Super Porous Hydrogels – Supreme Drug Delivery

 

Venkata Phani Deepthi B.¹*, Varun D.¹, Gopal P.N.V.¹, Babu Rao CH.² and Sumalatha G.¹

¹Hindu college of Pharmacy, Amaravathi Road, Guntur , Andhra Pradesh, India.

²Don Bosco PG College of Pharmacy, Pulladigunta, Guntur Dt, Andhra Pradesh, India.

*Corresponding Author E-mail: deepthibaddula@yahoo.co.in

ABSTRACT:

Gastro retentive drug delivery system is developed mainly for those drugs that are having narrow therapeutic window and are absorbed mainly in the stomach. A number of controlled drug delivery systems are available to increase the gastric residence time of the drug namely  muco adhesive /bio adhesive systems, high density ,magnetic systems, super porous hydrogels, raft systems, low density systems, floating ion exchange resins. Among these super porous hydrogels are one of the most promising drug delivery systems as they swell very fastly  upto 200 times of their own weight. These swollen hydrogels remains in the stomach for prolonged periods and releases the loaded drugs. This unique swelling property allows them to be used as a gastric retention carriers provides sustained release. The present review   mainly focuses on formulation ,preparation  and characterization and applications of super porous hydrogels.

 

KEYWORDS: super porous hydrogels (SPHs), swelling, monomers,  acrylates etc

 

INTRODUCTION:

Hydrogels are crosslinked hydrophilic polymer chains with a network structure consisting of acidic, basic, or neutral monomers, and are able to imbibe large amount of water. The hydrogel swelling properties are mainly relates to the elasticity of the network, the extent of crosslinking, the presence of hydrophilic functional groups (such as -OH, -COOH, -CONH₂, -SO₃H) in the polymer chains, porosity of the polymer¹, manufacturing process, and materials used ² and their swelling takes more time.³ Japanese researchers have created a rapidly self-healing hydrogel material, forming a gel in seconds and useful in regenerative medicine and green chemistry⁴. Nowadays the applications require fast swelling, for that purpose super porous hydrogels were developed.

 

Super porous hydrogels:

A super porous hydrogel (SPH) is a three-dimensional network of a hydrophilic polymer chains and their complete swelling occurs in less than 30 sec. The formulation of super porous hydrogels involves components like cross linking agents, initiators for initiation of polymerization, foaming agents like inorganic carbonates such as Na₂CO₃ and NaHCO₃. These inorganic carbonates are safely used as a gas-forming ingredient in effervescent tablets for antacids.

 

They are safe, cheap, and easy to use.⁵ The formulation of various SPHs were shown in table no-1. ⁶ Mostly vinyl monomers are used for making porous hydrogels and it was shown in  table no-2.⁵ Super porous hydrogels can also be synthesized by using natural xanthan gum.⁷ The property of SPH varies with the type of cross linking agent ⁸ and pH. When the pH  of SPHs  alternating between 1.2 and 7.5 and there was a fast swelling ratio occurs  in a matter of minutes.⁹ There are different  ways to improve swelling behavior of SPHs

 

1.      Some of the vinyl monomers having poor swelling characterstics, so to improve the swelling characterstics of strong poly hydroxyl ethyl methacrylate, different poly(HEMA-coacrylic acid) hydrogels were polymerized and crosslinked,  followed by treating with divalent calcium and trivalent aluminium cations.¹⁰

2.      The swelling power of PEG-grafted SPHs  were  3.6 times faster than the control SPHs and they were prepared by copolymerization of acrylic acid and acrylamide monomers in the presence of PEG acrylate followed by a gas blowing foaming process to create super porous structures.¹¹

3.      By using gamma radiation rapid swelling super porous polyacrylamide hydrogels  were prepared  and  they have very fast swelling kinetics compared to the non-porous hydrogel.¹²

4.      By increasing the pH of the medium, the swelling behaviour of the super porous cross-linked hydrogels containing acrylic-based polymer network showed more swelling.¹³

5.      By using free radical copolymerization,  swelling behavior and biocompatibility of carbopol-containing super porous hydrogel composites having  fast swelling  characterstics.¹⁴

 

There are different ways to improve the mechanical strength

1.      To improve the mechanical strength, several super disintegrants like Ac-Di_sol,Primojel,Explotab and Cross povidone was generally added.¹⁵

 

Swelling and mechanical properties of super porous hydrogels of poly(acrylamide-co-acrylic acid)/ polyethylenimine interpenetrating polymer networks were established.¹⁶

If the super porous hydrogels are very pure they have outstanding swelling properties. Omidian, Hossein et al studied that very-pure super porous hydrogels having outstanding swelling properties.

 

Methods of preparing very pure super porous hydrogels:

They have desirable swelling characteristics and are useful in food and pharmaceutical applications. Such methods include

Ø  Simultaneous use of low and high glass transition monomers to improve purity and swelling profiles of the SPH.

Ø  Use of integration means to prepare very homogenous super porous hydrogel foam.

Ø  Washing the super porous hydrogel in a washing solution comprising different ratios of solvent to non-solvent (e.g., water/alcohol).

Ø  Use of a chemically-induced expansion/contraction process to enhance the efficiency of the multiple washing processes and to fully structuralize the SPH.

Ø  Employing one or more separation techniques, such as rubbing, filtration, centrifugation, compression and cutting to increase the efficiency of the purification process and to enhance the SPH swelling properties.¹⁷

 

Super porous IPN hydrogels were synthesized by using monomers such as poly(acrylamide-co-acrylic acid)/ polyacrylamide. In this PAM is for increasing the swelling ratio and AM oligomer for increasing the compressive strength.¹⁸ The other two methods for controlled drug delivery are ionotropic gelation and poly electrolyte complexation.¹⁹

There are three generations of super porous hydrogels: conventional super porous hydrogels, super porous hydrogel composites, super porous hydrogel hybrids.

 

Generations of Sphs:

First generation SPH (conventional SPHs, CSPHs):

Polymerization and crosslinking of different vinyl monomers in the presence of a foaming agent, a foam stabilizer and a foaming aid resulting in the formation of conventional SPHs having fast swelling kinetics and superabsorbent properties. They are very difficult to handle as they are very rigid and brittle in the dry state. The structural swelling and mechanical properties of various SPH generations are shown in table -3.² The swelling rate of conventional SPHs  was controlled by coating with  a poly (acrylamide-co-acrylic acid) SPH with an ethanolic solution of an amphiphilic block copolymer of ethylene glycol and tetramethylene oxide (PEGTMO).

 

Second generation SPH (SPH composite, SPHCs):

SPH composites involves monomer, crosslinker and initiating system, water-soluble foaming additives but  additionally a swellable filler act as an isolated individual reactor, in which polymerization and crosslinking could occur simultaneously. The swollen particles would then be connected to each other through the extended polymeric chains. Upon drying, an interpenetrated network structure (IPN) would be formed.⁶ Super porous hydrogel composites (SPHCs) based on, carbopol  and o-carboxymethyl chitosan , as the second generation of  SPHs, resulted in improvement of the properties of SPH.²⁰

 

Third generation SPH (SPH hybrids):

In this SPHs contain a crosslinked hydrophilic polymer as swellable filler, a water-soluble counterpart (hybrid agent). An integrated semi-interpenetrating network will be formed upon treating the hybrid agent. Each hybrid agent may require specific treatment. Depending on the agent type and its associated treatment, various third generation SPHs can be created, ranging from high modulus to highly elastic and rubbery (in their water-swollen states). Sodium alginate, sodium carboxymethyl cellulose and chitosan were found to be the most appropriate hydrocolloids with outstanding ionogelation properties.⁶ The super porous hydrogel hybrids  composed of polyacrylamide and sodium alginate have elastic as well as rubbery property in water swollen .²¹

 

Preparation of super porous hydrogels:

Gas blowing/foaming method:

Porous hydrogel is formed by crosslinking polymerization of vinyl monomers thereby producing gas bubbles. Figure 1 shows a process of making a superporous hydrogel.  In a test tube, monomer, initiator and crosslinker are added (Figure 1A). The monomer solution is made slightly acidic to retard the polymerization process.  Addition of sodium bicarbonate generate carbon dioxide bubbles making the foam to rise (Figure 1B). The addition of sodium bicarbonate increases the pH, resulting in faster polymerization of vinyl monomers. Completion of polymerization while the foam is still stable results in formation of super porous hydrogels (Figure 1C).  The three-dimensional structure of super porous hydrogels   of any shape can be easily made and they can be synthesized in any moulds.

 

The size of pores produced by the gas blowing (or foaming) method is in the order of 100 mm and larger. Macroporous hydrogels possess pores in the size range of 100 nm to 10 mm range; the new porous hydrogels were named super porous hydrogels.³

 

 

Table-1 : General features of SPH generations. ⁶

Formulation	CSPH	SPHC	SPHH
1. Monomer; acrylic acid(AAc),salts and esters; acrylamide (AAm)	√	√	√
2. Cross linker	Diacrylate,bisAAm	Diacrylate,bisAAm	Higher MW acrylates
3.Solvent : water	√	√	√
4.Foaming agent: bicarbonates	√	√	√
5.Foaming aid: organic and inorganic acids	AAc;acetic acid;hydrochloric acid	AAc;acetic acid	AAc;acetic acid;citric acid
6.Foam stabilizer: PEO-PPO block co polymers	√	√	√
7. Property modifier: a material used to enhance mechanical properties;these include cross linked and non cross linked hydrophilic natural and synthetic polymers.	None	Super disintegrants including cross linked CMC;poly vinyl pyrrolidone and starch glycolate	Water soluble CMC,alginate, Chitosan,poly vinyl alcohol
8.Initiator	Per sufate/diamine; Water soluble azo	Per sufate/diamine	Per sufate/diamine
9.Post synthesis other than purification/drying	No	No	Physical or chemical cross linking
10.Swelling capacity	100-300 gg-1	100-300 gg-1	upto  50gg-1
11.Swelling rate	5-30s	5-30s	5s to a few min
12.Mechanical properties	No mechanical Strength	resists upto2N cm-2	Resists upto20-100N cm-2
13.Treating agent	No	No	Ion:calcium, Aluminium, Phosphate, Copper.
14.water washing ability	Impractical because of high swelling in water	Very difficult because of high swelling in water.	Readily possible because of high strength and low swelling.
15.Dehydration	Alcohol	Alcohol	Alcohol
16.Drying	Forced and vacuum	Forced/vacuum  and freeze drying	Forced/vacuum and freeze drying
17.Physical appearance in dried state	Rigid brittle	Rigid brittle	Rigid brittle
18.Application	General when high and fast swelling but no mechanical properties are required.	Peroral intestinal absorption of peptides; super disintegrants	Orally administrable swellable drug delivery system gastric retention;bio medical.
19.Characterization	Fast swelling, high swelling and weak mechanical properties;moisture induced plasticization;fragile against bending compression and tensile stresses.	Fast swelling, medium swelling ratio and improved mechanical properties; Moisture induced plasticization; Higher modulus net works fail under brittle fracture mechanism.	Fast swelling, medium swelling and very  high mechanical Properties; Moisture induced Plasticization; Highly elastic in swollen state;very resistant against different stresses; ductile fracture mode

 

Mechanical blowing method:

For large-scale production of super porous hydrogels, mechanical blowing through one or more atomizers may be a better choice than the chemical blowing method. This is because it may not be desirable to complete a polymerization in a few minutes since the heat generated during polymerization may not be dissipated quickly. Thus, a smaller amount of initiator may be used to delay the gelling time (e.g., more than 10 minutes). Since mechanical blowing can start at any time for any duration, the foaming process may begin at the desired time and foam height can be maintained as necessary.  Accurate timing control is possible by mechanical blowing in the large-scale production of super porous hydrogels .²²

 

Drug loading:

In this the amount of buffer required for complete swelling of the super porous hydrogels was determined. The super porous hydrogel was dipped in drug solution and left until all the drug solution was sucked up. The completely drug loaded swollen gel was dried in an oven at 30^oc for overnight.²³ Super porous hydrogels are used for encapsulating various drug molecules, polysacchrarides (starch) , sucrose , cells  etc . The synthesis of fast-swelling starch based SPHs²⁴ and sucrogels (super porous sucrose hydrogels) was done by modifying one or more double bonds in sucrose followed by polymerization resulting in cross linking net work.²⁵  Super porous hydrogel with cells encapsulated were prepared by combining cells with a hydrogel precursor solution and adding a foaming agent.²⁶

 

Characterization of super porous hydrogels:

Swelling studies:

Initially the weight of a completely dried super porous hydrogel was taken and then immersed in excess of swelling medium. The weight of super porous hydrogel at various time intervals after blotting excess of water on the surface was determined. The swelling ratio is given by

Q =  (M_s –M_d)/ M_d

 

Where, Q is the swelling ratio, M_s the mass in the swollen state and M_d the mass in the dried state.

Table-2 : Vinyl monomers used for making porous hydrogels. ⁵

 

Figure -1 :  Formation of  super porous hydrogels

 

Porosity measurement:

The solvent replacement method was used for porosity measurement. Dried hydrogels were immersed overnight in absolute ethanol and weighed after excess ethanol on the surface was blotted. The porosity was calculated from the following equation:

Porosity = (M₂ – M₁) / ρV

where M₁ and M₂ are the mass of the hydrogel before and after immersion in absolute ethanol, respectively; ρ is the density of absolute ethanol and V is the volume of the hydrogel

 

Table-3 : Structural swelling and mechanical properties of various SPH generations. ²

 

 

Determination of void fraction:

The void fraction was calculated by the following equation:

Void Fraction = Dimensional volume of the hydrogel / Total volume of pores

The void fraction inside super porous hydrogels was determined by immersing the hydrogels in HCl solution (pH 1.2) up to equilibrium swelling.  By using these data, the dimensions of the swollen hydrogels, sample volumes were determined.The difference between the weight of the swollen hydrogel  and the weight of  dried hydrogel gives the  the amount of buffer  absorbed into the hydrogels  and it indicates the total volume of  pores in the hydrogels.

 

Water retention:

The water retention capacity (WR_t) as a function of time was determined by using the following equation

WR_t = (W_p - W_d) / (W_s - W_d)

Where W_d is the weight of the dried hydrogel, W_s is the weight of the fully swollen hydrogel, and W_p is the weight of the hydrogel at various exposure times.

 

Mechanical Properties:

Bench comparator  was used to determine the compressive strengths of various super porous hydrogel formulations. The fully swollen hydrogel was put longitudinally under the lower touch of a bench comparator, different scale loads were successively applied on the upper touch  and the point at which the super porous hydrogels completely fractured was determined. The pressure at this point  called penetration pressure (PP) was calculated by the following equation:

PP = F_u/S

Where F_u is the ultimate compressive force at complete breakage of polymer and S is the contact area of the lower touch .

 

Determination of drug content:

A weight of super porous hydrogel containing 4 mg of drug mixed with 10 ml hydrochloric acid solution of pH 1.2  made upto  100 ml  in volumetric flask. The mixture was filtered and the filtered solution was analysed for drug content using UV-Vis spectrophotometer.

 

In vitro  drug release studies:

In vitro drug release from the super porous hydrogel was performed by dissolution studies and the dissolution specifications were shown in table -4

Table-4 :Dissolution  Specifications

Apparatus	United States Pharmacopoeia (USP) Dissolution Test
Type	Type 2      (paddle type)
Temperature	37±0.50C
Rotation speed	50 rpm
Buffer  employed	0.1M  pH 1.2  HCl
Volume of dissolution medium	900 ml
Duration of dissolution	6 hrs.
Volume of sample withdrawn	10 ml
Volume of dissolution medium replaced	10ml
Instrument used	UV-Vis spectrophotometer/HPLC

The obtained data were fitted into various release models for determination of n and k values in case of  Korsmeyer-Peppas equation was used  to determine release mechanism.

Other tests like scanning electron microscopy for surface topographic analysis, FTIR, DSC studies for drug polymer compatibility studies etc will be recommended^.23

 

Rheological Characterization:

Rheological characterization of in situ crosslinkable hydrogels formulated from oxidized dextran and N-Carboxyethyl Chitosan were established by performing the study of gelation kinetics.²⁷

 

Applications:

Superabsorbents:

SPHs and SPH composites are  ideal for improving surgical pads for bleeding control and personal hygiene products such as disposable  non leaky diapers²⁸ and sanitary napkins due to the excellent capillary capacity. They are also used as desiccating agents in place of silica gels. Nowadays the powder forms of superabsorbents are available in the market. ⁵

 

Controlled drug delivery:

SPHs and SPH composites are used as gastro retentive drug delivery sytem and they can  stay in the stomach for several hours up to more than 24 hours and releases the drug slowly for prolonged periods of time.²⁹ Peptide drugs like insulin³⁰ can be delivered orally by this method.³¹ It is also useful for  stomach specific delivery of ranitidine hydrochloride³²  and pantoprazole sodium .³³

 

Diet control:

SPH and their composites taken in stomach swell leaving less space for food intake there by suppressing the apetite ^.3 Thus, they could provide an alternative therapy for obesity.⁵

 

Biomedical applications:

In the biomedical area, SPHs and SPH composites can be used to make various biomedical devices, such as artificial pancreas, artificial cornea, and artificial skin, articular cartilage, soft tissue substitutes, cell growth substrates in tissue engineering, burn dressings, surgical augmentation of the female breast, or hemoperfusion in blood detoxification and in the treatment of uremia.⁵ Vascular ingrowth into super porous hydrogels are useful for cell transplantation, tissue engineering and in combination with cell therapies.³⁴ Hydroxyapatite containing super porous hydrogel composites ³⁵ and  novel scaffolds  of poly(2-hydroxyethyl methacrylate) super porous hydrogels are useful  for bone tissue engineering.³⁶

 

Biotechnology area:

Biotechnologically, SPHs are used in the separation of macromolecules and cells from the medium. SPHs and SPH composites are ideal materials for chromatographic supports due to their extremely larger pores.

 

Structural applications:

The low density of SPHs and SPH composites allows applications as a high-strength, light-weight structural material as well as a packaging material. They will be also good as insulators and fillers in structures with energy-sensitive applications.

 

Fast responsive stimuli-sensitive SPHs:

Hydrogels that can change their volume abruptly with small changes in environmental conditions are known as “intelligent” or “smart” hydrogels and they respond to changes in the environmental conditions, such as temperature, pH, solvent, electric field, specific molecules or ions, light, or pressure. Although these smart hydrogels are highly useful in various applications, the typical response time usually ranges from hours to days, and this slow response time sometimes limits the usefulness of the smart hydrogels. By making super porous smart hydrogels, the response time could be reduced to seconds or minutes.⁵

 

Horticulture:

Sangjoon Kim et al studied the polyacrylamide hydrogels  were employed for horticultural applications to ensure soil hydration in horticulture, but they have a minimal effect on crop life and quality.^.37

Fast dissolving tablets:

The fast dissolving tablets were prepared by direct compression method by adding fine particles of super porous hydrogels to the drug and other excipients.³ Yang S et al studied the poly(acrylic acid) superporous hydrogel (SPH) microparticles  were used to decrease disintegration time of fast-disintegrating tablets (FDTs).^.38

 

Other applications:

G. R. Mahdavinia et al studied the synthesis of porous poly(acrylamide) hydrogels using calcium carbonate and its application for slow release of potassium nitrate  by loading of it into hydrogels  was investigated.³⁹ The performance evaluation of disinfectant formulations were done by  using poloxamer-hydrogel biofilm-constructs using poloxamer F127, a di-block co-polymer of polyoxyethylene and polyoxypropylene.⁴⁰ Biocompatible polymer hydrogels are being used in the biomedicine, agriculture, food processing industry and immobilization of enzymes, stimuli-responsive hydrogels are one of the more promising types of polymeric materials.²⁹

 

REFERENCES:

1.       N. Vishal Gupta* and H.G. Shivakumar: pH-sensitive super porous hydrogels composed of methacrylic acid and acrylamide: preparation and properties: Acta Pharmaceutica Sciencia . 52; 2010: 239-246.

2.       Hossein Omidiana, Jose G. Roccaa, Kinam Parkb,* : Advances in super porous hydrogels : Journal of Controlled Release. 102 ;2005: 3 –12.

3.       Dr. Kinam Park :Super porous hydrogels for pharmaceutical and other applications :Drug development and Delivery. 2(5);2002:

4.       Q Wang et al,: Hydrogel self-heals in seconds: Nature, 20 January 2010 (http://www.rsc.org/chemistryworld/News/2010/January/20011003.asp)

5.       Kinam park, Jun chen, Haesun park  : Super porous hydrogel composites : a new generation of hydrogels           with fast swelling kinetics, high swelling ratio, high mechanical strength:     (http://www.scribd.com/doc/31018290/Super-Porous-Hydrogel-Composites-a-New-Generation-of- Hydrogels-With-Fast-Swelling-Kinetics-High-Swelling-Ratio-and-High-Mechanical-Strength)

6.       Hossein Omidian, Kinam Park and Jose G. Rocca : Recent developments in super porous hydrogels : Journal of pharmacy and pharmacology . 59; 2007 : 317–327 ;

7.       Gils PS, Ray D, Sahoo PK. Characterization of xanthan gum-based biodegradable super porous hydrogel: Int    J  .Biol Macromol. 45(4); 2009:  364-71.

8.       HV Chavda¹, CN Patel : Effect of crosslinker concentration on characteristics of super porous hydrogel :International journal of pharmaceutical investigation. 1(1); 2011: 17-21.

9.       Richard a. Gemeinhart, jun chen , haesun park And kinam park : pH-sensitivity of fast responsive super porous hydrogels: J. Biomater. Sci. Polymer Edn,. 11(12);2000: 1371–1380

10.     Hossein omidian , Kinam park, Umadevi kandalam , Jose g. rocca : Swelling and Mechanical Properties of Modified HEMA based Super porous Hydrogels: Journal of bioactive and compatible polymers. 2 ; 2010 : 483-497

11.     Kang Moo Huh , Namjin Baek, Kinam Park : Enhanced Swelling Rate of Poly(ethylene glycol)-Grafted Super porous Hydrogels:Journal of bio active and compatible polymers. 20(3);2005 : 231-243

12.     Sanju Francis , D. Mitra, B.R. Dhanawade, Lalit Varshney and Sunil Sabharwal  ^; Gamma radiation synthesis of rapid swelling super porous polyacrylamidehydrogels  :Radiation Physics and Chemistry. 78(11); 2009 : 951-953

13.     Debajyoti Ray¹, Prafulla Kumar Sahoo², Guru Prasad Mohanta^m  : Designing of super porous cross-linked hydrogels containing acrylic-based polymer network:Asian journal of pharmaceutics. 2(2); 2008 : 123-127

14.     Cui Tang¹Lichen Yin¹,  Jing Yu¹, Chunhua Yin^1,*, Yuanying Pei^2,* :  Swelling behavior and biocompatibility of Carbopol-containing super porous hydrogel composites : Journal of Applied Polymer Science.              104(5); 2007:  2785–2791.

15.     Yong Qiu,¹  and Kinam Park²  : Superporous IPN Hydrogels Having Enhanced Mechanical Properties. AAPS PharmSciTech. 4(4); 2003: 406-412.

16.     Dukjoon Kim  and Kinam Park : Swelling and mechanical properties of super porous hydrogels of poly(acrylamide-co-acrylic acid)/polyethylenimine  interpenetrating polymer networks. Polymer.  45(1);  2004 : 189-196

17.     Hossein Omidian  Cristian Gavrilas  Wenli Han  Ge Li  Jose G. Rocca ; Very-pure super porous hydrogels having outstanding  swelling properties . United States Patent Application  20080206339 :  (http://www.faqs.org/patents/app/20080206339)

18.     Haiyong Ao, Miaoliang Huang, Jihuai Wu, Jianming Lin, Qunwei Tang, Hui Sun : Synthesis and properties of poly(acrylamide-co-acrylic acid)/polyacrylamide super porous IPN hydrogels  Polymers for Advanced    Technologies.  20(12); 2009 :  1044–1049 .

19.     J.S. Patil*, M.V. Kamalapur, S.C. Marapur, D.V. Kadam:  Ionotropic gelation and polyelectrolyte complexation: the novel techniques to design hydrogel particulate sustained, modulated drug delivery     system: a review: Digest Journal of Nanomaterials and Biostructures . 5(1); 2010 : 241 – 248

20.     Hitesh V. Chavda* 1, Chhaganbhai N. Patel: Preparation and Characterization of Swellable Polymer-Based Super porous Hydrogel Composite of Poly (Acrylamide-co-Acrylic Acid): Trends Biomater.Artif.Organs. 24(1);2010 : 83-89.

21.     Hossein Omidian^1,*, Jose G. Rocca¹, Kinam Park  : Elastic, Super porous Hydrogel Hybrids of  Polyacrylamide and Sodium Alginate ; Macromolecular Bioscience.  6(9); 2006 :  703– 710.

22.     Park, Kinam,Chen, Jun ,Park, Haesun :Hydrogel composites and super porous hydrogel composites having fast swelling, high mechanical strength, and superabsorbent properties  :United States Patent 6271278     (http://www.freepatentsonline.com/6271278.html)q

23.     Vishal Gupta N., Shivakumar H.G.  :   Preparation and characterization of super porous hydrogels as gastroretentive drug delivery system for rosiglitazone maleate : DARU. 18(3);2010 :  200-210

24.     Jia Kuang^a, Kun Young Yuk^a and Kang Moo Huh : Polysaccharide-based super porous hydrogels with fast swelling and superabsorbent properties : Carbohydrate Polymers. 83(1); 2011:  284-290.

25.     Chen, J.; Park, K :. Synthesis of fast-swelling, super porous sucrose hydrogels.: Carbohydrate Polymers. 41(3);2000: 259-268.

26.     Richard A. Gemeinhart: Super porous hydrogel with cells encapsulated therein and  method for producing the same; United States Patent Application 20090291115 : (http://www.faqs.org/patents/app/20090291115)

27.     Lihui Weng,¹ Xuming Chen,² and Weiliam Chen^1* : Rheological Characterization of in situ Crosslinkable Hydrogels Formulated from Oxidized Dextran and N-Carboxyethyl Chitosan : Biomacromolecules.   8(4);2007: 1109–1115.

28.     C. H. Yin et al. Super porous Hydrogels: A Swell Solution for Drug Delivery ;J. Appl. Polym. Sci. 2008,           108, 1238  MaterialsViews.com staff published: 2008-02-20

29.     N Vishal Gupta* and HG Shivakumar: Development of a Gastroretentive Drug Delivery System based on Super porous Hydrogel: Tropical Journal of Pharmaceutical Research . 9 (3);2010: 257-264

30.     Yin L, Ding J, Zhang J, He C, Tang C, Yin C. : Polymer integrity related absorption mechanism of Super porous hydrogel containing interpenetrating polymer networks for oral delivery of insulin.Biomaterials.  31(12);2010 :3347-56.

31.     Swarnali  : Peroral Delivery Of Peptide Through Super porous Hydrogel Review on Fri, 06/27/2008   (http://www.pharmainfo.net/reviews/peroral-delivery-peptide-through-super porous-hydrogel-review)

32.     Hitesh V. Chavda*, Chhaganbhai N. Patel: A newer formulation approach: super porous hydrogel composite-based bioadhesive drug-delivery system: Asian Journal of Pharmaceutical Sciences. 5 (6);2010: 239-250

33.     Gupta NV, Shivakumar HG.: Preparation and characterization of super porous hydrogels as pH-sensitive drug delivery system for Pantoprazole sodium.: Curr Drug Deliv.  6(5);2009: 505-10.

34.     Keskar V, Gandhi M, Gemeinhart EJ, Gemeinhart RA : Initial evaluation of vascular in growth into Super porous hydrogels : J Tissue Eng Regen Med.  3(6);2009: 486-90.

35.     Tolga Demirtaş T, Karakeçili AG, Gümüşderelioğlu M.: Hydroxyapatite containing super porous hydrogel composites: synthesis and in-vitro characterization; J Mater Sci Mater Med.  19(2);2008: 729-35.

36.     Cetin D, Kahraman AS, Gümüşderelioğlu M  : Novel Scaffolds Based on Poly(2-hydroxyethyl methacrylate) Superporous Hydrogels for Bone Tissue Engineering; J Biomater Sci Polym Ed. 2010 Jul 2.

37.     Sangjoon Kim^a; Ganesh Iyer^a; Arunan Nadarajah^a; Jonathan M. Frantz^b; Alison L. Spongberg  : Polyacrylamide Hydrogel Properties for Horticultural Applications: International Journal of Polymer Analysis and Characterization .  15(5); 2010:  307 - 318

38.     Shicheng Yang, Yurong Fu, Seong Hoon Jeong, Kinam Park : Application of poly(acrylic acid) super porous hydrogel microparticles as a super-disintegrant in fast-disintegrating tablets: Journal of Pharmacy and   Pharmacology.  56(4); 2004:  429–436.

39.     G. R. Mahdavinia1*, S. B. Mousavi2, F. Karimi3, G. B. Marandi4, H. Garabaghi1, S. Shahabvand: Synthesis of porous poly(acrylamide) hydrogels using calcium carbonate and its application for slow release of potassium nitrate : eXPRESS Polymer Letters. 3(5); 2009: 279–285

40.     G. Wirtanen¹, S. Salo¹, D.G. Allison^1,2, T. Mattila-Sandholmxy2¹, P. Gilbert  ^.     Performance evaluation of disinfectant formulations using poloxamer-hydrogel biofilm-constructs: Journal of Applied Microbiology.  85(6);1998:  965–971.

 

 

 

 

Received on 30.04.2011       Modified on 14.05.2011

Accepted on 31.05.2011      © RJPT All right reserved