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GASTRORETENTIVE DRUG DELIVERY SYSTEMS Presented By : Akash Aher (M.pharm -2 nd semester) Guided by : Dr.G.S Asane (Dept. of pharmaceutics)
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1 gastroretentive drug delivery systems

Dec 05, 2014

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  • 1. Presented By : Akash Aher(M.pharm -2nd semester)Guided by : Dr.G.S Asane(Dept. of pharmaceutics)

2. Contents Introduction Need of Gastric retention Advantages Limitation Physiology of Stomach Approaches of Gastric retention Evaluation of GRDDS Conclusion 3. Introduction Oral drug administration has been the predominantroute for drug delivery. Gastric residence time is time which a drug resides instomach. Depends upon fluid and food intake. GRDDS are designed to delay gastric emptying. 4. Gastro retention is done for: Drugs that absorb from stomach (Levodopa, Furosemide). Acting locally in stomach (Antacids, Antiulcer andEnzymes). Antibiotic therapy. Poorly soluble at alkaline pH.( Diazepam, Salbutamol) Degrade in colon. (Captopril, Ranitidine, Metronidazole) Narrow window of absorption 5. Fig.no-1 6. Gastric retention is unsuitable for: Drugs having limited acid solubility. (Phenytoin) Instable in gastric conditions. ( Erythromycin) Extensive first pass metabolism.Factors affecting gastric retention of dosage forms Density Size Shape 7. Advantages Improved drug absorption, because of increased GRT andmore time spent by the dosage form at its absorption site. Controlled delivery of drugs. Minimizing mucosal irritation by releasing drugs slowly ata controlled rate. Treatment of gastrointestinal disorders such as gastro-esophageal reflux, providing local action. Ease of administration and better patient compliance. 8. Limitations- Retention in the stomach is not desirable for drugs that causegastric lesions (e.g. Non- steroidal anti-inflammatory drugsNSAIDs). Drugs that are degraded in acidic environment of stomach(e.g. Insulin). Drugs that undergo a significant first-pass metabolism (e.g.Nifedipine). Drugs that have very limited acid solubility (e.g. Phenytoin). 9. Review of Stomach & GITA tube about nine meters long that runs through the middle ofthe body from the mouth to the anus and includes ; throat (pharynx), esophagus, stomach, small intestine- duodenum- jejunum- ileum large intestine .Fig.no-2 10. Gastrointestinal dynamics These are the fourmotility phases withinthe stomach duringfasting stage. The dosage form shouldbe capable of withstanding the housekeeping action ofphase III. 11. Approaches for gastric retention Floating drug delivery systems Mucoadhesive systems Swellable Systems High density systems.Fig.no-3 12. Fig.no-4 13. Floating drug delivery systems These are low density systems. Have ability to float over gastric contents. The drug is must have sufficient structure to form a cohesivegel barrier. It must maintain an overall specific gravity lower than that ofgastric contents (1.004 1.010). eased from the system at desired rate. 14. Floating Techniques Effervescent Volatile liquid containing systems Gas generating systems Non-Effervescent Colloidal gel barrier systems Alginate beads Hollow Microspheres Microporous Compartment System 15. Effervescent systems1.Gas generating systems Effervescence is there. Utilizes effervescent reactions betweencarbonate/bicarbonate salts and citric/tartaric acid. CO2 is released in presence of H2O. When tablet is put in beaker it will sink 2NaHCO3+C4H6O6 C4H4Na2O6+2CO2+2H2O With production of gas it rises up and floats. 16. 2. Volatile liquid containing systems Incorporates an inflatable chamber, which contains a liquide.g. ether, cyclopentane, that gasifies at body temperature tocause the inflatation of the chamber in the stomach. The device may also consist of a bioerodible plug made upof PVA, Polyethylene, etc. that gradually dissolves causingthe inflatable chamber to release gas and collapse after apredetermined time to permit the spontaneous ejection ofthe inflatable systems from the stomach. There systems are very less used as the gas generatingsystems are more safe. 17. Non-effervescent systems1. Colloidal gel barrier systems Such systems contains drug with gel forming hydrocolloidsmeant to remain buoyant on stomach contents. These systems incorporate a high level of one or more gelforming highly Swellable cellulose type hydrocolloids.e.g.HEC, HPMC, NaCMC. On coming in contact with gastric fluids forms a viscous core. Incorporates H2O and entraps air. Density of system falls below 1gm/cm3. Then it starts floatingFig.no-5 18. 2. Microporous membrane systems Based on the encapsulation of drug reservoir inside aMicroporous compartment. The peripheral walls of the drug reservoir compartment arecompletely sealed to prevent any direct contact of the gastricmucosal surface with the undissolved drug. In stomach the floatation chamber containing entrapped aircauses the delivery system to float over the gastric contents. Gastric fluid enters through the apertures, dissolves thedrug, and carries the dissolve drug for absorption. 19. 3. Alginate beads Spherical beads of approximately 2.5 mm in diameter can beprepared by dropping a sodium alginate solution in toaqueous solutions of calcium chloride, causing precipitationof calcium alginate. Sodium alginate+ Calcium chloride Calcium alginate+NaCl The beads are then separated snap and frozen in liquidnitrogen, and freeze dried at -40C for 24 hours, leading to theformation of porous system. Maintain a floating force of over 12 hours. 20. 4. Hollow microspheres Microballoons / hollow microspheres loaded with drugsare prepared by simple solvent evaporation method. Commonly used polymers to develop these systems arepolycarbonate, cellulose acetate, calciumalginate, Eudragit S, agar and pectin etc. These systems have capacity to float on acidic dissolutionmedia containing surfactant for about 12 hours invitro. 21. ContFig.no-6 22. Mucoadhesive systems Involves the use of bioadhesive polymers, which can adhereto the epithelial surface in the stomach. Dosage form can stick to mucosal surface by followingmechanisms:1. The wetting theory2. The diffusion theory3. The absorption theory4. The electron theory 23. Swellable systems A dosage form in the stomach will withstand gastric transit ifit bigger than pyloric sphincter, but should be small enoughto be swallowed. These systems swells many times its original size. Cross linking should be optimum highly cross linked dontswell. Chitosan, HPMC, sodium starch glycolate, carbopol are used. Diclofenac, Ciprofloxacin, Furosemide are reported withthese systems. 24. Fig.no-7 25. High density systems These have density greater than that of gastric fluids (1.4g/cc). Above 1.6g/cc is preferable, tend to withstand peristalticmovements of stomach. Zinc oxide, Iron oxide, Titanium dioxide, barium sulfate areused as inert heavy core.Fig.no-8 26. Evaluation of GRDDSFloating drug delivery systemsFloating time Determined by using the USP dissolution apparatuscontaining 900 ml of 0.1 N HCL maintained at 37o C. The time for which the dosage form floats is termedas the floating time.Specific Gravity / Density Density can be determined by the displacementmethod using Benzene as displacement medium 27. Muco Adhesion system Measurement of either tensile or shear strength is the mostcommonly used invitro method to measure bioadhesionstrength. Measurement of tensile strength involves quantiting the forcerequired to break the adhesion bond between the testpolymer and model membrane. The method typically uses modified balance or tensile tester 28. Bioadhesion strength measurementForce measuringdeviceUpper jawPolymerLower jawMembraneFig.no-9 29. Swelling systemsWeight gain and water uptake Done by immersing the dosage in simulated gastric fluidat 37oC and determining these factors at regular intervals. Dimensional changes can be measured in terms ofincrease in the tablet diameter or thickness with time. Water uptake is measured in terms of %weight gain 30. WU = (Wt-Wo) X 100WoWhere WU Water uptakeWt weight of dosage form at time tWo weight of dosage form initially 31. Commercial GastroretentiveFormulation 32. ConclusionGastro retentive drug delivery systems are the mostpreferable systems in order to deliver the drugs whichhave a narrow absorption window near the gastricregion. Now a days a number of drug delivery devicesare being developed which aim at releasing the drug atgastric region. Even though these drug delivery systemshave several advantages they also have disadvantageslike their invitro invivo correlation is very less. 33. References Doshi S.M., Tank H.M., Gastro Retention AnInnovation over Conventional poorly Soluble Drugs : Areview, International Journal of Pharmaceutical andchemcal Sciences, 2012;1(2):859-866. S. P. Vyas, Roop K. Khar, CONTROLLED DRUGDELIVERY Concepts & Advances, VallabhPrakashan, page no. 196-217. N. K. Jain, Progress in Controlled & Novel Drug DeliverySystems, 1st edition 2004, CBS Publishers, page no.76-97 Chien Yie W. Novel drug delivery systems, Vol-50, 2nded, Marcel Dekker . Inc, New York. Pg No.164-177. 34. Anand S. Surana & Rakhee K. Kotecha, Anovervew on various approaches to oral controlled drugdelivery system via gastroretention IJPSRR, Vol-2, May-June 2010. pp: 68-72 Shweta A, Javed A, Alka A, Roop K, and Sanjula B.Floating drug delivery systems: a review. AAPSPharmSciTech. 2005;6 (3) Article 47. Ecyclopedia of Pharmaceutical Technology. International Journal of Research in Pharmaceuticaland Biomedical Sciences ISSN: 2229-3701 35. G. Chawla, P. Gupta, V. Koradia, A. K.Bansal, Pharmaceutical TechnologyJuly 2003, 50-68 Arora Shweta, Ali Javed, Ahuja Alka, Khar Roopand Baboota Sanjula. Floating drug deliverysystem; A Review. AAPS PharmaSciTech. 2005, 6(3), E372-E390. Singh N. Brahma and Kim H. Kwon. Floatingdrug delivery systems; An approach to oralcontrolled drug delivery via gastric retention. J.Controlled Release. 2000, 63, 235-25 Nayak Amit, Maji Ruma and Das Biswarup. Gastroretentive drug delivery system; Review. Asian. J.Pharm. Res. 2010, 3, 2-10.