Hydrogel in Drug Delivery

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Hydrogels in Drug Delivery :

Hydrogels in Drug Delivery

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C O N T E N T S Introduction Classification of Hydrogels Advantages of Hydrogels Disadvantages of Hydrogels Types of Hydrogels Monomers Used In The Synthesis of Synthetic Hydrogels Method of Preparation of Hydrogels Characterization of Hydrogels Common Uses For Hydrogels Pharmaceutical Applications of Hydrogels Summary and conclusions References Acknowledgement 2

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Introduction: Definition: 3 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.

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Introduction: 4 Hydrogels are crosslinked polymer networks that absorb substantial amounts of aqueous solutions. These crosslinks provide the network structure and physical integrity. Hydrogels can contain over 99.9% water. The high water content of the materials contributes to their biocompatibility.

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Classification Of Hydrogels: 5

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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 result of such a change. 6

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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. 7

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Disadvantages of Hydrogels: Hydrogels are expensive. Hydrogels causes sensation felt by movement of the maggots. Hydrogels causes thrombosis. The surgical risk associated with the device implantation and retrieval. Hydrogels are non-adherent ; they may need to be secured by a secondary dressing. 8

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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 9

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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. 10

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Types of Hydrogels : Synthetic Polymers e.g.:Poly (vinyl alcohol) Disadvantages: Low biodegradability Can include toxic substances 11

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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. Classification Of Hydrogel Based Systems: 12

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Monomer abbreviation Monomer HEMA Hydroxyethyl methacrylate HEEMA Hydroxyethoxyethyl methacrylate HDEEMA Hydroxydiethoxyethyl methacrylate MEMA Methoxyethyl methacrylate MEEMA Methoxyethoxyethyl methacrylate Monomers Used In The Synthesis Of Synthetic Hydrogels: 13

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Monomer abbreviation Monomer EG Ethylene glycol EGDMA Ethylene glycol dimethacrylate NVP N-vinyl-2-pyrrolidone AA Acrylic acid PEGMA PEG methacrylate Monomers Used In The Synthesis Of Synthetic Hydrogels: 14

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Method Of Preparation Of Hydrogels: Crosslinking Isostatic Ultra High Pressure Nucleophilic Substitution Reaction Using Gelling Agents Use Of Irradiation Freeze Thawing 15

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Crosslinking: Linear polymers Crosslinking Chemical compounds Irradiation Monomers used in the preparation of the ionic polymer network contain an ionizable group, gets ionized, or undergoes substitution after the polymerization is completed. 16

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Isostatic Ultra High Pressure : Suspension of natural biopolymers (starch) ultrahigh pressure of 300-700 MPa 5or 20 min 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. 17

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Nucleophilic Substitution Reaction: Methacyloyl chloride 2-dimethylamino ethylamine. Nucleophilic substitution. N-2-dimethyl amino ethyl- methacryalmide (DMAEMA) (a pH and temperature sensitive.) 18

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By Using Gelling Agents: Examples Glycophosphate . 1-2 Propanediol . Glycerol. Mannitol . Drawbacks Turbidity. Presence of negative charged moieties pose problem of interaction with the drug. 19

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Use Of Irradiation: Irradiation method processing is costly Mechanical strength of such Hydrogels is less. Advantages Drawbacks Irradiation method is convenient. Hydrogels prepared by microwave irradiation are more porous than conventional methods. 20

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Freeze Thawing: Opaque in appearance Little swelling capacity. Advantage Drawbacks Sufficient mechanical strength. Good Stability. 21

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Characterization Of Hydrogels: 22

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Atomic Force Microscope Atomic Force Microscopy (AFM): A Multimode Atomic Force Microscope form Digital Instrument is used to study the surface morphology of the hydrogels . 23

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X-ray Diffraction: Used to understand whether the polymers retain their crystalline structure or they get deformed during the pressurization process 24

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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 25

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Rheology : Hydrogels are evaluated for viscosity under constant temperature (4°C) by using Cone Plate viscometer. Cone plate viscometer 26

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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. 27

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Swelling degrees (SDs) of hydrogels were measured at 37 0 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. Swelling Behavior: 28

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Swelling Behavior: The SD was calculated as follows: W0 = Weight of the original Hydrogel Wt = is the weight of hydrogel at various swelling times SD (%)= (Wt/ Wo )×100 Picture of a swollen Hydrogel 29

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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 30

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In-vitro Release Study For Drugs: Dissolution media: Buffer solution with various pH values. R.P.M: 90 rpm. Temperature : 37 0 C. Sink condition is maintained by replacing the buffer periodically. Dissolution apparatus 31

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Common Uses For Hydrogels: 32

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Pharmaceutical Applications Of Hydrogels: Peroral Drug Delivery Drug Delivery In The Oral Cavity Drug Delivery in the G.I.T Ocular Delivery Transdermal Delivery Subcutaneous Drug Delivery Hydrogels To Fix Bone Replacements Tissue Engineering Protein Drug Delivery Topical Drug Delivery 33

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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. Peroral Drug Delivery: 34

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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. Peroral Drug Delivery: 35

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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. Peroral Drug Delivery: 36

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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. Drug Delivery In The Oral Cavity: 37

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Drug Delivery in the G.I.T: Ease of administration of drugs. Availability of large surface area for drug absorption High patient compliance. First pass metabolism. Pre-systemic metabolism. Advantages with oral route Drawbacks with oral route 38

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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. 39

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Ocular Delivery : 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 efficacy. Drawbacks with ocular route 40

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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. Hydrogels in Ocular Delivery 41

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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. Hydrogels in Ocular Delivery 42

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Ocular Delivery : Swollen Hydrogels can deliver drugs for long duration. Easy to remove. Patient compliance is high. Advantages 43

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Transdermal Delivery : 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. Purpose 44

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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. 45

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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. 46

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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. 47

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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. 48

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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. 49

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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. 50

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Hydrogels To Fix Bone Replacements: Coating materials. Ex: Methacrylate , Hyaluronic acid esters. Replacements made of stainless steel, metal alloys, titanium, or cobalt-chromium, can be coated with these materials 51

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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. 52

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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. 53

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Topical Drug Delivery: Antifungal formulations like Cotrimazole has been developed as Hydrogel formulation for vaginitis and shows better absorption than conventional cream formulations. 54

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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 55

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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 56

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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. 57

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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. 58

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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. 59

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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. 60

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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. 61

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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. 62

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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. 63

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Thank You 64

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