Presented By:

SANDEEP MOLLIDAIN
M.Pharmacy (pharmaceutical technology)
Dept. of pharmaceutical technology.
Vsp.
 •Introduction
•Classification of Hydrogels
•Advantages of Hydrogels
•Disadvantages of Hydrogels
C •Types of Hydrogels
O •Monomers Used In The Synthesis of Synthetic Hydrogels
•Method of Preparation of Hydrogels
N •Characterization of Hydrogels
T •Common Uses For Hydrogels
E •Pharmaceutical Applications of Hydrogels
•Summary and conclusions
N •References
T •Acknowledgement
S
2
Introduction:

Definition:

 Hydrogel is a network of polymer chains that are

hydrophilic, water insoluble, sometimes found as a

colloidal gel in which water is the dispersion medium.

 Hydrogels are highly absorbent natural or synthetic

polymers.

3
Introduction:

 Hydrogels are crosslinked polymer networks that absorb

substantial amounts of aqueous solutions.

 Hydrogels can contain over 99.9% water.

 Hydrogels are three-dimensional, hydrophilic, polymeric

networks capable of imbibing large amounts of water or

biological fluids.

4
Introduction:

The networks are composed of homopolymers or

copolymers, and are insoluble due to the presence of

chemical crosslinks (tie-points, junctions), or physical

crosslinks, such as entanglements or crystallites.

The high water content of the materials contributes to

their biocompatibility.

5
Introduction:

These crosslinks provide the network structure and

physical integrity.

These hydrogels exhibit a thermodynamic

compatibility with water which allows them to swell in

aqueous media.

6
Classification Of Hydrogels:

7
Advantages of Hydrogels :
Hydrogels possess a degree of flexibility very
similar
to natural tissue, due to their significant water
content.

 Entrapment of microbial cells within Hydrogel

beads has the advantage of low toxicity.

 Environmentally sensitive Hydrogels have the

ability to sense changes of pH, temperature, or the
concentration of metabolite and release their load as

8
result of such a change.
Advantages of Hydrogels:

 Timed release of growth factors and other nutrients

to ensure proper tissue growth.

 Hydrogels have good transport properties.

 Hydrogels are Biocompatible.

 Hydrogels can be injected.

 Hydrogels are easy to modify.

9
Disadvantages of Hydrogels:

Hydrogels are expensive.

 Hydrogels causes sensation felt by movement of the

maggots.

 Hydrogels causes thrombosis at Anastomosis sites.

 The surgical risk associated with the device

implantation and retrieval.

 Hydrogels are non-adherent; they may need to be

secured by a secondary dressing.
10
Disadvantages of Hydrogels:

 Hydrogels used as contact lenses causes lens

deposition,hypoxia, dehydration and red eye

reactions.

 Hydrogels have low mechanical strength

 Difficulty in handling.

 Difficulty in loading.

 Difficulty in Sterilization
11
Types of Hydrogels :

Natural Polymers

e.g.: Dextran, Chitosan, Collagen, Dextran Sulfate

 Disadvantages:

Low mechanical Strength.

Batch variation.

Animal derived materials may pass on viruses.

12
Types of Hydrogels :

Synthetic Polymers

e.g.:Poly (vinyl alcohol)

 Disadvantages:

 Low biodegradability

 Can include toxic substances

13
Classification Of Hydrogel Based Systems:

 Hydrogels can be used in different types of

controlled release systems.

 These are classified according to the mechanism

controlling the release of drug from the device as

- Diffusion controlled systems.

- Swelling controlled system.
- Chemically controlled system.
- Environmental responsive systems.

14
Diffusion Controlled Release Systems:

 Diffusion is the most common mechanism

controlling release.

 In hydrogel based drug delivery system.

There two types :
-Reservoir devices.
-Matrices devices

15
Diffusion Controlled Release Systems:

Reservoir devices:

 They consists of polymeric membrane

surrounding a core containing a drug .

Typically reservoir devices are capsules, cylinders,

slabs or spheres.

Rate limiting step for drug release is diffusion

through the outer membrane of the device.

16
Diffusion Controlled Release Systems:

Draw backs:

In the event that the outer membrane ruptures the

entire content of the device are delivered
instantaneously .

While preparing these device care must taken to

ensure that the device doesn't contain pin holes or
defects that may lead to rupture.

17
Diffusion Controlled Release Systems:

Matrix devices:

In matrix devices the drug is dispersed through out

the 3D structure of the hydrogel.

Release occur due to diffusion of the drug through

out the macro molecular mesh or water filled pores.

18
Swelling Controlled Release Systems:

 In these release drug systems the drug is dispersed

within a glassy polymer .

 Up on contact with biological fluid, the polymer

begins to swell.

 As the penetrant enters the glassy polymer, the

glass transition temperature of the polymer is
lowered allowing for relaxations of the macro
molecular chains.

19
Chemically Controlled Release Systems

They are of two types:

Erodible drug delivery system

-In erodible system drug release occurs due to
degradation or dissolution of the hydrogel.

Pendent chain system

-In pendent chain system drug is affixed to the
polymer back bone through degradable
linkages.
-As these linkages degrade drug is released
20
Erodible Drug Delivery System

 It is also known as degradable or absorbable release

system, can be either matrix or reservoir type.

 In reservoir type devices the membrane erodes

significantly and drug is released by diffusion
mechanism.

 Zero order release can be obtained by this system.

21
Pendent Chain System

This system consists of linear homo/co-polymers

with drug attached to the back bone chains.

The drug is released from the polymer by hydrolysis

or enzymatic degradation of these linkages.

22
Stimuli-sensitive Swelling-controlled Release
Systems

Environmentally-sensitive hydrogels have the

ability

to respond to changes in their external environment.

They exhibit dramatic changes in their swelling

behavior, network structure, permeability or

mechanical strength in response to changes in the

pH or ionic strength of the surrounding biological

fluid, or temperature. 23
Stimuli-sensitive Swelling-controlled Release
Systems

Other hydrogels have the ability to respond to

applied electrical or magnetic fields, or to changes

in the concentration of glucose.

Because of their nature, these materials can be used

in a wide variety of applications, such as separation

membranes, biosensors, artificial muscles, chemical

valves and drug delivery devices.

24
pH-Sensitive Hydrogels:

Hydrogels exhibiting pH-dependent swelling

behavior contain ionic networks contain either

acidic or basic groups.

In aqueous media of appropriate pH and ionic

strength, these groups ionize, and develop fixed

charges on the gel.

25
pH-Sensitive Hydrogels:

As a result of the electrostatic repulsions, the

uptake of solvent in the network is increased.

Ionic groups, such as carboxylic or sulfonic acid,

show sudden or gradual changes in their dynamic

and equilibrium swelling behavior as a result of

changing the external pH.

26
pH-Sensitive Hydrogels:
 In these gels, ionization occurs when the pH of the

environment is above the pKa of the ionizable group.

As the degree of ionization increases (increased

system pH), the number of fixed charges increases,

resulting in increased electrostatic repulsions between

the chains.

This, in turn, results in an increased hydrophilicity of

the network, and greater swelling ratios. 27

pH-Sensitive Hydrogels:

 Conversely, cationic materials contain groups such

as amines.

 These groups ionize in media which are at a pH

below the pKb of the ionizable species.

 Thus, in a low pH environment, ionization

increases, causing increased electrostatic repulsions.

The hydrogel becomes increasingly hydrophilic and

will swell to an increased level.

28
Temperature-sensitive Hydrogels:

Temperature-sensitive hydrogels have gained

considerable attention due to the ability of the
hydrogels to swell or deswell as a result of
changing the temperature of the surrounding fluid.

 Widely used in on±off drug release regulations,

biosensors and intelligent cell culture dishes.

29
Temperature-sensitive Hydrogels:

 Thermosensitive hydrogels can be classified as

positive or negative temperature-sensitive systems.

 A positive temperature-sensitive hydrogel has an

upper critical solution temperature (UCST).

 Such hydrogels contract upon cooling below the

UCST.
30
Temperature-sensitive Hydrogels:

Negative temperature-sensitive hydrogels

have a lower critical solution temperature (LCST).

These hydrogels contract upon heating above the

LCST.

31
Other Stimuli-sensitive Hydrogels:

 Several stimuli, other than pH and temperature, can

trigger drug release from a depot.

 These include physical stimuli, such as light,

magnetic field , electric current and ultrasound ,

which can be applied to the systems externally.

 Chemical stimuli, like ionic species , certain

chemical substances and biological compounds.

32
Monomers Used In The Synthesis Of Synthetic
Hydrogels:
Monomer Monomer
abbreviation

HEMA Hydroxyethyl methacrylate

HEEMA Hydroxyethoxyethyl methacrylate

HDEEMA Hydroxydiethoxyethyl methacrylate

MEMA Methoxyethyl methacrylate

MEEMA Methoxyethoxyethyl methacrylate

33
Monomers Used In The Synthesis Of Synthetic
Hydrogels:
Monomer Monomer
abbreviation

EG Ethylene glycol

EGDMA Ethylene glycol dimethacrylate

NVP N-vinyl-2-pyrrolidone

AA Acrylic acid

PEGMA PEG methacrylate

34
Method Of Preparation Of Hydrogels:

Crosslinking

Isostatic Ultra High Pressure

Nucleophilic Substitution Reaction

Using Gelling Agents

Use Of Irradiation

Freeze Thawing 35
Crosslinking:

Linear polymers

Irradiation Chemical compounds

Crosslinking

Monomers used in the preparation of the

ionic polymer network contain an ionizable
group, gets ionized, or undergoes substitution
after the polymerization is completed.
36
By using Cross Linkers:

 To impart sufficient mechanical

Purpose strength to these polymers

 Glutaraldehyde, Calcium chloride

Examples

 Cross linkers prevent burst release of

Advantage the medicaments.

Drawbacks Presence of residue.

37
sostatic Ultra High Pressure :

Suspension of natural biopolymers (starch)

ultrahigh pressure of
5or 20 min
300-700 MPa

gelatinization of starch molecules occur.

IUHP brings about changes in the morphology of

the polymer.
Where as heat-induced gelatinization (40 to 52°C)
causes a change in ordered state of polymer.

38
Nucleophilic Substitution Reaction:

Methacyloyl chloride 2-dimethylamino ethylamine.

Nucleophilic substitution.

N-2-dimethyl amino ethyl-methacryalmide (DMAEMA)

(a pH and temperature sensitive.)

39
By Using Gelling Agents:

Glycophosphate.
 1-2 Propanediol.
Examples Glycerol.
Mannitol.

 Turbidity.
 Presence of negative charged
Drawbacks moieties pose problem of interaction
with the drug.

40
Use Of Irradiation:

 Irradiation method is convenient.

 Hydrogels prepared by microwave
Advantages irradiation are more porous than
conventional methods.

Irradiation method processing is costly

Mechanical strength of such Hydrogels
Drawbacks is less.

41
Freeze Thawing:

 Sufficient mechanical strength.

Advantage  Good Stability.

 Opaque in appearance

Drawbacks  Little swelling capacity.

42
Characterization Of Hydrogels:

43
Atomic Force Microscopy (AFM):

A Multimode Atomic Force Microscope form Digital

Instrument is used to study the surface morphology of
the hydrogels.

44
Atomic Force Microscope
X-ray Diffraction:

Used to understand whether the polymers retain their

crystalline structure or they get deformed during the
pressurization process

45
FTIR (Fourier Transform Infrared Spectroscopy)

Any change in the morphology of

Hydrogels changes their IR absorption
spectra.

Formation of coil or helix which is

indicative of cross linking is evident by
appearance of bands near 1648 cm-1

FTIR
46
Rheology:

Hydrogels are evaluated for

viscosity under constant temperature
(4°C) by using Cone Plate viscometer.

Cone plate viscometer

47
Swelling Behavior:

The Hydrogels are allowed to immerse in aqueous

medium or medium of specific pH to know their

swellability. of these polymeric networks.

These polymers show increase in dimensions related

to swelling.

48
Swelling Behavior:

Swelling degrees (SDs) of hydrogels were measured

at 370 C. The fresh made samples (wet) were weighted

and immersed in buffer solutions with different pH

values. These samples were gently wiped with filter

paper to remove the surface solution when taken out

from the solutions, then weighted and returned to the

Same container at pre-determined time intervals.

49
Swelling Behavior:

The SD was calculated as follows:

SD (%)= (Wt/Wo)×100

W0 = Weight of the original Hydrogel

Wt = is the weight of hydrogel at various swelling times

50
Picture of a swollen Hydrogel
In-vitro Release Study For Drugs:

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

51
In-vitro Release Study For Drugs:

Dissolution media:
Buffer solution with various pH
values.

R.P.M: 90 rpm.

Temperature : 370C.

Sink condition is maintained by

replacing the buffer periodically.

Dissolution apparatus

52
Physical, Chemical And Toxicological Properties Of
Hydrogels:

 Factors affecting swelling of hydrogels.

 Mechanical properties.

 Cytotoxicity and in-vivo toxicity.

53
Factors Affecting Swelling Of Hydrogels:

Crosslinking ratio

 It is defined as the ratio of moles of crosslinking

agent to the moles of polymer repeating units.

 The higher the crosslinking ratio, the more

crosslinking agent is incorporated in the hydrogel

structure.
54
Factors Affecting Swelling Of Hydrogels:

Crosslinking ratio
 Highly crosslinked hydrogels have a tighter

structure, and will swell less compared to the

same hydrogels with lower crosslinking ratios.

 Crosslinking hinders the mobility of the

polymer

chain, hence lowering the swelling ratio.

55
Factors Affecting Swelling Of Hydrogels:

Chemical Structure

 The chemical structure of the polymer may also

affect the swelling ratio of the hydrogels.

Hydrogels containing hydrophilic groups swell to a

higher degree compared to those containing

hydrophobic groups..

56
Factors Affecting Swelling Of Hydrogels:

Chemical Structure
Hydrophobic groups collapse in the presence of

water, thus minimizing their exposure to the water

molecule.

As a result, the hydrogels will swell much less

compared to hydrogels containing hydrophilic

groups.
57
Factors Affecting Swelling Of Hydrogels:

Chemical Structure
Swelling of environmentally-sensitive hydrogels

can be affected by specific stimuli.

Swelling of temperature-sensitive hydrogels can

be

affected by changes in the temperature of the

swelling media.

58
Factors Affecting Swelling Of Hydrogels:

Chemical Structure

Ionic strength and pH affect the swelling of ionic

strength- and pH-sensitive Hydrogels, respectively.

There are many other specific stimuli that can affect

the swelling of other environmentally-responsive

Hydrogels.

59
Mechanical properties:

Mechanical properties of hydrogels are very

important for pharmaceutical applications.

The integrity of the drug delivery device during

the lifetime of the application is very important to

obtain FDA approval, unless the device is

designed as a biodegradable system.

60
Mechanical properties:

A drug delivery system designed to protect a

sensitive therapeutic agent,such as protein, must

maintain its integrity to be able to protect the protein

until it is released out of the system.

Changing the degree of crosslinking has been

utilized to achieve the desired mechanical property

of the hydrogel. 61
Mechanical properties:

Increasing the degree of crosslinking of the system

will result in a stronger gel.

However, a higher degree of cross-linking creates a

more brittle structure.

Hence, there is an optimum degree of crosslinking

to achieve a relatively strong and yet elastic

hydrogel.
62
Mechanical properties:

Copolymerization has also been utilized to achieve

the desired mechanical properties of hydrogels.

Incorporating a co-monomer that will contribute

to H-bonding can increase the strength of the

hydrogel.

63
Cytotoxicity And In-vivo Toxicity:

Cell culture methods, also known as cytotoxicity

tests, can be used to evaluate the toxicity of

hydrogels.

Three common assays to evaluate the toxicity of

hydrogels include

-extract dilution.
-direct contact.
-agar diffusion. 64
Cytotoxicity And In-vivo Toxicity:

Most of the problems with toxicity associated with

hydrogel carriers are the unreacted monomers,

oligomers and initiators that leach out during

application.

So, a good understanding the toxicity of the

monomers and initiators used is very important.

65
Cytotoxicity And In-vivo Toxicity:

Approaches to solve this problem:

Modifying the rate of polymerization in order to

achieve a higher conversion

Extensive washing of the resulting hydrogel.

Formation of hydrogels without any initiators to

eliminate the problem of the residual initiator.

66
Cytotoxicity And In-vivo Toxicity:

 Commonly used technique to eliminate the problem

of the residual initiator is by using gamma irradiation.

Hydrogels can be made without the presence of

initiators by using thermal cycle to induce

crystallization. The crystals formed act as physical

crosslinks and are able to absorb the load applied to

the hydrogels.
67
Common Uses For Hydrogels:

68
harmaceutical Applications Of Hydrogels:

Peroral Drug Delivery Subcutaneous Drug Delivery

Drug Delivery In The Oral Cavity Hydrogels To Fix Bone Replacements

Drug Delivery in the G.I.T Tissue Engineering

Ocular Delivery Protein Drug Delivery

Transdermal Delivery Topical Drug Delivery

69
Peroral Drug Delivery:

Drug delivery through the oral route has been the

most common method in the pharmaceutical

applications of hydrogels.

In peroral administration, hydrogels can deliver

drugs to four major specific sites; mouth, stomach,

small intestine and colon.

70
Peroral Drug Delivery:

 By controlling their swelling properties or

bio-adhesive characteristics in the presence of a

biological fluid, hydrogels can be a useful device

for releasing drugs in a controlled manner at these

desired sites.

71
Peroral Drug Delivery:

 Additionally, they can also adhere to certain

specific

regions in the oral pathway, leading to a locally

increased drug concentration, and thus, enhancing

the drug absorption at the release site.

72
Drug Delivery In The Oral Cavity:
 Drug delivery to the oral cavity can have versatile

applications in local treatment of diseases of the

mouth, such as periodontal disease, stomatitis,

fungal and viral infections,and oral cavity cancers.

Long-term adhesion of the drug containing hydrogel

against copious salivary flow, which bathes the oral

cavity mucosa, is required to achieve this local drug

delivery. 73
Drug Delivery in the G.I.T:

Advantages with oral route

 Ease of administration of drugs.

 Availability of large surface area for drug absorption

 High patient compliance.

Drawbacks with oral route

 First pass metabolism.

 Pre-systemic metabolism.

74
Drug Delivery in the G.I.T:
Hydrogel-based devices can be designed to deliver

drugs locally to specific sites in the GI tract.

E.g.,: Specific antibiotic drug delivery systems for the

treatment of H.pylori infection in peptic ulcer disease

These Hydrogels protect the insulin in the harsh, acidic

environment of the stomach before releasing the drug

in the small intestine.

75
Ocular Delivery :

Drawbacks with ocular route

Effective tear drainage; blinking &Low
permeability

of the cornea.

Limited absorption due to rapid elimination leading

to poor ophthalmic bioavailability.

Due to the short retention time, a frequent dosing

regimen is necessary for required therapeutic

76
efficacy.
Ocular Delivery :

Hydrogels in Ocular Delivery

Silicone rubber Hydrogel composite ophthalmic

inserts extended the duration of the Pilocarpine to

10 hr, compared to 3 hr when Pilocarpine nitrate was

dosed as a solution.

77
Ocular Delivery :

Hydrogels in Ocular Delivery

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.

78
Ocular Delivery :

Advantages

Swollen Hydrogels can deliver drugs for long

duration.

 Easy to remove.

Patient compliance is high.

79
Transdermal Delivery :

Purpose

 Drug delivery to the skin has been generally

used to treat skin diseases or for disinfections

of the skin.

 Transdermal route is employed for systemic

delivery of drugs.

80
Transdermal Delivery :

 The possible benefits of transdermal drug delivery

are - drugs can be delivered for a long duration.

- drugs can be delivered at a constant rate.

- drug delivery can be easily interrupted on

demand by simply removing the devices.

- drugs can bypass hepatic first-pass

metabolism.
81
Transdermal Delivery :

 Furthermore, because of their high water content,

swollen hydrogels can provide a better feeling for

the skin in comparison to conventional ointments

and patches.

82
Subcutaneous delivery:

 Subcutaneously inserted exogenous materials may

more or less evoke potentially undesirable body

responses, such as inflammation, carcinogenecity

and immunogenecity.

 Therefore, biocompatibility is a prerequisite that

makes materials implantable.

83
Subcutaneous delivery:

 Due to their high water content, hydrogels are

generally considered as biocompatible materials.

 They also provide several promising properties:

* minimal mechanical irritation upon in-vivo

implantation, due to their soft, elastic

properties.
84
Subcutaneous delivery:
* Prevention of protein adsorption and cell

adhesion arising from the low interfacial

tension between water and hydrogels;

* Broad acceptability for individual drugs with

different hydrophilicities and molecular sizes

* Unique possibilities to manipulate the release

of incorporated drugs by crosslinking density

and swelling. 85
Hydrogels To Fix Bone Replacements:

 Provided orthopedic fasteners and replacements

hip and knee replacements, etc. are coated with

Hydrogels 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.

86
Hydrogels To Fix Bone Replacements:

87
Protein Drug Delivery:

 Interleukins are conventionally given as injection.

 Hydrogels have the following advantages

-Better patient compliance.

-Hydrogels form insitu and release proteins

slowly

-They are biodegradable and biocompatible.

88
Topical Drug Delivery:

Hydrogels are used to deliver drugs like Desonide

(synthetic corticosteroid) usually used as an anti-

inflammatory.

 Hydrogels with their moisturizing properties avoids

scaling and dryness and has better patient

compliance.

89
Topical Drug Delivery:

 Antifungal formulations like Cotrimazole has been

developed as Hydrogel formulation for vaginitis and

shows better absorption than conventional cream

formulations.

90
Tissue Engineering:

Microgels (micronized Hydrogels) can be used to

deliver macromolecules like phagosomes in to

cytoplasm of antigen-presenting cells.

 The release is because of acidic conditions. Hydrogels

mold themselves to the pattern of membranes of the

tissues and have sufficient mechanical strength.

This property is also used in cartilage repairing

91
In The Treatment Lower Extremity Diabetic ulcers:

Diabetic ulcers are the primary cause of amputations

of the leg, foot,or toe.

NanoDOX™

A topical doxycycline Hydrogel for chronic wounds

 NanoDOX™ contains 1% Doxycycline Monohydrate

Hydrogel.

Improve the topical delivery to increase local efficacy

92
Rectal Delivery:

This route has been used to deliver many types of

drugs for treatment of diseases associated with the

rectum, such as hemorrhoids.

ADVANTAGES:

This route is an ideal way to administer drugs

suffering heavy first-pass metabolism.

93
Rectal Delivery:

DRAWBACKS:

 Patients compliance is less due to discomfort

arising from given dosage forms.

Substantial variability in patient’s acceptance of

treatment. this leads to variation of availability of

drugs.

94
Summary & Conclusion:

Recent developments in the field of polymer

science and technology has led to the development

of various stimuli sensitive hydrogels like pH,

temperature sensitive, which are used for the targeted

delivery of proteins to colon, and chemotherapeutic

agents to tumors.

95
Summary & Conclusion:

 Some environmental variables, such as low pH and

elevated temperatures, are found in the body.

 For this reason, either pH-sensitive and/or

temperature sensitive hydrogels can be used for

site-specific controlled drug delivery.

96
Summary & Conclusion:

 Hydrogels that are responsive to specific molecules,

such as glucose or antigens, can be used as

biosensors as well as drug delivery systems.

 The hydrogels may be suitable as a wound

substitutes and can be used in wound healing.

97
Summary & Conclusion:

New synthetic methods have been used to prepare

homo- and co-polymeric hydrogels for a wide

range of drugs, peptides, and protein delivery

applications.

Hydrogels are also used in regenerating

human tissue cells.

98
References:

1.Remington: The Science and Practice of Pharmacy.

Published by Lippincott Williams & Wilkins, 2005.

Twenty-First Editions. P.NO. 294,756,867,868.

2. Handbook of Pharmaceutical Excipients, A. Wade and P.J.

Weller ed., The Pharmaceutical Press, London, 1994, pp.

229–232.

3. British Pharmacopoeia 2002, the Stationary Office,

London, 2002, p. 2092–2094.

99
Thank You

100