CONTROLLED DRUG DELIVERY SYSTEMS

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CONTROLLED DRUG DELIVERY SYSTEMS

  1. 1. 1
  2. 2. Controlled release• To achieve prolong therapeutic effect.• Implies predictability in drug release kinetics.• Deliver the drug at pre determined rate, locally or systematically. 2
  3. 3. Advantages• Improve patient convenience.• Reduction in fluctuation in steady state level.• Increase the safety margin of high potency drug.• Reduction in total health care cost. 3
  4. 4. Disadvantages• Decrease systemic availability.• Poor invitro – invivo correlation.• Increased risk of toxicity.• Retrieval of drug is difficult in case of toxicity , poisoning or hyper sensitivity reaction. 4
  5. 5. Classification of rate controlled drug delivery system1. Rate preprogrammed drug delivery system.2. Activation modulated drug delivery system.3. Feed back regulated drug delivery system.4. Site targeting drug delivery system. 5
  6. 6. Rate preprogrammed drug delivery system 6
  7. 7. 7
  8. 8. Rate programmed DDS• The release of drug molecules from delivery system has been programmed at specific rate profile.• It control molecular diffusion of drug molecules in or across barrier medium within or surrounding the delivery system. 8
  9. 9. These system can be further classified as follow1. Polymer membrane permeation CDDS.2. Polymer matrix diffusion CDDS.3. Micro reservoir partition CDDS. 9
  10. 10. 1. Polymer membrane permeation CDDS• Drug formulation totally or partially encapsulated within drug reservoir compartment.• Its drug release surface is covered by a rate controlling polymeric membrane.• The encapsulation of drug formulation is carried out by spray coating, micro encapsulation or other technique. 10
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  13. 13. The rate of drug release Q/t should be constant value and define asKm/r & Ka/m = partition co efficient for drug moleculefrom reservoir to membrane and from membrane tosurrounding aqueous layer respectively. 13
  14. 14. Dd & Dm =Diffusion coefficient in the aqueous diffusion layer and in the rate controlling membrane respectively.CR = drug concentration in reservoir compartment. 14
  15. 15. a). Progestreat IUDDrug – suspension of progesterone crystals in silicone medical fluid.Rate controlling membrane – Non porous membrane of ethylene vinyl acetate copolymer.Release rate – 65mcg/day 15
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  17. 17. b). occusertDrug – pilocarpine alginate complex.Rate controlling membrane – micro porous ethylene vinyl acetate co polymer.Release rate – 20-40 mcg/hr 17
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  19. 19. 2.Polymer matrix diffusion CDDS•Prepared by homogenously dispersing drug particles inrate controlling polymer matrix.•Lipophilic or hydrophilic polymers are used.•The drug dispersion in the polymer matrix is carriedout by 1.Blending of drug with liquid polymer. 2.Mixing of drug with a rubbery polymer. 19
  20. 20. Drug release from polymer matrix carried out as a homogenous dispersion ina). Lipophilic, nonswellable polymer matrix.b). Hydrophilic, swellable polymer matrix. 20
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  22. 22. The rate of the drug release is define as A = Initial drug loading dose. CR = Drug solubility in polymer. DP = Diffusivity in the polymer matrix. 22
  23. 23. a). Nitro - Dur• Nitroglycerin containing matrix system.• It is fabricated by first heating in a aqueous solution of aqueous soluble polymer, glycerol and poly vinyl alcohol.• The temperature of solution is gradually lowered and nitroglycerin and lactose triturate are disperse just above the congealing temperature of solution.• The mixture is solidified in a mold at or below room temperature and than sliced to form a medicated polymer disc. 23
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  25. 25. The release rate can be define asKa/r = partition coefficient of drug from reservoir to adhesive layer.ha = thickness of adhesive layer.Da = diffusion coefficient in aqueous layer. 25
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  27. 27. 3. Micro reservoir partition CDDS• Fabricated by micro dispersion of an aqueoussuspension of drug in a bio compatible polymer.• The rate of release is define asn = ratio of drug concentration at the inner edge of inter-facial barrier over drug solubility in polymer matrix.m = a/ba = ratio of drug concentration in the bulk of elutionsolution over drug solubility in the same mecdium. 27
  28. 28. b = ratio of drug concentration at the outer edge of the polymer coating membrane over drug solubility in same polymer.Kl , Km, Kp = Partition coefficient of drug from liquidcompartment to polymer matrix, from polymer matrix topolymer coating membrane, from polymer coatingmembrane to elution solution respectively.D1, Dp, Dd = Diffusivities of drug in the lipid layersurrounding polymer coating membrane with thicknessh1,hp,hd.S1,Sp = solubilities of drug in the liquid compartment andin the polymer matrix respectively. 28
  29. 29. a). Nitro disc system•Preparation : Nitroglycerine + lactose 40% polyethylene glycol 400 Isopropyl palminate Silicone elastomer Moulded to form solid medicated disc. 29
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  31. 31. b). Subdermal syncro-Mate-C implantDrug reservoir – Norgestomet in aqueous solution of PEG400. 31
  32. 32. Feedback regulated drug delivery system 32
  33. 33. Feedback regulated drug delivery system• In this system release of drug molecule from delivery system activated by a triggering agent.. 33
  34. 34. Feedback regulated DDS is classified as follow 1.Bioerosion regulated DDS. 2.Bioresponsive DDS. 3.Self regulated DDS. 34
  35. 35. 1. Bioerosion regulated DDSSystem consist of drugdispersed bioerodiblematrix fabricated frompoly (vinyl methyl ester)half ester. which is coatedwith a layer ofimmobilized urease. 35
  36. 36. 2. Bioresponsive DDSIn this system the drug reservoir is contained in adevice enclosed by a bio responsive polymericmembrane whose drug permeability is controlled byconcentration of a bio chemical agent in the tissuewhere the system is located. 36
  37. 37. 37
  38. 38. 3. Self regulating DDS• This system depend on a reversible and competitive binding mechanism to activate and to regulate the drug release. 38
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  40. 40. References• Biopharmaceutics And Pharmacokinetics - DM. Brahmankar, Sunil. B.Jaiswal.• Novel drug delivery system Y.W.Chien• Google.com 40
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