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Presented By: SANTOSH THORAT (PE/2012/315) Dept. Of Pharmaceutics 12/4/2012 1 SUPERPORUS HYDROGEL
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Page 1: superporus hydrogel

Presented By: SANTOSH THORAT

(PE/2012/315) Dept. Of Pharmaceutics

12/4/2012 1 SUPERPORUS HYDROGEL

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CONTENTS

Introduction

Formulation

Synthetic steps

Generations of SPHs

SPH characterization

Applications

Conclusions

References

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HYDROGELS:

Three-dimensional networks of hydrophilic polymer chains that do not dissolve but can swell in water.

both solid like and liquid like properties

high biocompatibility

environmental stimuli respondent

(temperature, pH, light, specific molecules) Ideal for controlled drug delivery\

Classification: Based upon Porosity

I. Nonporous

II. Microporous

III. Macroporous

IV. Superporous

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Superporous hydrogels (SPHs)

The fast swelling property is based on water absorption through open porous structure by capillary force.

SWELLING PROPERTIES :

The SPHs swell immediately upon contact with water regardless of their size in the dried state.

The SPHs unique property of size independent fast swelling kinetics of SPHs is accounted for by their interconnected open cellular structure

The open porous structure allows extremely fast absorption of water into the center of the dried matrix by capillary force

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Formulations for SPH Material Role

Acrylamide, Acrylic acid Monomer

Bisacylamide Cross-linker

Deionized water Solvent

Ammonium persulfate Oxidant

Tetramethyl ethylenediamine Reductant

Glacial acetic acid Foaming aid

Sodium bicarbonate Foaming agent

PEO–PPO–PEO block copolymers Foam stabilizer

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H. Omidian et al. / Journal of Controlled Release 102 (2005) 3–12

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Synthetic steps:

Step 1: The monomer is first diluted with certain amount of water to reach a desired monomer concentration.

Step 2: Dilution with water also makes it easy to handle the monomers. For instance, the water-diluted glacial acrylic acid possesses superior handling properties as compared with acrylic acid because of its lower freezing temperature.

Step 3 Addition of a cross-linker.

Step 4: To produce a foam during polymerization , foaming aid such as glacial acetic acid and acrylic acid are added to the monomer solution.

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Steps 5: To promote polymerization, redox couples of ammonium persulfate / sodium metabisulfite or potassium persulfate /sodium metabisulfite and thermal initiators, such as ammonium persulfate or potassium persulfate , are used.

Steps 6 : Since the foam stability is essential for producing homogeneous SPHs, surfactants, such as PEO–PPO–PEO triblock copolymers, are used during the synthesis.

Step 7 : Lastly, to generate gas bubbles, acid-dependent foaming agent, such as sodium bicarbonate is added to the formulation.

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Postsynthesis steps of SPHs.

Dehydration using ethanol: helps to

stabilize the foamed product and prevent

it from shrinking.

Drying

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Generations of SPHs

The first-generation SPHs: Conventional SPHs

Characterized by fast swelling,

High swelling ratio,

Weak mechanical properties.

The second-generation SPHs: SPH composites

Characterized by fast swelling,

Medium swelling ratio

Improved mechanical properties.

The third-generation SPHs: SPH hybrids

possess elastic properties that can be highly useful in the development of gastrointestinal devices

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Structural, swelling and mechanical

properties of various SPH generations

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H. Omidian et al. / Journal of Controlled Release 102 (2005) 3–12

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The first-generation SPHs:

Conventional SPHs

In 1999, Chen et al prepared SPHs with fast

swelling kinetics and superabsorbent properties for the first time.

The dried SPHs swell fast to a large size, larger than a few hundred times.

Difficult to handle without breaking.

The CSPHs are fragile against bending or tensile stresses.

The lack of desirable mechanical properties of the conventional SPHs triggered the development of the second-generation SPH composites.

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Hossein Omidian et al,JPP 2007, 59: 317–327

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The second-generation SPHs:

SPH composites

A matrix-swelling additive or a composite

agent is utilized.

As the cross-linking polymerization proceeds throughout the solution, individual swollen composite agent particles are connected together through polymer chains connecting them.

The presence of composite agent in SPH composites results in improved mechanical properties over conventional

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The third-generation SPHs:

SPH hybrids

a water-soluble counterpart (hybrid agent e.g.

Sodium alginate, sodium carboxymethyl cellulose

and chitosan) is employed with the third

generation SPH formulations.

Integrated semi-interpenetrating network will

be formed first.

Ethylenebisacrylamide has been utilized as a

thermally resistant chemical crosslinker.

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SPH characterization

Surface Morphology:

SEM

Porosity:

Mercury porositometer.

Thermal properties:

13C nuclear magnetic resonance (NMR) and

differential scanning calorimetry (DSC).

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Swelling:

swelling and mechanical properties are generally sensitive to the type and nature of the swelling medium (Ionic strength,pH, salts, organic solvents and pressure).

Where, Ms and Md are the weight of the hydrogel in the

swollen and dried states

Measured gravimetrically and volumetrically

swelling parameters can be evaluated at low (room temperature) or medium/ high temperatures (body fluid temperature of 37°C)

Tcore -The Tcore identifies the opaque/transparent transition in SPHs.

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Mechanical properties:

Regular mechanical testers and texture

analysers are commonly used to evaluate

SPH mechanical properties.

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Gastric simulator:

The simulator measures the amount of

energy absorbed by the sample until it fails

under certain stresses

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Safety/toxicity:

Clinical observations, clinical pathology,

chemistry and haematology, ethylene glycol

and glycolic acid were monitored during this

study.

Induction of emesis within approximately

45min to 2 h post-dose did not cause any

safety concerns such as oesophageal

obstruction

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PHARMACEUTICAL

APPLICATIONS

1. Development of gastric retention devices

2. Development of fast-dissolving tablets

3. Development of diet aid

4. SPH-based gastroretentive platforms

5. Chemoembolization and occlusion devices

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DEVELOPMENT OF GASTRIC

RETENTION DEVICES

The idea was to make an oral formulation to

swell fast to a size large enough to prevent

them from passing through the pylorus.

Maximum swelling should in about 20 minutes

because water is known to remain in the

stomach for about 30 minutes

e.g. Superporous Hydrogels for Metoprolol

Tartrate as a Gastro Retentive System

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DEVELOPMENT OF PERORAL

PEPTIDE DELIVERY SYSTEMS

Superporous hydrogels and their composites that increase their volume by about 200-fold.

Such volume increase allowed the gels to mechanically stick to the intestinal gut wall and deliver the incorporated drug directly to the gut wall.

e.g. buserelin, octreotide and insulin

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DEVELOPMENT OF FAST- DISSOLVING TABLETS

By the direct compression method is to add fine particles of superporous hydrogels to the drug and other excipients.

Superporous hydrogel microparticles possess open pore structures

This unique porous structure allows for transport of water through capillary forces.

Yang et al (2004) used poly (acrylic acid)-based SPH microparticles to make fast-melting tablets of ketoprofen. The tablets could swell to about 80 and 50 times in distilled water and 0.2 M phosphate

buffer, respectively.

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DEVELOPMENT OF DIET AID

Superporous hydrogel tablets so that the

swollen superporous hydrogels can occupy a

significant portion of the stomach space,

leaving less space for food.

The presence of a bulky gel or gels in the

stomach is expected to suppress the

appetite.

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SPH-BASED GASTRORETENTIVE PLATFORMS

Requirements for a swellable gastroretentive platform were found to be swelling rate (within minutes), swelling capacity (preferably 8– 15% v/v), shape, mechanical strength (resist pressures in the range 0.5–2.0 N cm−2, preferably in the fed state), flexibility, a controlled disintegration, ease of drug loading, stability and pharmaceutical acceptability.

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CHEMOEMBOLIZATION:

Embolization has been used for cancer

treatment by restricting the oxygen supply

to the growing tumours.

A chemotherapeutic agent and an anti-

angiogenic agent could be loaded into SPHs

for chemoembolization therapy.

They fit better in the blood vessels and

provide better blocking.

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Non-pharmaceutical Applications

Superporous hydrogels are also useful in the

development of simple tools for prevention

of water leakage.

They can also be used for preventing water

spill around water-sensitive materials.

Superporous hydrogels are useful for

making toys that can change their sizes and

colors extremely fast.

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Conclusions

Superporous hydrogels are a new class of hydrogel materials that, regardless of their original size, rapidly swell to a large size.

Different generations of SPHs evolved to address the needs for certain pharmaceutical applications.

Various pharmaceutical and biomedical applications of superporous hydrogels have been made, and several products are under development.

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References

Hossein Omidian, Jose G. Rocca, Kinam Park,” ReviewAdvances in superporous hydrogels” Journal of Controlled Release 102 (2005) 3 –12.

Assadang Polnok , J. Coos Verhoef ,Gerrit Borchard,Narong Sarisuta, Hans E. Junginger,” In vitro evaluation of intestinal absorption of desmopressin using drug-delivery systems based on superporous hydrogels” International Journal of Pharmaceutics 269 (2004) 303–310.

Jia Kuang, Kun Young Yuk, Kang Moo Huh,” Polysaccharide-based superporous hydrogels with fast swelling and superabsorbent properties”, Carbohydrate Polymers 83 (2011) 284–290.

Cui Tang , Chunhua Yin , Yuanying Pei , Min Zhang , Lifang Wu, ” New superporous hydrogels composites based on aqueous Carbopol solution (SPHCcs): synthesis, characterization and in vitro bioadhesive force studies”, European Polymer Journal 41 (2005) 557–562.

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Dukjoon Kima, Kinam Park,” Swelling and mechanical properties of superporous hydrogels of poly(acrylamide-co-acrylic acid)/polyethylenimine interpenetrating polymer networks”, Polymer 45 (2004) 189–196.

Jun Chen, Kinam Park,” Synthesis and characterization of superporous hydrogel

composites”, Journal of Controlled Release 65 (2000) 73–82.

Hossein Omidian, Kinam Park and Jose G. Rocca,” Recent developments in superporous hydrogels” JPP 2007, 59: 317–327.

N Vishal Gupta , HG Shivakumar,” Development of a Gastroretentive Drug Delivery System based on Superporous Hydrogel”, Tropical Journal of Pharmaceutical Research June 2010; 9 (3): 257-264.

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