Hydrogels methacrylate were prepared for the pulsatile delivery

Hydrogels that areresponsive to both temperature and ph can be made simply incorporatingionisable and hydrophobic functional groups to the same hydrogels. When a smallamount of anionic monomer such as acrylic acid is incorporated in athermoreversible polymer, the LCST of the hydrogel depends on the ionization ofpendant carboxyl groups.

As the ph of the medium increases above the pka ofcarboxyl groups of the polyanions, the LCST shifts to higher temperatures dueto the increased hydrophilicity and charge repulsion. Terpolymer hydrogelscontaining NIPPAAm, acrylic acid and 2-hydroxyethyl methacrylate were preparedfor the pulsatile delivery of streptokinase and heparin as a function ofstepwise ph and temperature changes.OtherApplications Phsensitive hydrogels have been used in making biosensors and permeationswitches, the ph sensitive hydrogels for these applications are loaded withenzymes that change the local microenvironment inside the hydrogels. One of theenzymes used is glucose oxidase that transforms glucose into gluconic acid. Theformation of gluconic acid lowers the local ph, thus affecting the swelling ofph sensitive hydrogels.Limitationsand ImprovementsOne of thelimitations of synthetic ph sensitive polymers is non-biodegradability. Forthis reason polymers made up of non-biodegradable polymers are removed frombody after use. The non-biodegradability is not a problem in certainapplications such as in oral drug delivery but it becomes a serious limitationin other applications such as the development of implantable drug attention hasbeen focused on the development of biodegradable, ph sensitive hydrogels basedon peptides, proteins and polysaccharides.

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Dextran wasactivated with 4-aminobutyric acid for crosslinking with 1, 10 diaminodecaneand also grafted with carboxylic groups. The modified dextran hydrogels showeda faster and higher degree of swelling at high ph conditions and changing theph between 7 and 2 resulted in cyclic swelling-deswelling. It is noted that thedextran hydrogels may not be exactly biodegradable, since the body or certainsites in body may not have the enzyme to degrade dextran molecules. The naturalpolysaccharides are not usually biodegradable in human body.Syntheticpolypeptides are also used in the synthesis of biodegradable hydrogels becauseof their more regular arrangement and less versatile amino acid residues thanthose derived from the natural proteins. Example of such synthetic polypeptidehydrogels include poly aspartic acid poly L-lysine and poly glutamic acid.Entericcoated systemsEnteric-coatedformulations are suitable vehicles to modify the release of active substancessuch that release at specific target areas in the gastrointestinal tract andpreventing its release in stomach.

The major aim of enteric coating is theprotection of drugs that are sensitive or unstable at acidic ph. This isparticularly important for drugs such as enzymes and proteins because thesemacromolecules are rapidly hydrolyzed and inactivated in acidic medium.Macrolide antibiotics such as erythromycin are rapidly degraded by gastricjuices. Acidic drugs like NSAID’s are also enteric coated to prevent localirritation of the mucosa.Anotherpurpose of enteric coating is drug targeting as in case of 5-aminosalicylicacid or the prodrugs sulfasalazine.

In these cases, enteric coating is appliedsuch that the drug concentration is increased in the lower parts of the GITract. Although the use of enteric coating to achieve modified drug release isknown for long but it has always been criticized as to its true value ofproviding protection and targeted release of coated active agents.DosageFormsIn general,film coated dosage forms can be divided into two forms multiple unit and singleunit dosage forms. Single unit dosage form contains tablets, film coatedcapsules and other forms. Multiple units contains granules, capsules, pelletsand compressed film coated particles.

   Advantages Following are theadvantages1.       Drug directly available at the target site2.       Decreased dose to be administered3.       Decreased side effects4.       Improved drug utilization5.       Improved patient compliance6.

       Lower daily cost to the patient due tofewer dosage units are required by the patient in therapy7.       Protection of mucosa from irritating drugs8.       Drug loss is prevented by extensive drugpass metabolism   Example of noveldrugsPH-sensitive hydrogels based on polyethylene glycol andmethacrylic acid (MAA) macromonomer (PEGMEMA) entrapping diliazem HCL weresynthesized inside soft gelatin capsules for use as a new dosage form for oraladministration of drug. for the evaluation of their swelling and releasebehaviour in two media, different monomers were used:  at ph 7 stimulating the higher ph environmentof the intestine while at low ph stimulating the acid ph of the stomach. Boththe processes DIL-HCL release and swelling are dependant on Ph and compositionof monomer. Hydrogels with intermediate compositions showed diminished DIL·HClrelease at pH 1.

2. Similar shaped release profiles were found for the fourhydrogels compositions at ph 7. At this neutral ph slow protonation of thecarboxylate groups of MAA led to the swelling front and a dry core that isobserved by MRI. As a result of this swelling, release curves exhibited a longperiod of zero order kinetics.

So, this shows that the system could be asuitable candidate for developing a zero order release dosage form for oraladministration of DIL-HCL. The dissolution and swelling processes were analysedby different mathematical approaches.2) the development of a novel colon-specific drug delivery system withmethacrylate derivatives of 5-ASA using drug release properties and PHsensitive swelling. 5-ASA film coated tablets were prepared for colon specificdelivery.

During this method 5-ASA core tablets were first prepared then coatedwith dispersion containing Eudragit RS and dessterrifed pectin,polygalacturonicacidor its sodium and potassium salts. Negligible drug releaseoccurred during the first five hours where the coated tablets were in smallintestine and stomach. After that, the release of 5-ASA from coated tabletsoccurred linearly as a function of time because of the action of pectinolyticenzymes.   http://ijpsr.com/bft-article/novel-colon-specific-drug-delivery-system-a-review/?view=fulltexthttp://www.sciencedirect.com/science/article/pii/S1742706110003375  

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