controlled drug delivery system classification

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controlled drug delivery system classification

  1. 1. Controlled Drug Delivery System Classification
  2. 2. Activation-modulated Drug Delivery System <ul><li>In this group of controlled release drug delivery system, the release of drug molecules from the delivery system is activated by some physical, chemical, or biochemical process and/or by energy supplied externally. </li></ul><ul><li>The rate of drug release is then controlled by regulating the process applied or energy input. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  3. 3. Classification : By Physical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS Osmotic pressure Activated
  4. 4. Osmotic Pressure Activated DDS 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Drug reservoir ( API + osmotic agent) Delivery Orifice Semi-permeable Membrane. (cellulose esters)
  5. 5. <ul><li>For the drug delivery system containing a solution formulation, the intrinsic rate of drug release is defined by, </li></ul><ul><li>Q Pw Am </li></ul><ul><li>t hm </li></ul><ul><li>For the drug delivery system containing a solid formulation, the intrinsic rate of drug release is defined by, </li></ul><ul><li>Q Pw Am </li></ul><ul><li>t hm </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. ( π s – π e ) = ( π s – π e ) Sd =
  6. 6. <ul><li>Where, </li></ul><ul><li>Q/t - rate of drug release </li></ul><ul><li>P w - permiability of semipermiable housing </li></ul><ul><li>A m -effective S.A. of semipermiable housing </li></ul><ul><li>h m - thickness of semipermiable housing </li></ul><ul><li>( π s - π e ) – Differential osmotic pressure b/w </li></ul><ul><li>DDS with osmotic pressure p s & </li></ul><ul><li>environmental osmotic pressure p e </li></ul><ul><li>Sd – Aqueous solubility of drug contained in the </li></ul><ul><li>solid formulation. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  7. 7. <ul><li>Release is controlled at rate determined by, </li></ul><ul><li>Water permeability </li></ul><ul><li>Surface area of semi-permeable housing </li></ul><ul><li>Osmotic pressure gradient </li></ul><ul><li>Merits : </li></ul><ul><li>A high degree of in vivo- in vitro correlation (IVIVC) is obtained in osmotic systems. </li></ul><ul><li>For oral osmotic systems, drug release is independent of gastric pH and hydrodynamic conditions. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  8. 8. 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Alzet Osmotic Pump
  9. 9. Classification : By Physical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS Osmotic pressure Activated Hydrodynamic Press. Activated
  10. 10. Hydrodynamic Pressure - Activated DDS 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  11. 11. <ul><li>Rate of drug release is defined by, </li></ul><ul><li>Where, </li></ul><ul><li> P f = fluid permeability </li></ul><ul><li> A m = effective Surface area </li></ul><ul><li> h m = thickness of wall with anular opening </li></ul><ul><li>(  s -  e ) = differential hydrodynamic pressure </li></ul><ul><li>between DDS and environment. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Q Pf Am t hm = (  s -  e )
  12. 12. <ul><li>Release is controlled at rate determined by, </li></ul><ul><li>Fluid permeability </li></ul><ul><li>Pressure gradient </li></ul><ul><li>Surface area of wall with annular opening </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  13. 13. Classification : By Physical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS Osmotic pressure Activated Hydrodynamic Press. Activated Vapor Pressure Activated
  14. 14. Vapor Pressure – Activated DDS 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  15. 15. <ul><li>The rate of drug release is defined by, </li></ul><ul><li> Q = d 4 (P s -P e ) </li></ul><ul><li>t 40.74 ml </li></ul><ul><li>Where- </li></ul><ul><li>Q/t - rate of drug release </li></ul><ul><li>d - Inner diameter of cannula </li></ul><ul><li>l - length of cannula </li></ul><ul><li>(P s -P e ) - the difference between the vapor pressure in the vapor chamber & pressure at the implantation site. </li></ul><ul><li>m - viscosity of the drug solution. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  16. 16. <ul><li>Rate controlled By : </li></ul><ul><li>Differential vapor pressure </li></ul><ul><li>Formulation viscosity </li></ul><ul><li>Size of the delivery cannula </li></ul><ul><li>Example, </li></ul><ul><li>An implantable infusion pump for constant </li></ul><ul><li>infusion of heparin in anticoagulant treatment, morphine for patients suffering from the intense pain of terminal cancer. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  17. 17. Classification : By Physical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS Osmotic pressure Activated Hydrodynamic Press. Activated Vapor Pressure Activated Mechanically Activated
  18. 18. Mechanically – Activated DDS <ul><li>In this type, drug reservoir is in solution form retained in a container equipped with mechanically activated pumping system. </li></ul><ul><li>A measured dose of the drug formulation is reproducible delivered in to a body cavity, for ex. The nose, through the spray head upon manual activation of the drug delivery pumping system. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  19. 19. <ul><li>Ex. Metered-dose Inhaler </li></ul><ul><li>the volume of solution delivered is controllable, as small as 10-100 μ l & is independent of the force & duration of the activation applied as well as the solution volume in the container. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  20. 20. Classification : By Physical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS Osmotic pressure Activated Hydrodynamic Press. Activated Vapor Pressure Activated Mechanically Activated Magnetically Activated
  21. 21. Magnetically Activated - DDS 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  22. 22. <ul><li>In this type, drug reservoir is a dispersion of peptide or protein powders in polymer matrix from which macromolecular drug can be delivered only at a relatively slow rate. </li></ul><ul><li>Device is fabricated by positioning a tiny magnet ring in core of hemispherical drug dispersing polymer matrix. </li></ul><ul><li>The external surface is coated with drug impermeable polymer (ethylene vinyl acetate or silicone elastomer) except one cavity at the centre of the flat surface. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  23. 23. <ul><li>e.g. This delivery device used to deliver protein drugs such as bovine serum albumin, at a low basal rate, by a simple diffusion process under non triggering condition. </li></ul><ul><li>As the magnet is activated to vibrate by an external electromagnetic field, the drug molecules are delivered at a much higher rate. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  24. 24. Classification : By Physical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS Osmotic pressure Activated Hydrodynamic Press. Activated Vapor Pressure Activated Mechanically Activated Magnetically Activated Sonophoresis Activated
  25. 25. Sonophoresis - Activated DDS <ul><li>This type of system utilizes ultrasonic energy to activate or trigger the delivery of drug from polymeric drug delivery device. </li></ul><ul><li>System can be fabricated from nondegradable polymer (ethylene vinyl acetate) or bioerodiable polymer (poly[bis(p-carboxyphenoxy) alkane anhydride]. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  26. 26. 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  27. 27. Classification : By Physical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS Osmotic pressure Activated Hydrodynamic Press. Activated Vapor Pressure Activated Mechanically Activated Magnetically Activated Sonophoresis Activated Ionto- phoresis Activated
  28. 28. Iontophoresis - Activated DDS <ul><li>Iontophorsis can be defined as the process in which the flux or rate of absorption of ionic solutes into or through skin is enhanced by applying a voltage drop/electrical field across the skin. </li></ul><ul><li>In addition, delivery rate can be controlled by the intensity of applied electric current or Electro-chemical potential gradient. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  29. 29. <ul><li>Iontophoresis – facilitated skin permeation rate of charged molecule (i) consist of 3 components & is expressed by, </li></ul><ul><li>J i isp = J p + J e +J c </li></ul><ul><li>J p – passive skin permeation flux. </li></ul><ul><li>J e – electrical current driven permeation flux </li></ul><ul><li>J c = convective flow driven skin permeation flux </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  30. 30. 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  31. 31. Merits : <ul><li>Non-invasive technique as a substitute for chemical enhancers. </li></ul><ul><li>Frequency of dosage is reduced. </li></ul><ul><li>Provide predictable and extended duration of action. </li></ul><ul><li>Demerits : </li></ul><ul><li>Excessive current density leads to pain. </li></ul><ul><li>The safe current density varies with electrode size. </li></ul><ul><li>Mol. Wt. of 8000-12000 results in a uncertain rate of delivery. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  32. 32. Classification : By Physical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS Osmotic pressure Activated Hydrodynamic Press. Activated Vapor Pressure Activated Mechanically Activated Magnetically Activated Sonophoresis Activated Ionto- phoresis Activated Hydration Activated
  33. 33. Hydration - Activated DDS 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Valrelease Tablets
  34. 34. <ul><li>Not only hydrophilic polymer but also the lipophilic polymers, such as silicone elastomer, can be modified to have swelling properties. </li></ul><ul><li>This is achieved by impregnating water-miscible liquid such as glycerol and/or water soluble salt such as, sodium chloride, in lipophilic polymer matrix. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  35. 35. Classification By : Chemical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS pH-Activated DDS
  36. 36. pH-Activated DDS <ul><li>This type of chemically activated system permits targeting the delivery of drug only in the region with selected pH range. </li></ul><ul><li>It fabricated by coating the drug-containing core with a pH – sensitive polymer combination. </li></ul><ul><li>For instances, a gastric fluid labile drug is protected by encapsulating it inside a polymer membrane that resist the degradative action of gastric pH, such as combination of ethyl-cellulose and hydroxymethylcellulose phthalate. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  37. 37. 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  38. 38. Classification By : Chemical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS pH-Activated DDS Ion-Activated DDS
  39. 39. Ion-Activated DDS 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  40. 40. <ul><li>An ionic or a charged drug can be delivered by this method & this system are prepared by first complexing an ionic drug with an ion-exchange resin containing a suitable counter ion. </li></ul><ul><li>Ex. By forming a complex between a cationic drug with a resin having a So 3 - group or between an anionic drug with a resin having a N(CH 3 ) 3 group. </li></ul><ul><li>The granules of drug-resin complex are first treated with an impregnating agent & then coated with a water-insoluble but water-permeable polymeric membrane. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  41. 41. <ul><li>This membrane serves as a rate-controlling barrier to modulate the influx of ions as well as the release of drug from the system . </li></ul><ul><li>Limitations : </li></ul><ul><li>The rate of release of the drug is directly proportional to the concentration of ions at the site of action. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  42. 42. Classification By : Chemical Means 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. Activation- Modulated DDS pH-Activated DDS Ion-Activated DDS Hydrolysis-Activated DDS
  43. 43. Hydrolysis-Activated DDS <ul><li>This type of system depends upon hydrolysis process to activate the release of drug. </li></ul><ul><li>Drug reservoir is either encapsulated in microcapsules or homogeneously dispersed in microspheres or nano particles for injection . </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  44. 44. <ul><li>It can also be fabricated as an implantable device. </li></ul><ul><li>All these systems prepared from bioerodible or biodegradable polymers (polyanhydride, o-ester). </li></ul><ul><li>It is activated by hydrolysis-induced degradation of polymer chain & is controlled by rate of polymer degradation. </li></ul><ul><li>Ex. LHRH – releasing biodegradable subdermal implant, which is designed to deliver goserline, a synthetic LHRH analog for once a month treatment of prostate carcinoma. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  45. 45. Classification By : Biochemical Means <ul><li>Enzyme - Activated Drug Delivery System </li></ul><ul><li>This type of biochemical system depends on the enzymatic process to activate the release of drug. </li></ul><ul><li>Drug reservoir is either physically entrapped in microspheres or chemically bound to polymer chains from biopolymers (albumins or polypeptides). </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  46. 46. <ul><li>The release of drug is activated by enzymatic hydrolysis of biopolymers (albumins or polypeptides) by specific enzyme in target tissue. </li></ul><ul><li>Ex. Albumin microspheres release 5 – fluorouracil in a controlled manner by protease – activated biodegradation. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  47. 47. Feedback Regulated Drug Delivery System <ul><li>In this group the release of drug molecules from the delivery system is activated by a triggering agent. </li></ul><ul><li>Rate of drug release is controlled by concen. of triggering agent. </li></ul><ul><li>They are further classified as </li></ul><ul><li>Bioerosion -regulated drug delivery system </li></ul><ul><li>Bioresponsive drug delivery system </li></ul><ul><li>Self-regulating drug delivery system </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  48. 48. A. Bioerosion - Regulated DDS 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  49. 49. .Bioresponsive DDS <ul><li>in this type, the drug reservoir is contained in a device enclosed by bio-responsive membrane whose drug permeability is controlled by conce. of biochemical agent. </li></ul><ul><li>e.g . glucose-triggered insulin drug delivery system. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  50. 50. 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  51. 51. C. Self-Regulating DDS <ul><li>This type of system depends on a reversible & competitive binding mechanism to activate and to regulate the release of drug. </li></ul><ul><li>Drug reservoir is drug complex encapsulated within a semi permeable polymeric membrane. </li></ul><ul><li>The release of drug from the delivery system is activated by the membrane permeation of biochemical agent from the tissue in which the system is located </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  52. 52. 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  53. 53. Effect Of System Parameters On CDDS 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. <ul><li>Polymer & Solution Solubility </li></ul><ul><li>Polymer & Solution Diffusivity </li></ul><ul><li>Thickness of polymer diffusion path & hydro- </li></ul><ul><li>dynamic layer </li></ul><ul><li>Partition Co-efficient </li></ul><ul><li>Surface Area </li></ul><ul><li>Loading Dose </li></ul>
  54. 54. Polymer Solubility <ul><li>For drug to be release, the drug molecules on the outmost surface must dissociate from its crystal lattice structure, partition or dissolve in surrounding medium. </li></ul><ul><li>As the solubility of drug particles in rate controlling membrane and polymer matrix plays rate-controlling role in release from a polymeric device. To release at an appropriate rate the drug should have adequate polymer solubility. </li></ul><ul><li>Rate of drug release is directly proportional to magnitude of polymer solubility. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  55. 55. Solution Solubility <ul><li>Aqueous solubility varies from one drug to another. </li></ul><ul><li>Difference in aqueous solubility is depend on the difference in their chemical structure, types & physicochemical nature of functional groups & the variations in their stereo chemical configurations . </li></ul><ul><li>Drug release increases with increase in Solution solubility of drug. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  56. 56. Partition Coefficient <ul><li>Partition co-efficient K of a drug for it ’ s interfacial partitioning from the surface of a drug delivery device towards an elution medium as given : </li></ul><ul><li>K = C s /C p </li></ul><ul><li>Where, </li></ul><ul><li>C s = conc. Of drug at the solution/polymer interface </li></ul><ul><li>C p = solubility of drug in the polymer phase. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  57. 57. <ul><li>Any variation in either C s or C p result in increase or decrease in magnitude of ‘ K ’ value. </li></ul><ul><li>Rate of drug release increase with increase in partition coefficient </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  58. 58. Polymer Diffusivity <ul><li>The diffusion of small molecules in a polymer structure is a energy activated process in which the diffusant molecules move to a successive series of equilibrium positions when a sufficient amount of energy of activation for diffusion E d , has been acquired by the diffusant & it ’ s surrounding polymer matrix. </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  59. 59. <ul><li>Magnitude of polymer diffusivity is dependant upon type of functional group and type of stereo chemical position in diffusant molecule. </li></ul><ul><li>The bulkier the functional group attached to polymer chain lower the polymer diffusivity. </li></ul><ul><li>Polymer diffusivity also depends on , </li></ul><ul><li>1) Effect of cross linking (inverse relationship) </li></ul><ul><li>2) Effect of crystallinity (inverse relationship) </li></ul><ul><li>3) Effect of fillers </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  60. 60. Solution Diffusivity <ul><li>The diffusion of solute molecules in solution medium is a result of the random motion of molecules. </li></ul><ul><li>Under concentration gradient molecule diffuse spontaneously from higher concentration to lower concentration. </li></ul><ul><li>Diffusivity of solute molecule in aqueous solution usually decreases as its concentration increases </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  61. 61. 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. <ul><li>Thickness of hydro- dynamic diffusion layer </li></ul><ul><li>Surface Area </li></ul><ul><li>Loading Dose. </li></ul>
  62. 62. Reference <ul><li>Novel Drug Delivery System- Y.W.Chien. </li></ul><ul><li>published by Marcel Dekkar, inc., New York </li></ul><ul><li>Pg no. 17-36 & 57-111 </li></ul><ul><li>Controlled And Novel Drug Delivery – N.K.Jain CBS Publishers & Distributors, New Delhi. </li></ul><ul><li>www.pharmainfo.net </li></ul>22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P.
  63. 63. 22/01/2011 B R Nahata College of Pharmacy ,Mandsaur M.P. ?

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