Rate Controlled Drug Delivery System


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Rate Controlled Drug Delivery System

  1. 1. CONCEPT AND SYSTEM DESIGN OF RATE- CONTROLLED DRUG DELIVERY SYSTEM -: Presented By :- Amruta S. Sambarekar 1st Year M.Pharm Dept. of Pharmaceutics M M C P, BELGAUM
  2. 2. CONTENTS Introduction Rate Pre-programmed Drug Delivery System Activation Modulated Drug Delivery System Feedback regulated Drug Delivery System Effect of System Parameters on Controlled Drug Delivery System References February 11, 2013 2
  3. 3. INTRODUCTIONSustained release, sustained action, controlled release,extended action, timed release dosage forms are the termsused to identify drug delivery systems that are designed toachieve a prolonged therapeutic effect by continuouslyreleasing medication over an extended period of time afterthe administration of single dose.The term “Controlled release” has become associated withthose systems from which therapeutic agents may beautomatically delivered at predefined rates over a longperiod of time.But, there are some confusion in terminology between“Controlled release” & “Sustained release” February 11, 2013 3
  4. 4. Sustained Release : The term sustained release has been constantly used to describe a pharmaceutical dosage form formulated to retard the release of a therapeutic agent such that its appearance in the systemic circulation is delayed &/or prolonged & its plasma profile is sustained in duration. Controlled Release : This term on the other hand, has a meaning that goes beyond the scope of sustained drug action. It also implies a predictability & reproducibility in the drug release kinetics, which means that the release of drug ingredient from a controlled delivery system proceeds at a rate profile that is not only predictable kinetically, but also reproducible from one unit to another. February 11, 2013 4
  5. 5. An ideal controlled drug delivery system is the one which delivers the drug at a predetermined rate, locally or systematically for aspecified period of time. February 11, 2013 5
  6. 6. Advantages :1. Less fluctuation in drug blood levels.2. Reduction in dosing frequency.3. Improved patient convenience & compliance.4. Avoidance of night time dosing.5. More uniform efffect.6. Reduction in GI irritation and dose related side effects Disadvantages :1. Decreased systemic availability in comparison to immediate release conventional dosage forms.2. Poor in vivo – in vitro correlation.3. Possibility of dose dumping.4. Retrieval of drug is difficult. February 11, 2013 6
  7. 7. CLASSIFICATIONBased on their technical sophistication : Rate preprogrammed drug delivery system Activation-modulated drug delivery system Feedback-regulated drug delivery system Site targeting drug delivery system February 11, 2013 7
  8. 8. RATE PREPROGRAMMED DRUG DELIVERY SYSTEMIn this group , the release of drug molecule from thesystem has been preprogrammed at specific rate profile.They can be classified asPolymer membrane permeation-controlled drug delivery systemPolymer matrix diffusion-controlled drug delivery systemMicroreservior partition-controlled drug deliverysystem February 11, 2013 8
  9. 9. 1.POLYMER MEMBRANE PERMEATION- CONTROLLED DRUG DELIVERY SYSTEMIn this type, drug is totally or partially encapsulated within drugreservoir.Its drug release surface is covered by a rate-controlling polymericmembrane having a specific permeability.Drug reservoir may exist in solid, suspension or solution form. Polymeric membrane may be nonporous or microporous i.esemipermeable membrane.Encapsulation of the drug formulation inside the Polymer membranereservoir compartment is accomplished byinjection,spray-coating,capsulation Drug reservoiror micro-encapsulation. Drug release February 11, 2013 9 9
  10. 10. The rate of drug release is defined by, Q = Km/r Ka/m DdDm x CR t Km/r Dmhd + Ka/m DdhmWhere, Km/r & Ka/m = partition coefficient of the drug molecule from reservoir to rate controlling membrane & from membrane to aq. Layer respectively. Dm & Dd = diffusion coefficient of rate controlling membrane & aqueous diffusion layer respectively. hm & hd = thickness of rate controlling membrane & aqueous diffusion layer respectively. CR – drug conc. In reservoir compartment. February 11, 2013 10
  11. 11. Release of drug molecules is controlled by : Partition coefficient of the drug molecule. Diffusivity of the drug molecule. The thickness of the rate controlling membrane. February 11, 2013 11
  12. 12. Ex. Progestasert IUD The drug reservoir is a suspension of progesterone & barium sulphate in silicone medical fluid & is encapsulated in the vertical limb of a T- shaped device walled by a non-porous membrane of ethylene-vinyl acetate co- polymer. It is designed to deliver natural progesterone continuously in uterine cavity at a daily dosage rate of at least 65 μg/day to achieve contraception for 1 year. February 11, 2013 12
  13. 13. Ex.Ocusert February 11, 2013 13
  14. 14. In the Ocusert system the drug reservoir is a thindisk of Pilocarpine alginate complex sandwitchedbetween two transparent sheets of etylene vinylacetate copolymer membrane. Microporous membrane permit the tear fluid topenetrate into the drug reservoir compartment todisssolve pilocarpine from the complexPilocarpine molecules are then released at a constantrate of either 20or 40 µg/hr for the management ofglaucoma for upto 7 days February 11, 2013 14
  15. 15. Ex.Transderm- nitro D Adhesive layer Drug resevoir , a dispersion of nitroglycerine-lactose triturate in thesilicon medical fluid, is encapsulated in thin ellipsoidal patch. It is constructed from a drug impermeable metallic plastic laminate as thebacking membrane and a constant surface of rate controllingmicrosporous membrane of etylene- vinyl acetate copolymer as the drugreleasing surface Deliver nitroglycerine at dosage rate of 0.50 mg/cm²/day for transdermalabsorption to provide daily relief of Angina attacks. February 11, 2013 15
  16. 16. 2.POLYMER MATRIX DIFFUSION-CONTROLLED DRUG DELIVERY SYSTEM In this type, drug reservoir is prepared by homogeneously dispersing drug particle in rate controlling polymer matrix from either a lipophilic or a hydrophilic polymer. The drug dispersion in the polymer matrix is accomplished by either,1. blending therapeutic dose of drug with polymer or highly viscous base polymer, followed by cross linking of polymer chains.2. mixing drug solid with rubbery polymer at elevated temp. Polymer membrane Drug depletion Drug dispersed in polymer matrix zone drug release 16 16 drug release
  17. 17. The rate of the drug release from this system, Q = (2ACRDp)1/2t½ Where, Q/t1/2 - rate of release of drug A – initial drug loading dose in the polymer matrix CR – drug solubility in polymer Dp – diffusivity of drug in polymer matrix February 11, 2013 17
  18. 18. Release of drug molecule is controlled by Loading dose Polymer solubility of drug Drug diffusivity in polymer matrix.Ex. Nitro-Dur : Nitro-Dur is a transdermal system contains nitroglycerin in acrylic-based polymer adhesives with a resinous cross-linking agent to provide a continuous source of active ingredient. February 11, 2013 18
  19. 19. It is designed for application on to intact skin for 24 hrs toprovide a continuous transdermal infusion of nitroglycerinat dosage rate of 0.5 mg/cm2/day for the treatment ofangina pectoris. 19
  20. 20. February 11, 2013 3.MICRORESERVIOR PARTITION- CONTROLLED DRUG DELIVERY SYSTEMIn this type, drug reservoir is fabricated by micro dispersion ofan aqueous Suspension of drug in biocompatible polymer suchas silicon elastomers to form homogeneous dispersion using ahigh energy dispersion technique.Depending upon the physicochemical properties of drugs &desired rate of drug release, the device can be further coatedwith a layer of biocompatible polymer to modify themechanism & the rate of drug release.Polymer membrane Microdispersion of drug in biocompatable polymer February 11, 2013 20 20drug release.
  21. 21. The rate of drug release is defined by, ] (dQ = DpDdmKp dt Dphd + DdhpmKp hl [ nSp – DlSl(1-n) 1+1 kl KmWhere, n = the ratio of drug conc. at the inner edge of the interfacial barrier over the drug solubility in the polymer matrix. m = a/b, a – ratio of drug conc. In the bulk of elution solution over drug solubility in the same medium. b – ratio of drug conc. at the outer edge of the polymer coating membrane over drug solubility in the same polymer. February 11, 2013 21
  22. 22. Kl, Km & Kp = partition coefficient for the interfacial partitioning of the drug from the liquid compartment to the polymer matrix, from the polymer matrix to the polymer-coating membrane & from the polymer coating membrane to the elution solution respectively.Dl, Dp & Dd = diffusivities of the drug in the lipid layer surrounding the drug particle, the polymer coating membrane enveloping the polymer matrix, & the hydrodynamic diffusion layer surrounding the polymer coating membrane with the thickness hl, hp & hd.Sl & Sp = solubilities of the drug in the liquid compartments & in the polymer matrix, respectively. February 11, 2013 22
  23. 23. Release of drug molecules from this type of systemcan follow either a dissolution or a matrix diffusioncontrolled process depending upon the relativemagnitude of Sl & Sp.Release of drug molecule is controlled by,Partition coefficientDiffusivity of drugSolubility of drug February 11, 2013 23
  24. 24. Ex. Syncro mate - c It is fabricated by dispersing the drug reservoir, which is a suspension of norgestomet in an aqueous solution of PEG 400, in a viscous mixture of silicone elastomer. February 11, 2013 24
  25. 25. After adding the catalyst, the suspension will bedelivered into the silicone medical grade tubing,which serves as mold as well as the coatingmembrane & then polymerized in situ.The polymerized drug polymer composition is thencut into a cylindrical drug delivery device with theopen ends.It is designed to be inserted into the subcutaneoustissue of the livestock’s ear flap & to releasenorgestomet for up to 20 days for control of estrus& ovulation as well as for up to 160 days for growthpromotion. February 11, 2013 25
  26. 26. Ex.Transdermal Nitro discDrug reservoir is formed by a suspension of nitroglycerine and lactosetriturate in aqueous solution of 40% polyethylene glycol 400 and dispersing it with isopropyl palmitate as dispersing agent , in a mixture of viscous siliconeelastomer.Drug polymer dispersion is then molded to form a solid medicated disk insitu on a drug –impermeable metallic plastic laminate, with surrroundingadhesive rim, by injections molding under instantaneous heating.Transdermal administration of nitroglycerine at a daily dosage of 0.5 mg/cm²for once aday medication of angina pectoris February 11, 2013 26
  27. 27. References Novel drug delivery system- Y.W.Chien. Pg no. 1-132 Biopharmaceutics & pharmacokinetics- Brahmankar. Pg no. 335 - 370 Fundamentals of controlled release drug delivery- Robinson. Pg no. 482 - 508 Web – www.google.comFebruary 11, 2013 February 11, 2013 27 27
  28. 28. February 11, 2013 28