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Implantable Drug Delivery System

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various approaches to design implantable drug delivery system.

various approaches to design implantable drug delivery system.

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  • 1. Approaches to the development of Implantable drug delivery system(Parenteral drug delivery system)
    Prepared by:
    Paresh K Bharodiya
    09PCT07
    Guided by:
    Dr. Ajay B. Solanki
    Department of pharmaceutics
    A.R College & G.H Patel Institute of Pharmacy
    12/05/2010
  • 2. List of contents
    Effect of physicochemical properties on parenteral absorption
    Introduction
    Approaches to design implantable drug delivery systems
    (a) Controlled drug delivery by diffusion process
    Polymer membrane permeation- controlled drug delivery
    Matrix diffusion-controlled drug delivery
    Microreservior partition-controlled drug delivery system
    Membrane matrix hybrid-type drug delivery system
    (b) Controlled drug delivery by activation process
    Osmotic pressure
    Vapor pressure
    Magnetically
    Hydration
    Hydrolysis
    (c) Controlled drug delivery by feed back regulated mechanism
    Bioerosion
    Bioresponce
    REFRENCES
  • 3. Effect of Physicochemical Properties on Parenteral Absorption
    Drug particle in suspension
    Drug solutes in solution
    Dissolution
    Partitioning
    Absorption
    Systematic circulation
    Drug solution in tissue fluid
    Target tissue
    Elimination
  • 4. Rate of dissolution of solid in formulation vehicle
    Particle size and crystal habit
    pH of the formulation
    pKa of drug
    Lipophillicity of the drug
    Tissue fluid/vehicle partition coefficient
    Solubility of drug at biological fluid at injection site
    Presence of other ingredients in the formulation and their interaction with the drug molecule
  • 5. Implantable drug delivery systeman introduction
    Implantable drug delivery systems are placed completely under the skin — usually in a convenient but inconspicuous location. The patient is aware of only a small bump under the skin.
    designed to transmit drugs and fluids into the bloodstream without the repeated insertion of needles.
    well suited to the drug delivery requirements of insulin, steroids, chemotherapeutics, antibiotics, analgesics, total parenteral nutrition, and heparin
    There is little chance of infection or interference with daily activities Because the device is completely subcutaneous, with no opening in the skin
  • 6. Approaches to the development of Implantable drug delivery system
    In 1861 Lafarge pioneered the concept of IDDS for long term continuous administration of crystalline hormone in the form of solid steroid pellet
    But the release profile was not constant and can not be readily controlled in terms of precision of the release rate and duration of action
    While it is possible to surgically implant and remove drug-concentrative devices or polymeric matrices, the requirement for such intervention could have a significant negative impact on the acceptability
    Two approaches to this problem seem possible
    Use of implanted electrically driven pumps
    Use of erodible implants
  • 7. Number of approaches have been developed to achive controlled administration of drugs via implantation
    (1) Controlled drug delivery by diffusion process
    Diffusion of the drug out of the device or solvent into the polymer ultimately contributes to the drug-release process
    Release of the drug from the device is preprogrammed at a specific rate profile
    This is accomplished by a system design which controls molecular diffusion of drug in or and/or across barrier medium surrounding the system
    This systems can be further sub classified in to number of classes
  • 8. (A)Polymer membrane permeation- controlled drug delivery using
    Non porous membrane
    Micro porous membrane
    Semi permeable membrane
    Here the drug formulation is totally or partially encapsulated within a drug reservoir compartment and the drug release surface is covered by a rate limiting polymeric membrane having a specific permeability for drug
    drug reservoir
    polymeric membrane
    Drug contained in a formulation
  • 9.
    • The dug reservoir can exist in to a solid , suspension or in a solution form and polymeric membrane fabricated in the form of non porous{homogenous or heterogeneous}, micro porous or semipermiable membrane.
    • 10. Encapsulation of drug formulation in to the reservoir compartment can be done by
    Injection molding
    Spray coating
    microencapsulation
    Different shapes of the systems like sphere , cylinder or sheet can be fabricated
    • An example of this type of implantable drug delivery system is A NORPLANT SUBDERMAL IMPLANT and OCUSERT SYSTEM
  • (b) Polymer Matrix diffusion-controlled drug delivery
    In this type of preplanned drug delivery system the drug reservoir is prepared by homogenous dispersion of drug particles in a rate controlling polymer matrix fabricated from either a lipophillic or a hydrophilic polymer
    The drug dispersion in a polymer matrix is done by
    Blending finely divided drug particles with a liquid polymer or a viscous base followed by cross linking of the polymer chain
    Mixing the drug with a polymer at an elevated temperature
    Dissolving drug and polymer in a common solvent followe by solvent evaporation at elevated temperature or under vacuum
    The resultant drug polymer dispersion is then molded or extruded to form a drug delivery devices of various shapes
    Example is a nitro-dur TDDS
  • 11. Drug reservoir{dispersion}
    Drug release
    Gel layer
    Drug depleted zone
    Drug release
    Hydrophilic polymer
    Swollable matrix
    Lipophillic polymer
    Non swollable matrix
  • 12. (C) Microreservior partition-controlled drug delivery system
    In this type drug reservoir is fabricated by micro dispersion of aqueous suspension of a drug using a high energy dispersion technique in to a biocompatible polymer such as silicone elastomer to form a homogenous dispersion of many discrete , unreachable microscopic drug reservoir
    Depending on the physicochemical properties of the drug and the desired rate of drug release , the device can be further coated with polymer to modify mechanism and rate of release
    example is the transdermal nitro disc system
  • 13. Polymer matrix
    Microscopic Drug reservoir
    {liquid compartment}
    Coating membrane
    Polymer -solution interface
  • 14. (d) Membrane matrix hybrid-type drug delivery system
    This device is a hybrid of Polymer Matrix diffusion-controlled drug delivery and Polymer membrane permeation- controlled drug delivery system aim is to take advantage of controlled release kinetic offered by Polymer membrane permeation- controlled drug delivery system and to avoid risk of dose dumping from reservoir compartment of this type of drug delivery system
    Drug reservoir is formed by dispersion of drug in to a polymer matrix which is further coated by a semi permeable polymeric membrane
    Example is a norplant II sub dermal system
  • 15. (II) Controlled drug delivery by activation process
    In this type release of the drug is activated by some physical , chemical, or biological process and/or by the energy supplied externally and the rate of release is than regulated by the processes applied or input of energy
    Based on the processed applied these activation modulated drug delivery system can be classified in to
    Osmotic pressure activated
    Vapor pressure activated
    Magnetically activated
    Hydrolytic-activated
    Hydration activated
  • 16. Osmotic pressure activated drug delivery system
    In this type of controlled drug delivery system the release of the drug takes place due to osmotic pressure
    Drug reservoir which can be either a solid or a suspension is contained in a semipermiable housing
    The release is activated through a specially formed orifice and rate of release is modulated by controlling the osmotic gradient
    Thus release rate is dependent on water permeability of membrane, solubility of osmogen, effective surface area of semipermiable housing as well as osmotic gradient
    Representatative example of this type of implantable controlled release drug delivery system is alzet osmotic pump
  • 17. Alzet osmotic pump
  • 18. Vapor pressure activated implantable drug delivery system
    The drug reservoir which ids a solution formulation is contained in to an infusate chamber
    By freely movable bellow the chamber is a pumping system physically separated from the vapors pressure chamber which contains vaporizable fluids such as a fluorocarbon
    The fluorocarbon vaporizes at body temperature creating a vapor pressure that pushes bellow to move upward and forces the drug solution to get delivered
  • 19. Magnetically activated implantable drug delivery system
    • A magnetic wave triggered mechanism is incorporated in to drug delivery device and drug can be triggered to be released at varying rate depending on the magnitude and duration of the electromagnetic energy applied
    Magnetic ring
    Coated polymer
    Magnet inside polymer matrix
  • 20. Hydration activated drug delivery system
    This system depends on the hydration induced swelling process by tissue fluid at implantable site to activate drug release
    In this system drug reservoir is dispersed in to swollable polymer matrix fabricated from hydrophilic polymer that become swollen upon hydration
    Drug is released from microscopic water filled pore channels in to the polymer matrix and
    Release rate of drug is controlled by swelling of the polymer matrix
  • 21. Hydrolysis activated drug delivery system
    Release of drug is activated by hydrolysis of a bioerodable polymer by the cell fluid at the implantation site
    Biodegradable polymer like
    Co(lactic-glycolic)polymer
    Poly(orthoester)
    Poly(anhydride) are used in fabrication of this type of implantable drug delivery system
    This system is made by dispersing loading dose of a drug with a biodegradable polymer , which is then molded in to pellet or a bead shaped implant
    Example is a LHRH{goserelin} releasing biodegradable sub dermal implant
  • 22. (c) Controlled drug delivery by feed back regulated mechanism
    using this group of controlled drug delivery system the release of a drug is activated by some biochemical molecule in the body and its concentration at the implantable site via feedback mechanism
    And the rate of controlled release of drug is regulated by the concentration of biochemical substance detected by a sensor in the feedback mechanism
  • 23. Bioerosion regulated drug delivery system
    This system consist of a drug dispersed in to a biodegradable polymer matrix like poly vinyl methyl ether and is coated with immobilized urease in a neutral pH.in the presence of urea urease at the surface of drug delivery system metabolize urea to form ammonia causing increase in pH at which polymer degrades leading to drug release
    Hydrocortisone release
    Urease
    U
    U
    U
    U
    U
    U
    U
    U
    U
    U
    U
    U
    U
    U
    U
    Erosion
    Ammonia
    Urea
    Hydrocortisone
    Alkaline pH
    Polymer
  • 24. Bioresponce activated drug delivery system
    Drug reservoir is contained in a device enclosed by a bioresponsive polymer membrane whose permeability is controlled by conc. of a biochemical agent contained where the system is located
    Example is a glucose triggered insulin delivery system in which insulin reservoir is capsulated within hydrogel membrane having amineNR2 groups
    In alkaline pH NR2 is neutral and membrane is unsellable and impermeable to insulin
    As glucose, triggering agent penetrates in to membrane it is oxidized to glucuronic acid by enzyme glucose oxidise contained in a membrane
    NR2 groups are protonated and hydro gel membrane becomes swollable and permeable for insulin.
    Amt of release is dependant on the concentration of glucose entering in to membrane
  • 25. REFRENCES
    NOVEL DRUG DELIVERY SYSTEM, Yie. W Chien, second edition, marceldekker inc, page 381
    DRUG DELIVERY SYSTEMS, Vasant V. RanadeMannfred A. Hollinger Second Edition,