Pharmaceutical Aspects on the Formulations of Hydrogel: An Update
Ayushmaan Roy. Anjali Wahane, Siddharth Karankal, Prachi Sharma, Davesh Khutel, Onkarnath Singh, Vinay Shardul, Pitamber, Nausheen Sabha, Jyoti Dewangan, Ajay Dewangan, Akash Jangde, Chaya Rani, Tekeshwar Sahu, D. K. Tripathi, Mukta Agrawal, Ajazuddin, Gyanesh Sahu, Amit Alexander*
Rungta College of Pharmaceutical Sciences and Research, Kohka-Kurud Road, Bhilai, Chhattisgarh, India, 490024
*Corresponding Author E-mail: itsmeamitalex@gmail.com
ABSTRACT:
Hydrogels belongs to the classes of 3-dimensional cross-related polymer's communitywhich could withstand the wide varieties of environmental fluctuations. Thesebiomaterials can include massive quantum of biological fluids with extraordinaryswelling properties. whilst swelled, they exhibit opportune biocompatibility. Nowadaysdrug delivery enjoys several demanding situations where hydrogel might be onedeserving answer to those. Thanks to the specific properties of hydrogel for whichthey're employed except ionally in the field of biomedical sciences. For this reason,the raining techniques of hydrogel biomaterial and the evaluation of the differentclasses of above mentioned are most importance. literature's survey suggestedthat this 3-dimensional structure may be homo-polymeric, co-polymeric, andinterpenetrating polymer networks (IPN) based on guidance techniques. Polymericblends like semi-IPN have additionally been investigated to meet the precise requirements of biomedical science. Particularly emphasizing on biocompatibility,However, bendy strategies of synthesis and tailor in a posit ion physical residencehad made the hydrogels to be used as a drug transport tool in issue engineering.As scaffolds, they also offer structural integrity like tissues regeneration andrepair and as a drug carrier it must have enough mechanical strength to maintainthe structural integrity of drug moiety. In this review article a comprehensiveapproach has been made to describe the strategies of hydrogel synthesis withtheir inevitable properties.the present study is performed for the motivation of the graduates towards publication and research. Hence, we have encouraged the graduates to prepare an informative article on the present subject.
KEYWORDS: Hydrogel, Homo-polymer, Co-polymer, Interpenetrating network, Swelling, Mechanical, Biocompatible.
INTRODUCTION:
Recently hydrogels have received full-size attention. Hydrogels are 3-dimensional move-connected polymer network which can be clever sufficient to respond the fluctuations of environmental stimuli (pH, temp, ionic strength, electric subject, presence of enzyme and many others.) and swell or reduce as a result. inside the swollen state, they may be smooth and rubbery, akin to the residing tissue displaying first-rate biocompatibility [1]. consequently, those biomaterials are broadly utilized in exceptional subject of pharmaceutical and biomedical engineering [2].
With the advent of clinical technological know-how large numbers of recent healing moieties are located and demands specialized service for their transport into precise sites of the frame. it's far continually with the system scientists to delve similarly and to design more modern devices for the drug molecules which could serve even higher. This quest has ended up with the development of engineered biomaterials, hydrogel. hydrogels are capable of delivering genetically engineered prescribed drugs, viz. protein and peptides and enhance the healing efficacy and safety of medication administered via traditional methods. relying on the coaching methods this 3-dimensional structure of hydrogels could be homo-polymeric, co-polymeric, semi interpenetrating and interpenetrating polymer networks. these days, thermoplastic co-polymeric biodegradable hydrogels with premiere mechanical electricity were designed for biomedical packages along with drug transport gadget [3].
Over the years, blends were investigated to meet the precise need of biomedical field. such polymeric blends showed superior performances than the man or woman polymers and the range of application has been prolonged. carbohydrate based totally polymer blend is one among them and being investigated to broaden controlled release formulations [4]. semi-interpenetrating polymer networks (semi-IPN) is a way of blending two polymers in which only one is pass-connected inside the presence of another to supply a further non-covalent interplay among the two polymers [5]. semi-IPN have been evolved as a convenient approach for preparing multi-polymeric cloth and provided an opportunity choice to regulate the residences of herbal polymer-primarily based hydrogels [6]. They can serve as scaffolds which provide structural integrity to tissue constructs, manipulate drug and protein delivery to tissues and function adhesives or barriers among tissue and cloth surfaces. therefore, the properties of hydrogels are vital for tissue engineering and different areas of biomedical discipline. amongst these residences one should evaluate the swelling, mechanical and biocompatible houses before the hydrogel biomaterials are applied. writer has tried to describe briefly distinct methods of hydrogel education along with utility. the important houses that have to be evaluated, became also below the purview of this review article (Fig. 1).In the present study, graduates have gathered the information from the available resources and compiled the article so that it can be available to them in published form. Although the subject is explored one, the intention for the publication of the present work is to seed the interest towards the publication so that they can learn the process thoroughly.
CLASSIFICATION OF HYDROGEL:
Figure 1: Classification of hydrogels
PREPARATION METHODS OF HYDROGEL
Based totally at the methods of grounding, hydrogels can be categorized as (1) homo-polymer (2) copolymer (3) semi-interpenetrating community (4) interpenetrating community. homo-polymer hydrogels are go-connected networks of 1 type of hydrophilic monomer unit, while copolymer hydrogels are produced by means of pass-linking of co-monomer devices, as a minimum considered one of which must be hydrophilic to render them swellable. sooner or later, interpenetrating polymeric hydrogels are produced by making ready a first community this is then swollen in a monomer. the latter reacts to form a 2d intermeshing network shape.
1) Homo-polymeric Hydrogel
Homopolymers are cited polymer networks derived from unmarried species of monomer. it's far the primary structural unit and comprising of any polymer community [7]. Homopolymers can also have pass-connected skeletal structure depending on the nature of the monomer and polymerization method. cross-linked homopolymers are utilized in drug shipping gadget and in contact lenses. one possible way of making ready homo-polymeric hydrogel movie is the usage of poly (2-hydroxyethyl methacrylate) (polyHEMA) as a monomer, polyethylene glycol dimethacrylate as pass-linking agent and benzoin isobutyl ether because the UV-sensitive initiator. the movie turned into prepared in de-ionized water and dealt with UV radiation (λ = 253.7 nm, eleven mm distance from the source for 20 minutes). the film become then immersed for 24 h in water till it is completely saturated in order to remove toxic or unreacted substances that would harm a living tissue. except touch lenses, PHEMA also can be carried out in synthetic skin manufacturing and burn dressings, as it guarantees right wound-recuperation situations. it's also used for bone marrow and spinal cord cell regeneration, scaffolds for selling mobile adhesion and in synthetic cartilage manufacturing [8-10]. another low molecular weight move-linking agent used inside the synthesis of polyHEMA hydrogel is 1,1,1-trimethylol propane trimethacrylate. the hydrogel obtained with this agent is tender and includes 30-forty % of water and prominent with the aid of its excessive oxygen permeability. those residences have translated its use in contact lenses, as matrices for drug delivery machine and smooth tissue implants. if the mechanical properties of the hydrogel are progressed its utility should similarly be prolonged. cretu et al. has progressed the hydrogel through synthesizing the amphiphilic fabric or introducing hydrophobic compounds (caprolactone) into its structure [11].
2) Co-polymeric hydrogel
Co-polymeric hydrogels are composed of varieties of monomer in which at least one is hydrophilic in nature. gong et al. [12] synthesized the biodegradable triblock poly (ethylene glycol)-poly (ε- caprolactone)- poly (ethylene glycol) (percent) co-polymeric hydrogel for the improvement of drug delivery gadget. the mechanism contain right here is the ring-starting copolymerization of ε-caprolactone. in the triblock synthesis mpeg changed into used as initiator, stannous octoate as catalyst and hexamethylenediisocyanate as coupling agent. this co-polymeric block is capable to form hydrogel whilst it is carried out in-situ. the observe well-known shows that the hydrogel was biodegradable and bio-like minded. it became able to liberating each the hydrophobic and hydrophilic capsules along with proteins over a sustained time period. this thermosensitive hydrogel has additionally been evaluated for cellular encapsulation and tissue restore programs. in every other take a look at, kim and his co-people attempted peg based totally hydrogels to evaluate its feasibility to be used as a drug shipping gadget [13]. They organized copolymers of methacrylic acid (MAA) with PEG-PEGMA by using free-radical photopolymerization the use of tetra (ethylene glycol) dimethacrylate as move-linker. the pass-linking befell inside the presence of an initiator, 1-hydroxycyclohexyl phenyl ketone in nitrogen surroundings for 30-minutes under UV light. The hydrogel turned into successfully loaded with insulin. the authors claim that the swelling behavior and therefore the price of launch strongly rely upon the molecular weight of PEG. Cascone et al. [14] describe the synthesis of PVA based hydrogel as scaffolds for tissue engineering. a 10% aqueous solution of PVA become uncovered to a high temperature in an autoclave (120°c/1h) after which mixed with a appropriate modifier such as gelatin, dextrin, hyaluronic acid, collagen, dextrane or chitosan. the aggregate changed into then subjected to eight cycles of freezing (253 ok/1 h) and thawing (rt/30 min). this freeze-thawing cycle results in the formation of PVA crystals which act as crosslinks among the polymer chains. the hydrogel become additionally evaluated as a matrix for drug shipping gadget. Lugao et al. [15] received PVP hydrogels the usage of unique irradiation doses (5-15 KGy) and exceptional components: peg (mw 600, 6000), polyetheleneoxide (PEO) (400000) and glycerol. within the look at, glycerol and PEO had been used to lessen the go-linking density of the PVP community, whereas peg increases the pliability of the gels as a result of the plasticizing effect. moreover, PVP/PEG hydrogels are sterile and non-cytotoxic, which makes PEG a really perfect addition to biomedical hydrogels designed as a dressing material. Wang et al. [16] cautioned the use of cellulose or carboxymethyl cellulose (CMC) in the synthesis of PVP primarily based hydrogel. CMC is water soluble and bio-compatible. its low cost and high abundance had been also the reasons for its mixing with PVP. the PVP/CMC blend yields a hydrogel with desirable mechanical property (mechanical energy higher than pure CMC and flexibility superior to that of natural PVP hydrogels). its high-water uptake potential, improved biodegradability and non-noxious pleasant translated it as perfect hydrogel dressing material. Thomas et al. [17] synthesized a co-polymeric hydrogel by way of free radical copolymerization of monomers particularly acrylamide and acrylic acid the use of N, N-methylenebisacrylamide and potassium persulfate because the move-linker and initiator respectively. The reactions had been carried out in aqueous medium. the synthesized hydrogel became transparent in nature.
3) Semi- Inter Penetrating Network (Semi-IPN)
If one polymer is linear and penetrates another pass-connected community without any other chemical bonds between them, it is known as a semi-inter penetrating network [18]. semi-IPN can more successfully hold speedy kinetic reaction quotes to pH or temperature because of the absence of limiting interpenetrating elastic community, at the same time as nonetheless imparting the blessings like modified pore length and gradual drug release and many others. one instance to justify the state of affairs is the entrapment of linear cationic polyallyl ammonium chloride in acrylamide/ acrylic acid copolymer hydrogel which imparted each higher mechanical power and absolutely reversible pH switching of theophylline release. This pH sensitive semi-IPN become synthesized with the aid of template copolymerization inside the presence of N, N′-methylene bisacrylamide as a pass-linking agent [19].
4) Inter Penetrating Network (IPN)
IPN are conventionally described as intimate aggregate of 2 polymers, at the least one of that is synthesized or cross-linked within the on the spot presence of the opposite [20]. This is normally achieved by means of immersing a pre-polymerized hydrogel into an answer of monomers and a polymerization initiator. IPN approach can conquer thermodynamic incompatibility takes place due to the permanen interlocking of network segments and confined segment separation can be received. the interlocked shape of the move-linked IPN additives are believed to make sure balance of the bulk and surface morphology [21,22]. the principle advantages of IPN are fantastically dense hydrogel matrices can be produced which characteristic stiffer and harder mechanical residences, controllable physical residences and greener drug loading in comparison to traditional hydrogels. drug loading is often completed alongside the polymerization of the interpenetrating hydrogel segment [23]. IPN pore sizes and floor chemistries also can be controlled to music the drug release kinetics, interplay among the hydrogel and the surrounding tissues at the side of its mechanical homes [24].
PROPERTIES OF HYDROGEL
Hydrophilic gels referred to as hydrogels receive full-size interest for their use within the field of pharmaceutical and biomedical engineering. this fabric may be used as a carrier for drug and different therapeutic bio-molecule simplest if it's far biodegradable, biocompatible and non-toxic in situ. thus, once the biomaterials are prepared one should evaluate the function residences like swelling conduct, mechanical properties and toxicity studies and so on so that the hydrogel can be used correctly within the worried biomedical area.
1) Swelling houses
All polymer chains in hydrogels are go connected to every other either bodily or chemically and hence, taken into consideration as one molecule no matter its size. for that reason, there may be no concept of molecular weight of hydrogels and consequently, every so often called infinitely huge molecules or splendid macromolecules. a small change in environmental situation might also trigger fast and reversible changes in hydrogel. the alteration in environmental parameters like pH, temperature, electric powered signal, presence of enzyme or other ionic species might also result in a alternate in physical texture of the hydrogel. those adjustments may also arise at macroscopic degree as precipitate formation, adjustments in length and water content material of hydrogels. The distinction in concentration of mobile ions within the hydrogel indoors relative to external solution (osmotic stress), adjustments in solvent pH, drives the extent exchange. hydrogels with acidic or simple purposeful corporations reply to the fluctuations in the outside environmental pH. diploma of ionization of the functional groups dictates its swelling profile and subsequently the extent trade. polyacrylic acid is such type of pH sensitive hydrogel in which swelling ratio modifications because of the ionization of carboxyl companies at the polymer chain. in other experiment, temperature-brought on section transitions and microenvironment of PNIPAM based totally hydrogels had been studied in water the use of nine-(4-N,N-dimethylaminopHenyl) phenanthrene (DP) as an intramolecular fluorescence probe.
2) Mechanical houses
Mechanical properties of hydrogels are very crucial from the pharmaceutical and biomedical factor of view. the assessment of mechanical property is crucial in diverse biomedical programs viz. ligament and tendon restore, wound dressing material, matrix for drug delivery, tissue engineering and as cartilage substitute cloth. the mechanical homes of hydrogels should be such that it may preserve its physical texture at some stage in the shipping of healing moieties for the predetermined period of time. Converting the degree of crosslinking the preferred mechanical assets of the hydrogel can be accomplished. growing the diploma of crosslinking a stronger hydrogel can be performed even though the higher diploma of crosslinking decreases the % elongation of the hydrogels creates a greater brittle shape.
3) Biocompatible Properties
It's miles critical for the hydrogels to be biocompatible and risk-free in order to make it applicable in biomedical discipline. most polymers used for this cause must pass cytotoxicity and in-vivo toxicity checks. biocompatibility is the capability of a fabric to perform with an appropriate host reaction in a specific application. Biocompatibility is composed essentially of factors: (a) bio-protection i.e. appropriate host response not simplest systemic however also nearby (the surrounding tissue), the absence of cytotoxicity, mutagenesis, and/or carcinogenesis and (b) bio-functionality i.e. the ability of cloth to carry out the precise venture for which it's far meant. this definition is particularly relevant in tissue engineering because the nature of tissue construct is to continuously interact with the frame through the restoration and cell regeneration manner in addition to in the course of scaffold degradation.
3.1) Evaluation of biocompatibility
In vitro cell culture assessments are frequently used to display screen the tissue compatibility of implantable devices. the cellular way of life techniques is additionally called cytotoxicity checks. 3 primary mobile subculture assays are used to evaluate biocompatibility of the hydrogels encompass: a) elution (extract dilution) b) direct contact c) agar diffusion. These assays are defined in the us pharmacopeia and in standards published by using the worldwide standards employer. these are morphological assays and the final results is measured via observation of adjustments in cell morphology. the in vivo evaluation of tissue compatibility of a hydrogel is the knowledge of chemical composition of the biomaterial and the conditions of tissue exposure (such as nature, diploma, frequency and period of exposure). ideas commonly implemented to the organic evaluation of hydrogels are defined as follows: the material(s) of manufacture; supposed components, procedure contaminants, and residues; leachable materials; degradation products; other additives and their interactions within the very last product; the homes and traits of the very last product. maximum of the issues associated with hydrogel concerning toxicity, are the unreacted monomers, oligomers and initiators that leach out at some stage in software. so, it is crucial to assess the toxicity of the hydrogel components like monomers, initiators and different building blocks used for its synthesis. editing the kinetics of polymerization and substantial washing of the resulting hydrogel can lessen the toxicity. the formation of hydrogels without any initiators and using exchange direction like radiation can also get rid of the hassle of the residual initiator.
EVALUATION STUDY
Physical Appearance:-
• Physical appearance i.e. color, odorwere tested by visual inspection of prepared gels. Though marketed formulation were considered as a reference.
SpreadabilityTest:-
• Spreadability of gel can be observed or determine by the application of gel over the skin or to the smooth surface from which we identify the nature of hydrogel.
• Gel should be spread readily on the affected area and it should be free from gritty particles.
pH determination:-
• pH of the formulated gel were tested and can be determine by using pH meter. 1% of hydrogel formulation in deionized water were prepared and pH can be determined.
Drug Content:-
• From the prepared gel, 1gm of each gel is mixed with the suitable solvent.
• Through membrane filter, the resultant mixture were filtered and absorbance were noted, from the equation drug content can be calculated which is obtained by linear regression analysis of calibration curve.
Determination OF Viscosity:-
• By using Brookfield viscometer at 100 rpm at temperature of 25 degree C, viscosity of gel formulation can be determined.
Stability Test:-
• At different storage condition stability test were performed ie; 2 to 4 degree C (cool room), 25 degree C (room temperature), and 40 degree C (oven).
•
Stability testing of packed formulation from aluminium tube can be done for 3 month as per ICH norms at a temperature.
•
Sample placed at various storage condition and samples were withdrawn at a regular time interval of 1 month for over a period of 3 month and observed weather any changes takes or not in pH, spreadability, drug content.
If any changes take place in evaluation parameter of gel then tests were carried out in triplicate and value of the observed values was notes
CONCLUSION:
The precise requirements of superior drug shipping ought to without difficulty be met by using hydrogels. big range of techniques for the synthesis of these novel biomaterials has extended its utility from drug transport system to tissue engineering scaffolds, wound dressing fabric, bio separators, gene shipping device and biosensors and so on. Further investigate into the fundamentals of multi-polymer primarily based hydrogel and their homes, may deliver raise a singular method for imposing the biomaterials inside the biomedical field in a higher way.In all, it was good to see that the students were propelled towards the said target and they have now known the basics of the publication process. Henceforth, this article will prove to be a milestone in their future research carrier.
AKNOWLEDGMENT:
The author wants to show a sincere gratitude to the Rungta College of Pharmaceutical Sciences and Research for providing necessary facilities for the completion of work.
CONFLICT OF INTEREST:
None
REFERENCES:
1. Prashant PK, Vivek BR, Deepashree ND, Pranav PP. Hydrogels as a drug delivery system and applications: a review. Int JPharm Pharm Sci. 2012; 4: 1-7.
2. Das N, Bera T, Mukherjee A. Biomaterial hydrogels for different biomedical applications. Int J Pharm Bio Sci. 2012; 3: 586-595.
3. Oh SB, Choi YK, Cho CS. Thermoplastic hydrogel based on pentablock copolymer consisting of poly(γ-benzyl L-glutamate) and poloxamer. J Appl Polym Sci. 2003; 88: 2649-2656.
4. Isiklan N. Controlled release of insecticide carbaryl from sodium alginate, sodium alginate/gelatin, and sodium alginate/sodium carboxymethyl cellulose blend beads crosslinked with glutaraldehyde. J Appl Polym Sci. 2006; 99: 1310-1319.
5. Zhang JT, Bhat R, Jandt KD. Temperature-sensitive PVA/PNIPAAm semi-IPN hydrogels with enhanced responsive properties. Acta Biomater. 2009; 5: 488-497.
6. Krishna Rao KSV, Vijaya Kumar NB, Subha MCS, Sairam M, Aminabhavi TM. Novel chitosan-based pH-sensitive interpenetrating network microgels for the controlled release of cefadroxil. Carbohydr Polym. 2006; 66: 333-344.
7. Iizawa T, Taketa H, Maruta M, Ishido T, Gotoh T, Sakohara S. Synthesis of porous poly (N-isopropylacrylamide) gel beads by sedimentation polymerization and their morphology. J Appl Polym Sci. 2007; 104: 842-850.
8. Sykova E, Jendelova P, Urdzikova L, Lesny P, Hejcl A. Bone marrow stem cells and polymer hydrogels-two strategies for spinal cord injury repair. Cell Mol Neu robiol. 2006; 26: 1111- 1127.
9. Kubinova S, Horak D, Kozubenko N, Vanecek V, Proks V, Price Jet al. The use of superporous Ac-CGGASIKVAVS-OH-modified PHEMA scaffolds to promote cell adhesion and the differentiation of human fetal neural precursors. Biomaterials 2010; 31: 5966-5975.
10. Bavaresco VP, Zavaglia CAC, Reis MC, Gomes JR. Study on the tribological properties of pHEMA hydrogels for use in artificial articular cartilage. Wear 2008; 265: 269-277.
11. Cretu A, Gattin R, Brachais L, Barbier-Baudry D. Synthesis and degradation of poly (2-hydroxyethyl methacrylate)-graft-poly (ε-caprolactone) copolymers. Polym Degrad Stab. 2004; 83:399-403.
12. Gong CY, Shi S, Dong PW, Kan B, Gou ML, Wang XH et al. Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel. Int J Pharm. 2009; 365: 89-99.
13. Lin CC, Anseth KS. PEG hydrogels for the controlled release of biomolecules in regenerative medicine. Pharm Res. 2009; 26:631-643.
14. Kim B, Peppas NA. Poly(ethylene glycol)-containing hydrogels for oral protein delivery applications. Biomed Microdevices 2003; 5: 333-341.
15. Benamer S, Mahlous M, Boukrif A, Mansouri B, Youcef SL.Synthesis and characterisation of hydrogels based on poly(vinyl pyrrolidone). Nucl Instrum Methods Phys Res. 2006;248: 284-290.
16. Christensen L, Breiting V, Vuust J, Hogdall E. Adverse reactions following injection with a permanent facial filler polyacrylamide hydrogel (aquamid): causes and treatment. Eur J Plast Surg. 2006; 28: 464-471.
17. Cascone MG, Lazzeri L, Sparvoli E, Scatena M, Serino LP, Danti S. Morphological evaluation of bioartificial hydrogels as potential tissue engineering scaffolds. J Mater Sci Mater Med.2004; 15: 1309-1313.
18. Lugao AB, Rogero SO, Malmonge SM. Rheological behaviour of irradiated wound dressing poly(vinyl pyrrolidone) hydrogels. Radiat Phys Chem. 2002; 63: 543-546.
19. Wang M, Xu L, Hu H, Zhai M, Peng J, Nho Y et al. Radiation synthesis of PVP/CMC hydrogels as wound dressing. Nucl Instrum Methods Phys Res. 2007; 265: 385-389.
20. Thomas V, Yallapu MM, Sreedhar B, Bajpai SK. A versatile strategy to fabricate hydrogel-silver nanocomposites and investigation of their antimicrobial activity. J Colloid Interface Sci. 2007; 315: 389-395.
21. Zhang YX, Wu FP, Li MZ, Wang EJ. pH switching on-off semi-IPN hydrogel based on cross-linked poly(acrylamide-co-acrylic acid) and linear polyallyamine. Polymer 2005; 46: 7695-7700.
22. Murthy PSK, Murali Mohan Y, Varaprasad K, Sreedhar B, Mohana Raju K. First successful design of semi-IPN hydrogelsilver nanocomposites: a facile approach for antibacterial application. J Colloid Interface Sci. 2008; 318: 217-224.23.
23. Gils PS, Ray D, Sahoo PK. Designing of silver nanoparticles in gum arabic based semi-IPN hydrogel. Int J Biol Macromol. 2010; 46: 237-244.
24. Ju HK, Kim SY, Kim SJ, Lee YM. pH/temperature-responsive semi-IPN hydrogels composed of alginate and poly(Nisopropylacrylamide). J Appl Polym Sci. 2002; 83: 1128-1139
Received on 08.04.2018 Modified on 11.05.2018
Accepted on 26.05.2018 ©A&V Publications All right reserved
Res. J. Pharma. Dosage Forms and Tech.2018; 10(2): 79-84.
DOI: 10.5958/0975-4377.2018.00012.5