A Review on Biocompatible Hydrogel: Formulation Aspect and Evaluation
Shubham Tripathi, Somnath Patel, Ritesh Patel, Shraddha,Pushpendra, Sachin,Neetish, Mahendra, Kuldeep, Prashant, Rajesh Patel, Girish, Nitin, Tomanlal, Amrita Thakur, Mukta Agrawal, Ajazuddin,
D. K. Tripathi, Amit Alexander*
Rungta College of Pharmaceutical Sciences and Research, Kohka-Kurud Road, Bhilai, Chhattisgarh, India, 490024
*Corresponding Author E-mail: itsmeamitalex@gmail.com
ABSTRACT:
Many predefined ways are now a day adopted to interface with biological tissues. One such significant class of biomaterials are hydrogels, which are defined as highly hydrated materials. Hydrogels are designed to absorb a large amount of water or biological fluids due to its three-dimensional, hydrophilic, polymeric network. They closely simulate natural living tissue, more so than any other class of synthetic biomaterials because of their high- water content, porosity,and soft consistency.They are chemically stable but may degrade and gradually disintegrate up to dissolve. Now a day they become more popular because of their unique property of flexibility and biocompatibility. Hydrogels can be produced by both natural and synthetic polymers. These polymers undergo physical and chemical cross-linking to produce hydrogels. Due to their resemblance to the living tissue, they have the immense possibility to use hydrogels in the biomedical field. Some of the well-known use of hydrogels include manufacturing contact lenses, hygiene products, tissue engineering scaffolds, drug delivery system and wound dressings. The current review article deals with information about the hydrogels, their various types, preparation methods along with an evaluation of the same.Also, 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, polymeric network, porosity, biocompatibility, biomedical.
INTRODUCTION:
The easiness in manufacturing the hydrogel has gained greatlyin interest in recent times. Hydrogels are three-dimensional, hydrophilic,logic, polymeric networks capable of absorbing large amounts of water or biological fluids. They swell in water,but they do not get dissolved in it. The three-dimensional structure of hydrogel is formed by polymer chain cross-linking. This cross-linking can be achieved by covalent bonds, hydrogen bonding, Vander Waals forces,etc. [1]
Hydrogels are matrixes made up of polymers which swells but do not get dissolved in water. Hydrogels are also referred as smart hydrogels as they have structural and chemical responsive moieties which exhibit responsiveness to external stimuli including temperature, pH, ionic concentration, light, magnetic fields, electrical fields and chemicals [2,3]. The interaction of water and polymers decides the properties of a hydrogel. The water prevents thepolymer aggregation which ultimately forms a compact mass while thepolymer prevents water from flowing out of gel matrix. [4]Hydrogels are highly permeable structure. Its permeability depends mainly on the density of cross-linking assembly present in the gel matrix as well as their affinity towards the aqueous atmosphere in which they gradually swell up.The permeability of hydrogel helps not only in the loading of drug in gel matrix but also regulates the release of the drug through the matrix. However, the release of drug from such gel matrix occurs mainly via depot formation which causes the drug release slowly by maintaining a high concentration of drugs in local tissues. 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.
CLASSIFICATIONOF HYDROGELS
There are various ways to classify hydrogels. Some of them include classificationon the basis of the bond arrangement, on the basis of preparations, classification on the basis of source, polymeric compositions and many more. These are also classifiedon the basis of their biodegradable properties as well as application [5].
· Classification on the basis ofthe bond arrangement
a. Physical Hydrogel: These are the type of hydrogels which are connected internally by hydrogen bonding or hydrophobic interaction.
e.g.: - polyethylene glycol (PEG), Poly (propylene oxide) (PPO), Poly (butylene oxide) (PBO), etc.
b. Chemical Hydrogel: These are the types of hydrogels that are permanently linked by covalent bond grips forming the gel network.
e.g.: -polyvinyl alcohol, etc.
· Classification on the basis of source
On the basis ofsource, hydrogels can be classified as natural or synthetic origin[6].
a. Natural: starch, cellulose, chitosan, etc.
b. Synthetic:Poly(acrylic-co-vinylsulfonic) acid, Polyvinyl alcohol, etc.
· Classification by polymeric composition[7]
a. Homopolymeric hydrogels:These hydrogels consist of polymer network prepared by single species of a monomer. Their structure mainly depends on the nature of the monomer as well as the technique of polymerization.
e.g.: -poly (2-hydroxyethyl methacrylate) (polyHEMA), polyethylene glycol dimethacrylate, etc.
b. Copolymeric hydrogels: These types of hydrogel comprise two or more different monomer species. The monomer species consists of at least one hydrophilic component which can be arranged in random, block or alternating configuration with the polymer network.
e.g.: -poly (ethylene glycol)-poly (ε- caprolactone)- poly (ethylene glycol) (PECE) co-polymeric hydrogel, etc.
c. Multipolymer interpenetrating polymeric hydrogels (IPN): These are an important class ofhydrogels. They are made up of two independent cross-linked synthetic or natural polymercomponents, contained in a network form. In some cases, one component is a crosslinked polymer,andanothercomponent is not- cross-linked polymer, which is called as a semi-IPN hydrogel.
e.g.,A semi-IPN hydrogel of guar gum (GG) and poly (methacrylic acid), etc.
· Classification bythe configuration
Configuration is defined as, an arrangement of parts or elements in a particular form, figure, or combination. Hence, this type of classification of hydrogel mainly includes the structure of the polymer used to prepare a hydrogel.
a. Amorphous (non- crystalline)
b. Crystalline
c. Semi-Crystalline: A complex mixture of amorphous and crystalline phases.
· Classification by cross-linking
They are classified by their cross-linking junctions.
a. Physical Cross-linking: These type of linking have transient junctions that arise from either polymer chain entanglements or interactions such as ionic interactions, hydrogen bonds, etc.
b. Chemical Crosslinking: These type of linking contains permanent junction in polymer chains.
CHARACTERISATION OFHYDROGELS [8]
Hydrogels receive significant attention for their use in the field of pharmaceutical and biomedical engineering because of the following properties.
1. Swelling properties
Hydrogel gets easily affected by the environmental condition. These effects are reversible as well as fast. The change in an environmentalcondition like electric signal, pH, temperature,and presence of enzymes or other species lead to change in the physical form of the hydrogel. This property of hydrogel helps in the release of the drug gradually like a depot form.
2. Mechanical properties
The mechanical property of the hydrogel defines the stability of the polymers linked together by different forces. The mechanical property of hydrogel can be achieved by changing the degree of crosslinking. By increasing the degree of crosslinking, a stronger hydrogel will be formed,but it will lead to the formation of a more brittle structure.
3. Biocompatible properties
Biocompatibility and nontoxicity are the essential elements of the hydrogel. The polymers which are used for the preparation of hydrogels must pass cytotoxicity and in vivo toxicity tests. Biocompatibility studies are performed to identify the biosafety and bio-functionality of the host response for a particular application.
EVALUATION OF HYDROGEL[9]
The evaluation of hydrogels depends on the type of hydrogel prepared. Following are the generalized evaluation criteria for hydrogels.
A) Morphological characterization:Hydrogels are characterized for morphology which is analyzed by equipment like stereomicroscope. Also, the texture of these biomaterials is analyzed by SEM (Scanning Electron Microscope) to ensure that hydrogels retain their granular structures.
B) Fourier Transform Infrared Spectroscopy(FTIR) analysis:FTIR spectra of the hydrogel are recorded using FTIR spectrophotometer to determine their structure and intermolecular interactions. Thoroughly ground IPN samples are mixed with dried KBr and discs are being prepared by compression under vacuum. Spectra are recorded with a resolution of 1 cm-1.
C) Swelling behavior:Hydrogels are prepared by polymers. These polymers have property to get swell in particular pH. The hydrogels are evaluated for their swelling property as they have nature to imbibe water or biological fluid in it. The process involves keeping of hydrogel to a particular pH and removing the same time to time till constant weight is achieved.
Swelling ratio% = Ws-Wd/Wd * 100,
where Ws- Weight of swollen hydrogels Wd- the weight of dry hydrogels
D) Drug content:Hydrogels, generally entrap the drug molecule. The amount of crosslinking affects the drug content. The drug content can be evaluated by taking approximately 1 g of the prepared hydrogel in 100 ml of a suitable solvent of the desired pH. Then, at particular time intervals aliquots are prepared by suitable dilution. The absorbance of these are then measured,andfinally, the drug content is identified by linear regression analysis of calibration curve.
E) In vitro studies:The in vitrostudies include release study of the drug in a particular medium. As we know release from hydrogel follows depot pattern of release. The process includes keeping hydrogels in a dissolution medium of the desired pH and withdrawing the sample from it at specific time intervals. The absorbance calculation will give the amount of drug release through the hydrogel.
APPLICATION OF HYDROGELS IN DRUG DELIVERY
1) Ocular implants and contact lenses:
The most widely used application of hydrogels is soft contact lenses. The hydrogel perfectly adapts to the ocular curvature which makes it comfortable material to use in the ocular region. Additionally, they permit atmospheric oxygen to reach the cornea by dissolving water of lens. Ophthalmic drug delivery is gaining significant interest now a day because of medicated contact lens because theysignificantly increase the residence time of the drug in the precorneal area. They provide the geometricbarrier provided by the contact lenses to the drug when it diffuses out from the gel matrix intothe tear film [10].
2) Tissue regeneration and tissue engineering:
Hydrogels are used in tissue engineering and regeneration. They have a matrix-like structure which has been utilized to support and contribute tothe repair of a range of tissues such as bones, cartilage, nerves, vessels,and skin [10]. A three-dimensional artificial template called as scaffolds act on tissue targeted for reconstruction. The high porosity of hydrogel allows for the diffusion of cells during migration and additionally the transfer of nutrients and waste products.The micronized hydrogels (microgels) have been used to deliver macromolecules likephagosomes into the cytoplasm of antigen-presenting cells. The release is because of acidic conditions. Such hydrogels moldthemselves to the pattern of membranes of the tissues and havesufficient mechanical strength. This property of hydrogels is also used in cartilage repairing [11].
3) Biosensors
Hydrogels are usedas supporting tool for immobilization of enzymes by preparation of biosensors.Biosensors may not only attract or repels the substrate or product to its surface, but it also acts as a barrier for free diffusion of molecules. Thus, these help in concentrating or depleting the immediate vicinity of the enzyme.
4) Wound Dressings
The amorphous hydrogel has the property that can take up the shape of wounds. Thus, hydrogels are also used in wound dressings. The amorphous or shapeless hydrogels are composed of insoluble non-crosslinked hydrophilic polymers such as polyvinylpyrrolidine or polyacrylamide in the form of a gel containing 70-95% water. They can be packedin tubes, spray bottles or foil packs. The gel is applied directly to thewound and is usually covered with a secondary dressing. Exudate isabsorbed into the gel while moisture evaporates through the secondary dressing [12].
5) Oral
The highest affined route that has aroused interest among researchesregarding hydrogel delivery is oral route. But, this delivery of the drugin the form of hydrogel involves mainly two strategies. One is to develop mucoadhesive hydrogels that interact with mucous resulting in physical entanglement and second is through Van der Waals forces due to the presenceof hydroxyl, carboxyl, amine, and amide groupson the surface of the polymeric matrix, which prolongs the residence time of the dosage form on theabsorption site. The first pass metabolism and prevention of degradation of the drug in GI tract can be achieved by using devices which can be placed in the buccal cavity. The other area is colon to be considered for hydrogel drug delivery other than GI tract.Various hydrogels, particularly enzyme-sensitive hydrogels, are currently beingconsidered and developed for use in colon-specific drug delivery [13].
CONCLUSION:
Hydrogels are defined as hydrophilic polymeric three dimensional structure which are capable of absorbing large amounts of water or biological fluids.Because of this they are widely being used in the medical industry as dressings and even in tissue regeneration and tissue engineering, etc.Enormous developments have been made in the properties of hydrogels used in drug delivery.However further advancementneeds to be made to improve the applicability of hydrogels for efficient drug delivery. However, more progress needs to be attained in the delivery of hydrophobic molecules. Development in such parts would significantly improve the delivery of drugs through hydrogels totargeted region in the body. 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.
REFERENCE:
1. Caló E, Khutoryanskiy VV.Biomedical Applications Of Hydrogels: A Review Of Patents And Commercial Products, European Polymer Journal.2015;65:252-267.
2. Das N. Preparation Methods And Properties Of Hydrogels: A Review. International Journal of Pharmacy and Pharmaceutical Sciences.2013;5(3):112-117.
3. Hoare TR, Kohane DS. Hydrogels In Drug Delivery: Progress And Challenges. Polymer.2008;49(8):1993-2007.
4. Phadke A, Zhang C, Arman B, ChengChih Hsu, Mashelkar R. Lele A, Tauber M, Arya G,andVarghese S.Rapid Self-Healing Hydrogels.Proceedings of the National Academy of Sciences.2012;109:4383-4388.
5. Dwivedi S, Khatri P, Mehra GR,Kumar V. Hydrogel - A Conceptual Overview. International Journal of Pharmaceutical and Biological Archives.2011; 2(6):1588-1597.
6. Ahmed EM. Hydrogel: Preparation, Characterization And Applications. Journal of advanced research.2015;6(2):105-121.
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. Journal of applied polymer. 2007; 104: 842-850.
8. Singh SK, Dhyani A,Juyal D. Hydrogel: Preparation, Characterization And Applications. The Pharma Innovation Journal .2017; 6(6): 25-32.
9. Himi M, Maurya SD, Preparation And Evaluation Of Stomach Specific IPN Hydrogels For Oral Drug Delivery: A Review. Journal of Drug Delivery and Therapeutics; 2013, 3(2), 131-140.
10. Swarbrick J, Encyclopedia Of Pharmaceutics, 4thedition,Vol III, F-O, 6000 Broken Sound Parkway NW, Suite300, Boca Raton, FL 33487-2742, Taylor and Francis Group,, 2013.
11. Bindu M, Ashok. V, Chatterjee A. Review Article As A Review On Hydrogels As Drug Delivery In The Pharmaceutical Field. International Journal of pharm and chemical sciences ISSN: 2277:5005:642-661.
12. Aulton M., Aulton’s pharmaceutics, The Design and Manufacture of Medicines, Third Edition, Elsevier’s Health Sciences Rights Department, 1600 John F. Kennedy Boulevard, Suite 1800, Philadelphia, PA 19103-2899, Harcourt Publishers Limited 2001.
13. Chien Y. Novel drug delivery systems. second edition, New York, 52 Vanderbuilt Avenue, Informa Healthcare USA, Inc,2009.
Received on 11.04.2018 Modified on 25.05.2018
Accepted on 13.06.2018 ©A&V Publications All right reserved
Res. J. Pharma. Dosage Forms and Tech.2018; 10(2): 119-122.
DOI: 10.5958/0975-4377.2018.00019.8