Hydrogels are water-swollen polymer networks that can absorb large amounts of water. They have numerous pharmaceutical and biomedical applications due to their unique bulk and surface properties. Hydrogels can be designed to respond to environmental stimuli like pH, temperature, and ionic strength. This allows for controlled drug release in response to changes in the surrounding conditions. Hydrogels find use in various drug delivery applications like oral, ocular, and subcutaneous delivery due to their biocompatibility and ability to encapsulate and release bioactive compounds.

1. HYDROGEL
By:Rajesh L. Dumpala
(B.Pharm, M. Pharm.) PhD. ( Pursuing)
Research Scientist,
Alembic Research Centre. Vadodara
E.Mail:-rdumpala64@gmail.com

2. Defination: Hydrogels are water swollen
three dimensional structures composed of
primarily hydrophilic polymers. These are
cross linked macro molecular networks that
are insoluble but are able to swell rapidly in
water or biological fluids.

3.  The research on hydrogels is more than four
decades old but there has been a tremendous
growth in the recent past because of their unique
bulk and surface properties.
 They form the basis of many novel drug delivery
systems. Hydrogels can be made to respond to
the environment and the extent of the response
can be controlled. The environmental conditions
to which a hydrogel can be made responsive pH,
temperature, electric field, ionic strength, salt
type, solvent, external stress, light or a
combination of these.
 It is because of these unique properties that
these classes of polymer based systems
embrace numerous pharmaceutical and bio
medical applications.

4.  Hydrogel-forming natural polymers include
proteins such as collagen and gelatin, and
polysaccharides such as alginate and
agarose. Synthetic polymers that form
hydrogels are traditionally prepared using
chemical polymerization methods. There
are many approaches based on genetic
engineering and biosynthetic methods to
also create the unique hydrogel materials.

6. ADVANTAGES OF
HYDROGELS
 Biocompatible.
 It can be injected.
 It is easy to modify.
 Timed release of growth factors and other nutrients to
ensure proper tissue growth
 Entrapment of microbial cells within polyurethane
hydrogel beads with the advantage of low toxicity.
 Environmentally sensitive hydrogel have the ability to
sense changes of pH, temperature or the concentration
of metabolite and release their load as result of such a
change.
 Natural hydrogel materials are being investigated for
tissue engineering, which include agarose,
methylcellulose and other naturally derived polymers.

7. DISADVANTAGES OF
HYDROGELS
 The main disadvantage is the high cost.
 Its disadvantage includes surgical risk
associated with the device implantation
and recovery.
 Hydrogels are non-adherent; they may
need to be secured by a secondary
dressing.
 Disadvantages of hydrogel in contact
lenses are lens deposition, hypoxia,
dehydration and red eye reaction.

8. PROPERTIES OF HYDROGELS
 The cross-linking of hydrogels makes their structure insoluble
in water due to ionic interaction and hydrogen bonding.
 Tendency to absorb water or biological fluids in large amount,
at least 10-20 times their molecular weight and become
swollen in response to pH, temperature, electric field, ionic
strength, salt type, solvent, external stress, light or a
combination of these.
 Cross linked hydrogels have sufficient mechanical strength
and physical integrity.
 An ideal material for use in drug delivery and immobilization
of proteins, peptides, and other biological compounds.
 Similar physical properties as that of natural living tissue, due
to high water content, soft, rubbery consistency, low
interfacial tension with water and biological fluids.
 Hydrogels are (swellable polymeric materials) three
dimensional networks of hydrophilic polymers

9. CLASSIFICATION OF
HYDROGELS
 Based on the method of preparation, hydrogels are classified
into:
◦ Homo-polymer hydrogels
◦ Co-polymer hydrogels
◦ Multi polymer hydrogels
 Based on the ionic charges hydrogels can be classified into:
◦ Neutral hydrogels
◦ Anionic hydrogels
◦ Cationic hydrogels
◦ Ampholytic hydrogels
 Based on the structure hydrogels can be classified into:
◦ Amorphous hydrogels
◦ Semi-crystalline hydrogels
◦ Hydrogen bonded hydrogels

10.  Based on the mechanism controlling the drug release
they are classified into:
(A) Diffusion controlled release systems
 Reservoir system
 Matrix system
(B) Swelling controlled release systems
(C) Chemically controlled release systems
• Erodible drug delivery system
• Pendent chain systems
(D) Environment responsive systems
• pH sensitive hydrogel
• Temperature sensitive hydrogel
• Complexing hydrogel
• Sensitive to chemical or enzymatic reaction
• Magnetically responsive systems

11. Mechanism of Stimuli Responsive Hydrogels
STIMULUS HYDROGEL MECHANISM
pH Acidic or basic hydrogel Change in pH→ swelling→
release of drug
Ionic Strength Ionic hydrogel Change in ionic strength→ change
in concentration of ions inside
gel→ change in swelling→ release
of drug
Chemical Species Hydrogel containing electron
accepting groups
Electron donating compound→
formation of charge/transfer
complex→ change in swelling→
release of drug
Enzyme-substrate Hydrogel containing immobilized
enzymes
Substrate present→ enzymatic
conversion→ product changes→
swelling of gel→ release of drug

12. Magnetic Magnetic particles dispersed in
alginate microsphere
Applied magnetic field→ change
in pores in gel→ change in
swelling→ release of drug
Thermal Thermoresponsive hydrogel Change in temperature→ change
in polymer-polymer and water
interaction→ change in
swelling→ release of drug
Electrical Polyelctrolyte hydrogel Applied electric field→
membrane charging→
electrophoresis of charged
drug→ change in swelling→
release of drug
Ultrasound
irradiation
Ethylene-vinyl alcohol hydrogel Ultrasound irradiation→
temperature increase→ release
of drug

13. PREPARATION METHODS OF HYDROGELS
(1)Isostatic Ultra High Pressure (IUHP)
In this method suspension of natural
biopolymers (i.e. starch) is subjected to
ultrahigh pressure of (300-700 Mpa) for 5 to
20 minutes in a chamber which brings about
changes in the morphology of the polymer
(i.e. gelatinization of starch molecule occur).
It is different from heat-induced gelatinization
where a change in ordered state of polymer
occurs.
Usually the temperature within the chamber
varies from 40 to 52̊C.

14. (2)CROSS-LINKING METHODS
(A) Cross-linking of Polymers:
In this method chemically cross-linked gels are
formed by radical polymerization of low molecular
weight monomers or branched homopolymers or
copolymers in the presence of cross-linking agent.
This reaction is mostly carried out in solution for
biomedical applications.
(B) Copolymerization/Cross-linking Reactions:
Copolymerization reactions are used to
produce polymer gels, many hydrogels are
produced in this fashion, for example poly
(hydroxyalkyl methylacrylates).

15. (C)Cross-linking by High Energy Radiation:
High energy radiation, such as gamma and
electron beam radiation can be used to polymerize
unsaturated compounds.
Water soluble polymers derivatized with vinyl
groups can be converted into hydrogels using high
energy radiation.
(D) Cross-linking Using Enzymes:
Recently a new method was published using an
enzyme to synthesize PEG-based hydrogels.
A tetrahydroxy PEG was functionalized with
addition of glutaminyl groups and networks were
formed by addition of transglutaminase into solution
of PEG and poly (lysine-cophenylalanine).

16. (3)Use of Nucleophilic Substitution Reaction
Hydrogel of N-2-dimethylamino ethyl-
methacrylamide (DMAEMA), a pH and
temperature sensitive hydrogel has been
prepared by nucleophilic substitution reaction
between methacyloyl chloride and 2-
dimethylamino ethylamine.
(4) Use of Gelling Agent
Gelling agents like glycophosphate, glycerol,
mannitol etc. have been used in formation of
hydrogels.
Usually the problem of turbidity and presence
of negative charged moieties which are
associated with this method pose problem of
interaction with the drug.

17. (5) Use of Irradiation and Freeze thawing
 Irradiation method is suitable and
convenient but the processing is costly.
The mechanical strength of such
hydrogels is less.
 However, with freeze thawing method,
the hydrogels so formed have sufficient
mechanical strength and stability but are
opaque in appearance with a little
swelling capacity.
 However, hydrogels prepared by
microwave irradiation are more porous
than conventional methods.

18. CHARECTERIZATION OF HYDROGELS
 Morphological Evaluation
◦ This is done by instrument like stereomicroscope.
◦ Also the texture of hydrogel is analyzed by SEM to ensure that
hydrogels, especially of starch, retain their granular structures.
 X-ray Diffraction
◦ It is also used to understand whether the polymers retain their crystalline
structure or they get deformed during the processing pressurization
process.
 FTIR study
◦ Any change in the morphology of hydrogels changes their IR absorption
spectra due to stretching O-H vibration.
◦ Formation of coil or helix which is indicative of cross-linking is evident by
appearance of band near 1648 cm-1.

19.  In Vitro Drug Release Study
◦ Since hydrogels are the swollen polymeric networks,
interior of which is occupied by drug molecules, therefore,
release studies are carried out to understand the
mechanism of release over a period of application.
 Swelling Behavior
◦ The hydrogels are allowed to immerse in aqueous medium
or medium of specific pH to know the swellability of these
polymeric networks.
◦ These polymers show increase in dimensions related to
swelling.
 Rheology
◦ Hydrogels are evaluated for viscosity under constant
temperature of usually 40C by using Cone Plate type
viscometer.

20. APPLICATIONS OF HYDROGELS
 Advances in recombinant protein
technology have identified several
protein and peptide therapeutics for
disease treatment. Thus hydrogels are
primarily used for encapsulation of
bioactive materials and their
subsequent controlled release.
Hydrogel based delivery devices can
be used for oral, ocular, epidermal and
subcutaneous application. These
applications are discussed in detail
below:

21. (1) Drug Delivery in the GI Tract
◦ The ease of administration of drugs and the large surface
area for absorption makes the GI tract most popular route
for drug delivery. It is however, also a very complex route,
so that versatile approaches are needed to deliver drugs for
effective therapy.
◦ Hydrogel-based devices can be designed to deliver drugs
locally to specific sites in the GI tract. Specific antibiotic
drug delivery systems for the treatment of Helicobacter
pylori infection in peptic ulcer disease.
◦ These hydrogels protect the insulin in the acidic
environment of the stomach before releasing the drug in the
small intestine.
◦ Several hydrogels are currently being investigated as
potential devices for colon-specific drug delivery. They are
designed to be highly swollen or degraded in the presence
of colonic enzymes or micro flora, providing colon-
specificity in drug delivery.

22. (2) Rectal Delivery
◦ This route has been used to deliver many types of drugs for
treatment of diseases associated with the rectum, such as
hemorrhoids. This route is an ideal way to administer drugs
suffering heavy first-pass metabolism.
◦ There are however, some drawbacks associated with rectal
delivery. For example, due to discomfort arising from given
dosage forms, there is substantial variability in patient’s
acceptance of treatment. This leads to variation of availability of
drugs, especially those that undergo extensive first-pass
elimination.
◦ Hydrogels offer a way in which to overcome these limitations,
provided that the hydrogels show bioadhesive properties. .
◦ An indomethacin poly vinyl alcohol (PVA) hydrogel used for rectal
administration. Rectal administration of indomethacin hydrogels
to rats yielded high indomethacin plasma concentrations, without
producing a sharp peak, and a sustained-release effect.
◦ Another important issue in rectal drug delivery is to avoid rectal
irritation. The products discussed above, indicated no such
mucosal irritation after drug administration.

23. (3) Ocular drug delivery to the eye is difficult
due to its protective mechanisms, such as effective
tear drainage, blinking, and low permeability of the
cornea.
◦ Thus, eye drops containing drug solution tends to
be eliminated rapidly from the eye and the drugs
show limited absorption, leading to poor
ophthalmic bioavailability. Due to the short
retention time, a frequent dosing regimen is
necessary for required therapeutic efficacy.
◦ This system extended the duration of the
pilocarpine to 10 hr, compared to 3 hr when
pilocarpine nitrate was dosed as a solution.
◦ In-situ forming hydrogels are attractive as an
ocular drug delivery system because of their
facility in dosing as a liquid, and long term
retention property as a gel after dosing.

24. (4) Wound Healing
◦ A modified polysaccharide that occurs in
cartilage has been used in formation of
hydrogels to treat cartilage defects has been
developed.
◦ Honey hydrogels have been used for prompt
wound healing. These hydrogels have matrix
in which honey is cross-linked and most
acceptable, easily peeled and transparent
system.
◦ The hydrogel of gelatin and PVA (polyvinyl
alcohol) along with blood coagulant have been
formulated. The cell adhesive hydrogel
ensured better effect than corresponding gel or
ointment in controlling blood coagulation.

25. (5) Topical drug delivery
◦ Hydrogels are having better patient
compliance than conventional creams.
◦ These hydrogels have moisturizing properties
therefore scaling and dryness is not expected
with this drug delivery system.
◦ Antifungal formulations like cotrimazole have
been developed as hydrogel formulation for
vaginitis. It has shown better absorption than
conventional cream formulations.

26. (6) Cosmetology
◦ For aesthetic (visual) purpose, hydrogels have
been implanted into breast to accumulate them.
◦ These hydrogels swell in vivo in aqueous
environment and retain water. These breast
implants have silicone elastomer shell and are
filled with hydroxyl propyl cellulose polysaccharide
gel.
(7) Protein drug delivery
◦ Interleukins which are conventionally given as
injection are now given as hydrogels. These
hydrogels have shown better patient compliance.
◦ The hydrogel form in situ polymeric network and
release proteins slowly. These are biodegradable
and biocompatible also.

27. (8) Industrial Applicability
Hydrogels have been used as absorbents for industrial effluents
like methylene blue dye. The other example is the adsorption of
dioxins by hydrogel beads.
The DNA of Salmon milt adsorbs dioxins which produce health
hazards like carcinogenicity, immunotoxicity or endocrine disruption.
(9) Application of Hydrogels to Fix Bone Replacements
 Fix bone replacements provided are orthopedic fasteners and
replacements such as nails, screws, pins and knee replacements,
etc., coated with hydrogels and other biocompatible/biodegradable
materials which expand in the presence of liquids.
 Swelling of such coatings causes the fastener or replacement to be
securely fixed into position once inserted into bone material.
 Useful coating materials include methacrylate, hyaluronic acid
esters, and crosslinked esters of hyaluronic acid resulting from the
esterification of hyaluronic acid with polyhydric alcohols. Also
provided is a method for fixing a bone or bone replacement in
position employing such coated orthopedic fasteners or
replacement.

28. (10) Hydrogel for Repairing, Regenerating Human Tissue
 Regenerating healthy tissue in a cancer-ridden liver, healing a biopsy site
and providing wounded soldiers in battle with pain-killing, infection fighting
medical treatment are among the numerous uses the scientists predict for
the new technology.
 Formulating hydrogels as delivery vehicles for cells extends the uses of
these biopolymers far beyond soft-contact lenses into an intriguing realm
once viewed as the domain of science fiction, including growing bones and
organs to replace those that are diseased or injured.
 Hydrogels are formed from networks of super-absorbent, chain-like
polymers. Although they are not soluble in water, they soak up large
amounts of it, and their porous structure allows nutrients and cell wastes to
pass right through them.
(11) Miscellaneous applications
 Hydrogels are also used in other forms of drug delivery like pulsatile drug
delivery or oral drug delivery.
 Injectable hydrogels are also been investigated for cancer drug delivery.
 In situ gel-forming hydrogels for prolonged duration have also been
reported.