0
 Approaches to the development of Implantable drug delivery system(Parenteral drug delivery system)<br />Prepared by: <br ...
List of contents	<br />Effect of physicochemical properties on parenteral absorption<br />Introduction<br />Approaches to ...
Effect of Physicochemical Properties on Parenteral Absorption<br />Drug particle in suspension<br />Drug solutes in soluti...
Rate of dissolution of solid in formulation vehicle<br />Particle size and crystal habit<br />pH of the formulation<br />p...
Implantable drug delivery systeman introduction <br />Implantable drug delivery systems are placed completely under the sk...
Approaches to the development of Implantable drug delivery system<br />In 1861 Lafarge pioneered the concept of IDDS for l...
Number of approaches have been developed to achive controlled administration of drugs via implantation<br />(1)  Controlle...
(A)Polymer membrane permeation- controlled drug delivery using<br />Non porous membrane<br />Micro porous membrane<br />Se...
<ul><li>The dug reservoir can exist in to a solid , suspension or in a solution form and polymeric membrane fabricated in ...
Encapsulation of drug formulation in to the reservoir compartment can be done by</li></ul>Injection molding<br />Spray coa...
Drug reservoir{dispersion}<br />Drug release<br />Gel layer<br />Drug depleted zone <br />Drug release<br />Hydrophilic po...
(C) Microreservior partition-controlled drug delivery system<br />In this type drug reservoir is fabricated by micro dispe...
Polymer matrix<br />Microscopic  Drug reservoir<br />{liquid compartment}<br />Coating membrane<br />Polymer -solution int...
(d) Membrane matrix hybrid-type drug delivery system<br />This device is a hybrid of Polymer Matrix diffusion-controlled d...
(II) Controlled drug delivery by activation process<br />In this type release of the drug is activated by some physical , ...
Osmotic pressure activated drug  delivery system <br />In this type of controlled drug delivery system the release of the ...
Alzet osmotic pump<br />
Vapor pressure activated implantable drug  delivery system <br />The drug reservoir which ids a solution formulation is co...
Magnetically activated implantable drug  delivery system <br /><ul><li>A magnetic wave triggered mechanism is incorporated...
Hydration activated drug delivery system <br />This system depends on the hydration induced swelling process by tissue flu...
Hydrolysis activated drug delivery system <br />Release of drug is activated by hydrolysis of a bioerodable polymer by the...
(c) Controlled drug delivery by feed back regulated mechanism<br />using this group of controlled drug delivery system the...
Bioerosion regulated drug delivery system <br />This system consist of a drug dispersed in to a biodegradable polymer matr...
Bioresponce activated drug delivery system <br />Drug reservoir is contained in a device enclosed by a bioresponsive polym...
REFRENCES<br />NOVEL DRUG DELIVERY SYSTEM, Yie. W Chien, second edition, marceldekker inc, page 381<br />DRUG DELIVERY SYS...
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Implantable Drug Delivery System

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various approaches to design implantable drug delivery system.

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  1. 1. Approaches to the development of Implantable drug delivery system(Parenteral drug delivery system)<br />Prepared by: <br />Paresh K Bharodiya<br />09PCT07<br />Guided by: <br />Dr. Ajay B. Solanki<br />Department of pharmaceutics<br />A.R College & G.H Patel Institute of Pharmacy<br />12/05/2010<br />
  2. 2. List of contents <br />Effect of physicochemical properties on parenteral absorption<br />Introduction<br />Approaches to design implantable drug delivery systems<br />(a) Controlled drug delivery by diffusion process<br />Polymer membrane permeation- controlled drug delivery<br />Matrix diffusion-controlled drug delivery<br />Microreservior partition-controlled drug delivery system<br />Membrane matrix hybrid-type drug delivery system<br />(b) Controlled drug delivery by activation process<br />Osmotic pressure<br />Vapor pressure<br />Magnetically<br />Hydration<br />Hydrolysis<br />(c) Controlled drug delivery by feed back regulated mechanism<br />Bioerosion<br />Bioresponce<br />REFRENCES<br />
  3. 3. Effect of Physicochemical Properties on Parenteral Absorption<br />Drug particle in suspension<br />Drug solutes in solution<br />Dissolution <br />Partitioning <br />Absorption <br />Systematic circulation<br />Drug solution in tissue fluid<br />Target tissue<br />Elimination <br />
  4. 4. Rate of dissolution of solid in formulation vehicle<br />Particle size and crystal habit<br />pH of the formulation<br />pKa of drug<br />Lipophillicity of the drug<br />Tissue fluid/vehicle partition coefficient<br />Solubility of drug at biological fluid at injection site<br />Presence of other ingredients in the formulation and their interaction with the drug molecule<br />
  5. 5. Implantable drug delivery systeman introduction <br />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.<br />designed to transmit drugs and fluids into the bloodstream without the repeated insertion of needles.<br />well suited to the drug delivery requirements of insulin, steroids, chemotherapeutics, antibiotics, analgesics, total parenteral nutrition, and heparin<br />There is little chance of infection or interference with daily activities Because the device is completely subcutaneous, with no opening in the skin<br />
  6. 6. Approaches to the development of Implantable drug delivery system<br />In 1861 Lafarge pioneered the concept of IDDS for long term continuous administration of crystalline hormone in the form of solid steroid pellet<br />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 <br />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<br />Two approaches to this problem seem possible<br />Use of implanted electrically driven pumps<br />Use of erodible implants<br />
  7. 7. Number of approaches have been developed to achive controlled administration of drugs via implantation<br />(1) Controlled drug delivery by diffusion process<br />Diffusion of the drug out of the device or solvent into the polymer ultimately contributes to the drug-release process<br />Release of the drug from the device is preprogrammed at a specific rate profile<br />This is accomplished by a system design which controls molecular diffusion of drug in or and/or across barrier medium surrounding the system<br />This systems can be further sub classified in to number of classes <br />
  8. 8. (A)Polymer membrane permeation- controlled drug delivery using<br />Non porous membrane<br />Micro porous membrane<br />Semi permeable membrane<br />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<br />drug reservoir<br />polymeric membrane<br />Drug contained in a formulation<br />
  9. 9. <ul><li>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. 10. Encapsulation of drug formulation in to the reservoir compartment can be done by</li></ul>Injection molding<br />Spray coating <br />microencapsulation <br />Different shapes of the systems like sphere , cylinder or sheet can be fabricated<br /><ul><li>An example of this type of implantable drug delivery system is A NORPLANT SUBDERMAL IMPLANT and OCUSERT SYSTEM</li></li></ul><li>(b) Polymer Matrix diffusion-controlled drug delivery<br />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<br />The drug dispersion in a polymer matrix is done by <br />Blending finely divided drug particles with a liquid polymer or a viscous base followed by cross linking of the polymer chain<br />Mixing the drug with a polymer at an elevated temperature <br />Dissolving drug and polymer in a common solvent followe by solvent evaporation at elevated temperature or under vacuum<br />The resultant drug polymer dispersion is then molded or extruded to form a drug delivery devices of various shapes<br />Example is a nitro-dur TDDS<br />
  11. 11. Drug reservoir{dispersion}<br />Drug release<br />Gel layer<br />Drug depleted zone <br />Drug release<br />Hydrophilic polymer<br />Swollable matrix<br />Lipophillic polymer <br />Non swollable matrix <br />
  12. 12. (C) Microreservior partition-controlled drug delivery system<br />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<br />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 <br /> example is the transdermal nitro disc system<br />
  13. 13. Polymer matrix<br />Microscopic Drug reservoir<br />{liquid compartment}<br />Coating membrane<br />Polymer -solution interface<br />
  14. 14. (d) Membrane matrix hybrid-type drug delivery system<br />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 <br />Drug reservoir is formed by dispersion of drug in to a polymer matrix which is further coated by a semi permeable polymeric membrane <br />Example is a norplant II sub dermal system <br />
  15. 15. (II) Controlled drug delivery by activation process<br />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<br />Based on the processed applied these activation modulated drug delivery system can be classified in to <br />Osmotic pressure activated<br />Vapor pressure activated<br />Magnetically activated<br />Hydrolytic-activated<br />Hydration activated<br />
  16. 16. Osmotic pressure activated drug delivery system <br />In this type of controlled drug delivery system the release of the drug takes place due to osmotic pressure <br />Drug reservoir which can be either a solid or a suspension is contained in a semipermiable housing <br />The release is activated through a specially formed orifice and rate of release is modulated by controlling the osmotic gradient<br />Thus release rate is dependent on water permeability of membrane, solubility of osmogen, effective surface area of semipermiable housing as well as osmotic gradient<br /> Representatative example of this type of implantable controlled release drug delivery system is alzet osmotic pump<br />
  17. 17. Alzet osmotic pump<br />
  18. 18. Vapor pressure activated implantable drug delivery system <br />The drug reservoir which ids a solution formulation is contained in to an infusate chamber<br />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 <br />The fluorocarbon vaporizes at body temperature creating a vapor pressure that pushes bellow to move upward and forces the drug solution to get delivered <br />
  19. 19. Magnetically activated implantable drug delivery system <br /><ul><li>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</li></ul>Magnetic ring<br />Coated polymer <br />Magnet inside polymer matrix<br />
  20. 20. Hydration activated drug delivery system <br />This system depends on the hydration induced swelling process by tissue fluid at implantable site to activate drug release <br />In this system drug reservoir is dispersed in to swollable polymer matrix fabricated from hydrophilic polymer that become swollen upon hydration <br />Drug is released from microscopic water filled pore channels in to the polymer matrix and <br />Release rate of drug is controlled by swelling of the polymer matrix <br />
  21. 21. Hydrolysis activated drug delivery system <br />Release of drug is activated by hydrolysis of a bioerodable polymer by the cell fluid at the implantation site<br />Biodegradable polymer like<br />Co(lactic-glycolic)polymer <br />Poly(orthoester)<br />Poly(anhydride) are used in fabrication of this type of implantable drug delivery system <br />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<br />Example is a LHRH{goserelin} releasing biodegradable sub dermal implant<br />
  22. 22. (c) Controlled drug delivery by feed back regulated mechanism<br />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<br />And the rate of controlled release of drug is regulated by the concentration of biochemical substance detected by a sensor in the feedback mechanism<br />
  23. 23. Bioerosion regulated drug delivery system <br />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<br />Hydrocortisone release <br />Urease <br />U<br />U<br />U<br />U<br />U<br />U<br />U<br />U<br />U<br />U<br />U<br />U<br />U<br />U<br />U<br />Erosion <br />Ammonia <br />Urea <br />Hydrocortisone <br />Alkaline pH<br />Polymer <br />
  24. 24. Bioresponce activated drug delivery system <br />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<br />Example is a glucose triggered insulin delivery system in which insulin reservoir is capsulated within hydrogel membrane having amineNR2 groups <br />In alkaline pH NR2 is neutral and membrane is unsellable and impermeable to insulin <br />As glucose, triggering agent penetrates in to membrane it is oxidized to glucuronic acid by enzyme glucose oxidise contained in a membrane <br />NR2 groups are protonated and hydro gel membrane becomes swollable and permeable for insulin.<br />Amt of release is dependant on the concentration of glucose entering in to membrane<br />
  25. 25. REFRENCES<br />NOVEL DRUG DELIVERY SYSTEM, Yie. W Chien, second edition, marceldekker inc, page 381<br />DRUG DELIVERY SYSTEMS, Vasant V. RanadeMannfred A. Hollinger Second Edition, <br />
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