetry, rubber elasticity
measurement, or equilibrium swelling experiments.
Based on crosslink density, this can be determined as,

where , is the network pore size

is the elongation of polymer chains in any direction
ro is the end-end distance of polymer chains
between cross links.

Diffusion in hydrogels
described by classical Fickian
diffusion theory which is expressed as,
In case of Macroporous hydrogels :have large pores (0.1 to 1 m)
these water filled pores are sufficient for
drug diffusion.
drug transport in terms of network porosity(),
tortuosity ( ) and diffusion coefficient of solute in
pure solvent and partition coefficient.

Microporous hydrogel:have pore size (100 1000)

drug transport occurs due to combination
of molecular diffusion and convection in the water
filled pores.
the rate of diffusion coefficient in the
membrane & pure solvent can be related to the
ratio of the solute and pore radius.

Where,

Nonporous hydrogels:have pore size (10 100 )

here chains are densely packed.
Drug transport only by diffusion.
Diffusion theory relates
the ratio of the diff. coefficient of the
solute in the membrane to the diff. coefficient of
the solute in the pure solvent
to the degree of hydration of the
membrane .

Preparation of hydrogels :Hydrogel properties are adjusted through

an appropriate mix of hydrophobic & hydrophilic
monomer, ionic monomers & cross linkers.
Neutral Hydrophilic
Monomers
Hydroxyalkyl acrylates
Hydroxyalkylmethaacrylate
s

Neutral Hydrophobic
Monomers
Acrylics
Methacrylics

N- substituted acrylamides

Vinyl acetate

N- vinyl 2-pyrrolidone

Acrylonitrile
Styrene

2,4- pentadiene-1-ol

19

Ionic monomers
Anionic -----------Acrylic acid
Methacrylic acid
Crotonic acid
Sodium
styrenesulfonate
Cationic------------Vinylpyridine
Aminoethyl
methacrylates
2- methacryloyloxytrimethylammonium chloride

Crosslinking
monomers
N, N
methylenebisacrylamide
Ethylene glycol
dimethacrylates
2, 2- (pphenylenedioxy)diethyl
dimethacrylate
Divinylbenzene
Triallylamine
Methylenebis(4- phenyl
isocyanate)

Hydrogel synthesis:chemical crosslinking of linear

polymers.
radiation crosslinking of linear
polymers.
physical crosslinking of linear
polymers.
copolymerization/ crosslinking
synthesis from monomers.
a) bulk/ solution

polymerization
b) suspension
polymerization

Classification:Hydrogel based drug delivery systems are

classified as,
Diffusion controlled systems
reservoir systems
matrix systems.

Drug release from a hydrogel-based reservoir delivery

system

Drug release from a hydrogel based matrix delivery

system

Swelling controlled systems.

Chemically controlled systems
erodible drug delivery systems
pendent chain systems.
Environmentally responsive systems.

Drug release from a hydrogel- based swelling controlled

systems

Drug release from hydrogel-based erodible delivery

Applications :In drug delivery systems

(major goal is delivery of drugs at
constant rate)
Varieties of hydrogels ,
wide differences in their properties and
their responsiveness to changes in their
environment(pH , temperature) make them very
useful in formulating different delivery systems.

In various dosage forms

transdermals
suppositories and pessaries etc.

Conclusion :Hydrogels have become a

important &
vital requirement in advanced drug delivery
systems.

Hydrogels: Swelling
Upon preparation the hydrophilic gel is brought in contact
with water to yield the final solvated network structure
Thermodynamics compatibility favor the interaction of
macromolecular chains solvent molecules
Thus; the network expands
The thermodynamically driven swelling force is
counterbalanced by the retractive force of the crosslinked
structure
Two forces become equal at some point and equilibrium
is reached

Hydrogels: Swelling
Degree of swelling can be quantified by:
ratio of sample volume in the swollen state to volume
in the dry state
weight degree of swelling: ratio of the weight of
swollen sample to that of the dry sample
Why is the degree of swelling important?
solute diffusion coefficient through the hydrogel
surface properties and surface mobility
optical properties (particularly for contact lens
applications)
mechanical properties

Hydrogels: Swelling
Highly swollen hydrogels:
cellulose derivatives
poly(vinyl alcohol)
poly(N-vinyl 2-pyrrolidone), PNVP
poly(ethylene glycol)
Moderately or poorly swollen hydrogels:
poly(hydroxyethyl methacrylate), PHEMA and
derivatives
One may copolymerize a higly hydrophilic
monomer with other less hydrophilic monomers
to achieve desired swelling properties

Hydrogels: Applications
Biomedical use due to bio- and blood-compatibility
Pharmaceutical use due to hydrophilicity
(controlled/sustained drug release)
Earliest biomedical application contact lenses
good mechanical stability
favorable refractive index
high oxygen permeability
needs hygienic maintenance
unable to correct for astigmatism
lubricating surface coating
used with catheters, drainage tubes and gloves
non-toxic

Hydrogels: Applications
artificial tendon and cartilage
wound healing dressings (Vigilon, Hydron,
Gelperm)
non-antigenic, flexible wound cover
permeable to water and metabolites
low-strength
artificial kidney membranes
artificial skin
maxillofacial and sexual organ reconstruction
materials
vocal cord replacement

Hydrogels: Applications
Pharmaceutical applications
monomer composition and relative amounts of multi-polymer
hydrogels can be varied to alter the diffusion characteristic and
permeability of the gel containing pharmaceutical agents
Methods for drug delivery
drug gets trapped in the hydrogel during polymerization
drug introduced during swelling in water
Release occurs by outflow of drug from the gel and
inflow of water to the gel
Rate of diffusion is explained by Ficks law:
J = -D dCm/dx
J: flux (g/cm2sec)
D: diffusion coefficient
Cm: concentration of the diffusing material

References :ENCYCLOPEDIA of CDPS Vol-2 , By , Edith Mathiowitz

.
pg.no. 397- 415

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