Rate controlled drug delivery by using rate preprogrammed drug delivery systems

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Rate controlled drug delivery by using rate preprogrammed drug delivery systems

  1. 1. SEMINAR ONRATE- CONTROLLED DRUGDELIVERY BY USING RATE-PREPROGRAMMED DRUGDELIVERY SYSTEMSPRESENTED BY:GANDHI SONAM MUKESHCHANDRA
  2. 2. INTRODUCTION Conventional drug delivery systems (DDS) 2
  3. 3. Sustained release and controlled release DDS 70 60 50 40 Solution Dexatrim 30 Acutrim 20 10 0 0 5 10 15 20 25 30 3
  4. 4. CLASSIFICATION Rate- preprogrammed drug delivery systems Activation – modulated drug delivery systems Feedback- regulated drug delivery systems Site- targeting drug delivery systems 4
  5. 5. RATE- PREPROGRAMMED DDS Release of drug molecules from the delivery systems has been preprogrammed at specific rate profiles Diffusion of drug molecules into the medium is controlledCLASSIFICATION OF RATE- PREPROGRAMMED DDSA. Polymer membrane permeation-controlled drug delivery systemsB. Polymer matrix diffusion-controlled drug delivery systemsC. Micro reservoir partition-controlled drug delivery systems 5
  6. 6. A. POLYMER MEMBRANE PERMEATION-CONTROLLED DDS Drug release surface of the reservoir compartment is rate- controlling polymeric membrane. Polymeric membrane can be nonporous, microporous or semi permeable in nature. Encapsulation of drug in the reservoir is accomplished by injection molding, spray coating, capsulation or microencapsulation. Q/t = [(Km/r Ka/m Dd Dm)/( Km/r Dm hd + Ka/m Dd hm)] cR 6
  7. 7.  Release of drug is controlled by controlling the partition coefficient and diffusivity of the drug molecule and the thickness of the rate-controlling membraneEXAMPLESPROGESTASERT IUD: reservoir - suspension of progesterone crystals in silicone medical fluid Membrane- nonporous membrane of ethylene vinyl acetate copolymer Deliver natural progesterone continuously in the uterine cavity at a daily dosage rate of at least 65 µg/day to achieve contraception for1 year. 7
  8. 8. PROGESTASERT 8
  9. 9. OCUSERT SYSTEM thin disk of pilocarpine alginate complex sandwiched between two transparent sheets of microporous ethylene- vinyl acetate copolymer membrane. 9
  10. 10.  Either 20 or 40 µg/hr of pilocarpine is releasedTRANSDERM-NITRO Nitroglycerin-lactose triturate in the silicone medical fluid Micro porous membrane of ethylene-vinyl acetate copolymer Thin layer of pressure-sensitive silicone adhesive polymer is coated 10
  11. 11. B. POLYMER MATRIX DIFFUSION-CONTROLLED DDS Reservoir is prepared by homogenously dispersing drug particles in a rate-controlling polymer matrix. 11
  12. 12.  Q/t1/2 = (2ACRDp)1/2 release of drug is controlled by controlling the loading dose, polymer solubility of the drug, and its diffusivity in the polymer matrixEXAMPLESNITRO-DUR Nitro-glycerine transdermal patch for 24 hr to provide a continuous transdermal infusion of nitro-glycerine at a dosage rate of 0.5 mg/cm2/day for the treatment of angina pectoris. 12
  13. 13. NITRO-DUR 13
  14. 14. C. MICRORESERVOIR PARTITION- CONTROLLED DRUG DELIVERY SYSTEMS Micro dispersion of an aqueous suspension of drug using a high- energy dispersion technique in a bio-compatible polymer,(Eg. silicone elastomers), forms a homogenous dispersion of many discrete, unleachable, microscopic drug reservoirs. device can be further coated with a layer of biocompatible polymer to modify the mechanism and the rate of drug release 14
  15. 15.  Release of drug molecules from this type of CRDDS can follow either dissolution or a matrix diffusion-controlled process depending upon the relative magnitude of Sl and SpEXAMPLESNITRODISC SYSTEM Nitro-glycerine in silicone elastomer 0.5mg/cm2 for once-a-day 15
  16. 16. ACTIVATION MODULATED DDS Drug delivery is activated and controlled by physical, chemical or bio- chemical processes or facilitated by the energy supplied externallyClassification of activation modulated DDS Based on the nature of the process applied or the type of energy used1. Physical means2. Chemical means3. Biological means 16
  17. 17. DDS activated by physical meansa. Osmotic pressure- activated DDSb. Hydrodynamic pressure activated DDSc. Vapour pressure activated DDSd. Mechanically activated DDSe. Magnetically activated DDSf. Sonophorosis activated DDSg. Iontophoresis activated DDSh. Hydration activated DDS 17
  18. 18. 1. Osmotic pressure- activated DDS drug reservoir can be a solution contained within an impermeable collapsable tube. This is covered with osmotic agent place in a rigid semi permeable housing with controlled water permeability. The rate of drug release is modulated by the gradient of osmotic pressure. Q/t = PwAm (πs-πe) /hmPw = water permeabilityAm = effective surface areahm =thickness of the semi permeable housing 18
  19. 19. Vasopressin 19
  20. 20. 2. Hydrodynamic pressure activated DDS hydrodynamic pressure is used as the source of energy to activate the drug release. 20
  21. 21. Q/t = Pf Am/hm (θs – θe)Pf = fluid permeabilityAm = effective surface areahm = thickness of the wall with annular openingsθs – θe = difference in hydrodynamic pressure between the DDS and the environment 21
  22. 22. 3. Vapour pressure- activated drug delivery systems Drug inside infusion compartment is separated from pumping compartment by freely movable partition. Pumping compartment contains a fluorocarbon fluid that vaporizes at body temperature The vapour pressure created moves the partition upward, forcing the drug to be delivered. Eg: INFUSAID implants (heparin) 22
  23. 23. 1. Flow regulator, 2. silicone polymer coating, 3. patrition,4. Pumping compartment, 5. Infusate compartment, 6. fluorocarbonfluid filling tube, 7. filter assembly, 8. inlet septum for percutaneousrefill of infusate, 9. needle stop. 23
  24. 24. Q/t= d4(Ps-P-e)/40.74µld & l = the inner diameter and the length of the delivery cannula, respectivelyPs-P-e = difference between the vapour pressure in the pumping compartment and the site of implantation.µ = viscosity of the drug formulation used. 24
  25. 25. 4. Mechanically activated drug delivery system Equipped with a mechanically activated pumping system A measured dose of drug formulation is reproducibly delivered The volume of solution delivered is controllable, as small as 10- 100µl Volume of solution delivered is independent of the force & duration of activation applied as well as the solution volume in the container. Example is the development of metered dose nebulizer for the intranasal administration of a precision dose of buserelin (LHRH). 25
  26. 26. 26
  27. 27. 5. Magnetically activated drug delivery systems Drug reservoir is a dispersion of peptide or protein powders in a polymer matrix Low rate of delivery is improved by incorporating electromagnetically triggered vibration mechanism 27
  28. 28.  Coating polymer can be a ethylene-vinyl acetate copolymer or silicon elastomers. These systems have been used to deliver protein drugs, such as bovine serum albumin6. Sonophoresis-activated drug delivery systems Utilize ultrasonic energy to activate the delivery of the drugs from a polymeric drug delivery device can be fabricated from either a non degradable polymer, such as ethylene-vinyl acetate copolymer, a bio erodible polymer such as poly[bis(p-carboxyphenoxy)alkane anhydride]. 28
  29. 29. Sonophoresis-activated drug delivery systems 29
  30. 30. 7. Iontophoresis-activated drug delivery systems uses electrical current to activate and to modulate the diffusion of a charged drug molecule across the skin in a facilitated rate 30
  31. 31.  skin permeation rate of a charged molecule i consist of 3 components Jiisp = Jp+Je+Jc Jp = passive skin permeation flux Je = electrical current driven permeation flux Jc = convection flow-driven skin permeation flux IONSYS - fentanyl iontophoretic transdermal system Example : development of an iontophoretic DDS of dexamethasone sodium phosphate 31
  32. 32. 8. Hydration-activated drug delivery system Depends on the hydration induced swelling process to activate the release of drug Drug reservoir is homogeneously dispersed in a swellable polymer matrix fabricated from a hydrophilic polymer Release of the drug is controlled by the rate of swelling of the polymer matrix. Example is VALRELEASE tablet- diazepam in hydrocolloid and pharmaceutical excipients. In stomach absorbs the gastric fluid & forms colloidal gel that starts from the tablet surface and grows inward. 32
  33. 33.  release of the drug is controlled by matrix diffusion through this gel barrier 33
  34. 34. REFERENCES NOVEL DRUG DELIVERY SYSTEMS, 2nd edition,Yie W. Chien CONTROLLED DRUG DELIVERY- FUNDAMENTALS AND APPLICATIONS, 2nd edition, edited by Joseph R. Robinson and Vincent H. L. Lee http://www.rxlist.com/ionsys-drug.htm 34
  35. 35. THANK YOU 35

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