Controlled release oral drug delivery

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Controlled release oral drug delivery

  1. 1. Controlled Release Oral Drug Delivery System
  2. 2. Contents  Overview of Digestive system  Introduction  Advantages  Disadvantages  Mechanisms 1.Dissolution 2.Diffusion 3.Combination of Dissolution & Diffusion 4.Osmotic pressure controlled system  References2 04/30/2010
  3. 3. Digestive System3 04/30/2010
  4. 4. Concept  Controlled drug delivery is one which delivers the drug at a predetermined rate, for locally or systemically, for a specified period of time.  Continuous oral delivery of drugs at predictable & reproducible kinetics for predetermined period throughout the course of GIT.4 04/30/2010
  5. 5. Plasma concentration time profile5 04/30/2010
  6. 6. Challenges in Oral DrugDelivery  Development of drug delivery system Delivering a drug at therapeutically effective rate to desirable site.  Modulation of GI transit time Transportation of drug to target site.  Minimization of first pass elimination6 04/30/2010
  7. 7. Advantages  Total dose is low.  Reduced GI side effects.  Reduced dosing frequency.  Better patient acceptance and compliance.  Less fluctuation at plasma drug levels.  More uniform drug effect  Improved efficacy/safety ratio.7 04/30/2010
  8. 8. Disadvantages  Dose dumping.  Reduced potential for accurate dose adjustment.  Need of additional patient education.  Stability problem.8 04/30/2010
  9. 9. Mechanism aspects of Oral drug delivery formulation 1.Dissolution : 1.Matrix 2.Encapsulation 2.Diffusion : 1.Matrix 2.Reservoir 3.Combination of both dissolution & diffusion. 4.Osmotic pressure controlled system9 04/30/2010
  10. 10. Dissolution Definition:  Solid substances solubilizes in a given solvent.  Mass transfer from solid to liquid.  Rate determining step: Diffusion from solid to liquid.  Several theories to explain dissolution – Diffusion layer theory (imp) Surface renewal theory Limited solvation theory.10 04/30/2010
  11. 11. Noyes Whitney Equation dc/dt = kD.A (Cs – C ) dc/dt = D/h A. (Cs – C) dc/dt = Dissolution rate. k= Dissolution rate constant (1st order). D = Diffusion coefficient/diffusivity Cs = Saturation/ maximum drug solubility. C =Con. Of drug in bulk solution. Cs-C=concentration gradient. h =Thickness of diffusion layer.11 04/30/2010
  12. 12. Matrix Type  Also called as Monolith dissolution controlled system. Soluble drug  Controlled dissolution by: 1.Altering porosity of tablet. 2.Decreasing its wettebility. 3.Dissolving at slower rate. Slowly  First order drug release. dissolving matrix  Drug release determined by dissolution rate of polymer.  Examples: Dimetane extencaps, Dimetapp extentabs.12 04/30/2010
  13. 13. Encapsulation Called as Coating dissolution controlled system. Dissolution rate of coat depends Soluble drug upon stability & thickness of coating. Masks colour,odour,taste,minimising GI irritation. Slowly dissolving One of the microencapsulation or erodible method is used. coat Examples: Ornade spansules, Chlortrimeton Repetabs13 04/30/2010
  14. 14. Diffusion  Major process for absorption.  No energy required.  Drug molecules diffuse from a region of higher concentration to lower concentration until equilibrium is attainded.  Directly proportional to the concentration gradient across the membrane.14 04/30/2010
  15. 15. Matrix Diffusion Types  Rigid Matrix Diffusion Materials used are insoluble plastics such as PVP & fatty acids.  Swellable Matrix Diffusion 1. Also called as Glassy hydrogels.Popular for sustaining the release of highly water soluble drugs. 2. Materials used are hydrophilic gums. Examples : Natural- Guar gum,Tragacanth. Semisynthetic -HPMC,CMC,Xanthum gum. Synthetic -Polyacrilamides. Examples: Glucotrol XL, Procardia XL15 04/30/2010
  16. 16. Matrix system Rate controlling step: Diffusion of dissolved drug in matrix.16 04/30/2010
  17. 17. Higuchi Equation Q = DE/T (2A.E Cs)Cs.t)1/2Where , Q=amt of drug release per unit surface area at time t. D=diffusion coefficient of drug in the release medium. E=porosity of matrix. Cs=solubility of drug in release medium. T=tortuosity of matrix. A=concentration of drug present in matrix per unit volume.17 04/30/2010
  18. 18. Reservoir System  Also called as Laminated matrix device.  Hollow system containing an inner core surrounded in water insoluble membrane.  Polymer can be applied by coating or micro encapsulation.  Rate controlling mechanism - partitioning into membrane with subsequent release into surrounding fluid by diffusion.  Commonly used polymers - HPC, ethyl cellulose & polyvinyl acetate.  Examples: Nico-400, Nitro-Bid18 04/30/2010
  19. 19. Reservoir System Rate controlling steps : Polymeric content in coating, thickness of coating, hardness of microcapsule.19 04/30/2010
  20. 20. Dissolution & Diffusion Controlled Release system  Drug encased in a partially soluble membrane.  Pores are created due to dissolution Insoluble membrane of parts of membrane. Entry of  It permits entry of aqueous medium dissolution into core & drug dissolution. fluid  Diffusion of dissolved drug out of Drug system. diffusion  Ex- Ethyl cellulose & PVP mixture Pore created by dissolves in water & create pores of dissolution of insoluble ethyl cellulose membrane. soluble fraction of membrane20 04/30/2010
  21. 21. Osmotic Pressure Controlled Drug Delivery System  Definition  Procedure  Diagram  Modifications21 04/30/2010
  22. 22. Osmosis - Movement of solvent from lower to higher concentration.  - The passage of solvent into a solution through semipermeable membrane. Semipermeable Membrane  Molecules are permitted only to one component (Water). Osmotic pressure  It is the hydrostatic pressure produced by a solution in a space divided by a semipermeable membrane due to difference in concentration of solutes.22 04/30/2010
  23. 23. Osmotic Pressure Controlled System  Provides zero order release  Drug may be osmotically active, or combined with an osmotically active salt (e.g., NaCl).  Semipermeable membrane usually made from cellulose acetate.  More suitable for hydrophilic drug.  Examples: Glucotrol XL, Procardia XL,23 04/30/2010
  24. 24. Equation (Q/t) z = Pw Am/ hm (πs-πe ) (Q/t)= Rate of zero order drug release. Pw, Am & hm= water permeability, effective surface area & thickness of semipermeable membrane. πs= osmotic pressure of saturated solution of osmotically active drug or salt in system. πe = osmotic pressure of GI fluid.24 04/30/2010
  25. 25. Osmotic Pressure Controlled System25 04/30/2010
  26. 26. Osmotic Pressure Controlled System26 04/30/2010
  27. 27. Modifications- Immediate release system.- Osmotically active compartment system
  28. 28. Immediate Release System  Activation of system is done.  Dividing a dose into two parts.  One third immediate release.  Two third controlled release.  Encapsulated into semipermeable membrane. e.g. : Phenyl propanolamine.28 04/30/2010
  29. 29. Osmotically active system  Two compartments Delivery orifice separated by movable partition.  Osmotically active Drug compartment compartment absorbs Movable partition water from GIT. Osmotically active  Creates osmotic compartment pressure.  Partition moves upward & then drug releases.  Ex: Nifedipine.29 04/30/2010
  30. 30. Some Popular Brand names used for OCDDS  Spansule capsule ( SK & F )  Sequal capsule (Lederle )  Extentab tablets ( Robins )  Timespan tablet ( Roche )  Dospan tablet ( Merrell Dow )  Chronotab tablet ( Schering )  Plateau capsule ( Marion )  Tempule capsule ( Armour )30 04/30/2010
  31. 31. Some Examples of OCDDS  Propranolol (Inderal LA)  Methyiphenidate HCl (RitalinSR)  Iron (Slow-Fe)  GITS-Prazosin (Minipress)  Morphine sulfate (Roxanol SR)  Decongestant & antihistamine (Resaid SR, Novafed SR Dristan)  Pseudoephedrine HCI (Sudafed SA)  Potassium (Micro-K, Slow-K, Klotrix)  Antitussive combinations (Rescap, Ornade Spansules)  Chlorpheniramine maleate (ChlorTrimeton)  Decongestant, antihistamine and anticholinergic (Dallergy, Supres)31 04/30/2010
  32. 32. Recent Trends : Extended release formulation of Bupropion  Bupropion is used in the treatment of major depressive disorder.  Conventional formulation has to be administered 3 times daily  Initially 150 mg ER formulation was introduced for bid regimen Later on 300 mg ER formulation was introduced for once daily regimen  For ER formulation provide similar Cmax and AUC values as compared to immediate release formulation at steady state.32 04/30/2010
  33. 33. Recent Trends : Extended release formulation of Bupropion33 04/30/2010
  34. 34. Recent Trends: OROS Technology (ALZA corporation) ELEMENTARY OSMOTIC PUMP Single layer tablet: Drug core (water soluble drug with or without excipients) Semipermeable membrane with a drilled orifice Water imbibition by the core because of osmotic action results in drug dissolution, which is released at a controlled rate through the orifice Not suitable for water insoluble drugs. Examples: Sudafed 24 hours (Pseudoephedrine); Volmax (Salbutamol)34 04/30/2010
  35. 35. Recent trends: Geomatrix® (SKY Parma) Products in market: Cordicant -uno® Madopar DR SULAR ER This technology Controls amount, timing and location of release in body. -Formulation with predictable and reproducible drug release profile. -Controls rate of drug diffusion throughout release process, ensuring 100% release Products35 04/30/2010
  36. 36. References  Novel drug delivery system , volume 50, Y.W.Chien  The theory & practice of industrial pharmacy, Leon Lachman , Herbert A.Lieberman, Joseph L.Kanig,3 rd edition.  The Eastern pharmacist, november 1993. Sustained release drugs, V R.Gudsoorkar & D.Rambhau page 27-32  Biopharmaceuitics & pharmacokinetics, D M.Brahmankar & Sunil B. Jaiswal. www.google.com36 04/30/2010
  37. 37. Thank you for listening me………37 04/30/2010

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