Parenteral controlled release drug delivery system -by varsha phirke

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Parenteral Controlled release drug delivery system- approaches, mechanism-Dissolution controlled depot formulation, Adsorption type depot formulation, Encapsulation type depot formulation, Esterification type depot formulation, In situ forming drug delivery systems (ISFD)-Thermoplastic pastes, In situ cross linked systems, In situ polymer precipitation, Thermally induced gelling system, In situ solidifying organogels, examples; Long acting contraceptives: Injectables -Depo-Provera C-150 (Depot Medroxyprogesterone acetate injection), Deladroxate, Norethindrone releasing biodegradable polymer based suspension, Norethindrone enanthate in oleaginous solutions, Norgestrel 17 beta fatty acid esters; Sub dermal- Hormonal intrauterine device (Mirena - also known as IUC or IUS), Nonhormonal intrauterine device with copper (US -Paragard), Subdermal contraceptive implant (US - Nexplanon/ Implanon/ Implanon NXT); internationally– Norplant- Jadelle; Implants: mechanism-Controlled drug release by diffusion(Membrane permeation-controlled release system, Matrix diffusion-controlled release system, Micro-reservoir dissolution-controlled release system, Membrane matrix hybrid type-controlled release system), Controlled drug release by activation (Osmotic pressure activated eg.- Alzet pump, Vapour pressure activated eg.- Infusaid pump, Magnetically activated, Phonophoresis, Hydrolysis activated eg.- for control release of levonorgestrel (poly ortho esters used) Hydration activated eg.- Hydron implant; Controlled drug delivery by feedback regulated: mechanism-Bioerosion regulated drug delivery system, Bioresponse activated drug delivery system; examples; case study- atrigel, References

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Parenteral controlled release drug delivery system -by varsha phirke

  1. 1. Parenteral Controlled Release SystemSeminar By: Varsha PhirkeM Pharm (Pharmaceutics)Guided by: Mrs. Pallavi ChaudhariPadm. Dr. D. Y. Patil College of Pharmacy, Akurdi1
  2. 2. Contents: Terminology Approaches Mechanism Injectable drug delivery system Long acting contraceptive formulations Implantable drug delivery Quality Control Case study References2
  3. 3. TerminologyParenteral is the introduction of nutrition, a medication, orother substance into the body via a route other than the mouth,especially via infusion, injection or implantation.Controlled Release drug delivery systems aim to maintainplasma concentration of drugs within the therapeutic windowfor a longer period of time3
  4. 4. Difference between IR-SR-CR in terms of plasma concentration4
  5. 5. Approaches:1) Use of viscous, water miscible vehicles, such as an aqueoussolution of gelatin or polyvinyl pyrrolidone.Change in solubility characteristics of drugChange in time of release once drug is administeredChange in state of drug post administration2) Utilization of water immiscible vehicles, such as vegetableoil, some water repelling agents, like aluminium monostearate.3) Formation of thixotropic suspensionStructural break pointChange in flow propertiesChange in dissolution characteristics5
  6. 6. Approaches:4) Preparation of water insoluble drug derivatives such as salts,complexes and esters.Chemical modification without affecting therapeutic activityKinetics are influencedStability is enhanced5) Dispersion in polymeric microspheres, or microcapsules such aslactides-glycolides homopolymers or copolymersUse of Surface active agentPolymerization insitu or through reactionMicrocapsules using various techniques6) Co-administration of vasoconstrictors6
  7. 7. Mechanism:On the basis of different mechanism, depot formulation categoriesinto four types1) Dissolution controlled depot formulation2) Adsorption type depot formulation3) Encapsulation type depot formulation4) Esterification type depot formulation7
  8. 8. Class Mechanism Rate limiting step ExamplesDissolutioncontrolleddepotDrug absorption iscontrolled by slowdissolution of drugparticle.Dissolution of drugparticles.Formation of salt orcomplexes with lowaqueous solubility,Suspension ofMacrocrystals.Adsorptiontype depotBinding of drugmolecules toadsorbent [Al(OH)3]Rate ofabsorption.Vaccine preparationsEncapsulationtype depotEncapsulating drugwithin permeationbarrier /dispersingdrug particles in adiffusion matrix.Permeation acrossthe permeationbarrier & the rateof biodegradation.Naltrexone pamoate-releasing biodegradablemicrocapsule, liposome, &Norethindrone-releasingbiodegradable beads.Esterificationtype depotEsterifying drug toform bioconvertibleProdrug-type ester& then intoinjection.Number ofenzyme present,Interfacialpartitioning ofdrug esters.Fluphenazine enanthate,nandrolone decanoate inoleaginous solution.8
  9. 9. Injectable drug delivery systemIn situ forming drug delivery systems (ISFD)Classified into five categories according to their mechanism of depotformation:Thermoplastic pastesIn situ cross linked systemsIn situ polymer precipitationThermally induced gelling systemIn situ solidifying organogels.MicrospheresLiposomesSuspensionSolid lipid nanoparticles9
  10. 10. Class Mechanism of depot formation ExamplesThermoplasticpastesSemisolid polymers which injected as amelt and form a depot upon cooling tobody temperature.D,L-lactide, glycolide,E-caprolactone, dioxanone andorthoestersIn situ crosslinked polymersystemsCross-linked polymer network can befound in situ by free radical reactionsinitiated by heat (thermosets) /absorptionof photon / ionic interactions betweensmall cation & polymer anions.Benzoyl peroPEG(polyethyleneglycol)-oligo-glycol-acrylate, using aphoto initiator, suchas eosinxide( banned)In situ polymerprecipitationWater-insoluble and biodegradablepolymer in biocompatible organic solvent.Phase separation and precipitation of thepolymer forming the depot at the site ofinjectionAtrigelThermallyinduced gellingsystemGelation at body temperature when highlyconcentrated polymer solution>15% w/w were injectedPEO-PPO-PEO(pluronics or poloxamers)In situsolidifyingorganogelsWater insoluble amphiphilic lipids, whichswell in water and forms various types oflyotropic liquid crystals.Glycerol monooleate/monopalmitostearate/monolinoleate, sorbitanmonostearate (SMS) & differentgelation modifiers (polysorbates 2010
  11. 11. Generic name Trade name Dosage formPenicillin & Procaine Duracillin Squibb Suspension injectionMedroxyprogesteroneacetateDepo-Provera, Upjohn Suspension injectionFluphenazine enanthate anddecanoateProlixin enanthate andProlixin decanoate; Squibboil solutionsMicrocrystallinedeoxycorticosone pivalatePercortan pivalate; Ciba oleaginous suspensionNandrolone decanoate Decadurabolin, Organon injectionInsulin Zinc Utralente, Lente andsemilente, NovosuspensionsTestosterone enanthate /estradiol valerate in ethyloleate BDitate - DS, Savage repository vehicle11
  12. 12. Long acting contraceptives formulations:(A)Injectables:Depo-Provera C-150 (Depot Medroxyprogesterone acetate injection)DeladroxateNorethindrone releasing biodegradable polymer basedsuspensionNorethindrone enanthate in oleaginous solutionsNorgestrel 17 beta fatty acid esters(B)IUD’s and subdermal implants:Hormonal intrauterine device (Mirena - also known as IUC or IUS)Nonhormonal intrauterine device with copper (US -Paragard)Subdermal contraceptive implant (US - Nexplanon/ Implanon/Implanon NXT); internationally– Norplant- Jadelle12
  13. 13. Implants13
  14. 14. Approaches:A Controlled drug release by diffusion1) Membrane permeation-controlled release systemNon porous membranes,Porous membranesSemiporous membraneseg. - Norplant subdermal implants of levonorgestrel2) Matrix diffusion-controlled release systemLipophilic polymersHydrophilic polymersPorous polymerseg. - Compudose implant of estradiol3) Micro-reservoir dissolution-controlled release systemHydrophilic reservoir in lipophilic matrixLipophilic reservoir in hydrophilic matrixeg. - Synchro-mate implant of norgestomet4) Membrane matrix hybrid type-controlled release systemLipophilic membrane with hydrophilic matrixHydrophilic membrane with lipophilic matrixeg.- Norplant II subdermal implant of Levonorgesterl (4 years) 14
  15. 15. Approaches:B Controlled drug release by activationOsmotic pressure activated eg.- Alzet pumpVapour pressure activated eg.- Infusaid pumpMagnetically activatedPhonophoresisHydrolysis activated eg.- for control release of levonorgestrel(poly ortho esters used)Hydration activated eg.- Hydron implantC Controlled drug delivery by feedback regulatedmechanismBioerosion regulated drug delivery systemBioresponse activated drug delivery system15
  16. 16. Approach Mechanism exampleMembrane permeation-controlled releaseDrug encapsulated incapsule / sphericalcompartmentNorplant subdermalimplantMatrix diffusion-controlledreleaseHomogenous dispersion ofdrug in lipophilic/hydrophilic polymer matrixCompudose implantMicro-reservoir dissolution-controlled releaseDrug in suspension inaqueous solution of watermiscible polymer formsdispersion of drug reservoirin polymer matrixSyncro mate implantMembrane matrix hybridtype-controlled releaseHybrid of polymermembrane permeationcontrolled DDS andPolymer matrix diffusioncontrolled DDSNorplant IIA. Controlled drug release by diffusion16
  17. 17. Approach Mechanism ExamplesOsmotic pressure activated Drug reservoir solution orsemisolid placed withinsemipermeable housing withcontrolled water permeabilityAlzet osmotic pumpVapour pressure activated Drug reservoir is solution isplaced inside infusate chamberInfusaid pumpMagnetically activated Magnetic wave triggeringmechanism is incorporatedinto drug delivery deviceHydrolysis activated Solid drug is homogenouslydispersed throughout polymermatrix of bioerodible orbiodegradable polymerLevonorgestrel using Polyortho estersbiodegradable polymerHydration activated Solid drug is coated byhydrophilic polymerHydron implantB. Controlled drug release by activation17
  18. 18. C. Controlled drug delivery by feedback regulated mechanismApproach MechanismBioerosion regulated Drug dispersed bioerodible matrix fabricatedwith polymer coated with immobilised ureaseBioresponse activated Drug enclosed in bioresponsive polymerwhose permeability is controlled byconcentration of biochemical agent in tissue18
  19. 19. Quality Control of Parenterals1) Sterility Tests.2) Pyrogen Tests.3) Leaker Tests.4) Particulate matter testing.5) Weight variation or content uniformity6) Bacterial endotoxin test19
  20. 20. 20Case studyPatel D. B. et al in Journal of Global Pharma Technology, 2010; 2(2):85-90 has presented an article on Atrigel® system describing it as aproven sustained-release drug delivery platform that delivers therapeuticlevels of a wide spectrum of drugs over a few days to several months with asingle injection. Atrigel system is used for both Parenterals and site-specific drug delivery. The ease of manufacture of the Atrigel system andits relatively pain-free subcutaneous injection into the body providesignificant advantages over both solid implants and micro particles. Mostof the standard biodegradable polymers can be used in the Atrigeltechnology. The hydrophilic solvents employed in the Atrigel system todissolve the polymers. The low- molecular- weight polymers at lowpolymer concentrations can be easily injected into the body using standardneedles. The high molecular- weight polymers at high polymerconcentrations may be used as gels or putties that can be placed into sitesin the body where they solidify and provide support. Atrigel technologyprovides a more stable, ready-to-use formulation.
  21. 21. References:Yie W. Chien, Marcel Dekker Inc.; Novel Drug Delivery Systems- New York, Volume50, 381:517J. R. Robinson, V. H. Lee; Controlled drug delivery- fundamentals and applications-Marcel Dekker Inc., volume-20, 2nd edition, 5:58, 179:208, 484:515K. E. Avis, H. A. Lieberman, L. Lachman; Pharmaceutical Dosage forms: Parenteralmedications- Marcel Dekker Inc., Volume 1, 2nd edition, 1:-55, 5:106Xiaoling Li, Bhaskara Jasti; Design of Controlled Release Drug delivery systems-McGraw-Hill Publications, 107:124, 139:168, 203:229Vasant Ranade, Mannfred Hollinger; Drug delivery systems-CBS Publications, SecondEdition, 115:135G. S. Banker, C. T. Rhodes; Modern Pharmaceutics- Marcel Dekker Inc., 4th edition,381:414, 501:52821
  22. 22. References:N. K. Jain; Advances in Controlled and novel drug delivery-CBS Publications, 1stedition 2010, 204:229Vyas S. P., Khar R. K. In; Controlled Drug Delivery Concepts and Advances- CBSPublication, 1st edition 2002, 452:457Vyas S. P., Khar R. K. In; Targeted and Controlled Drug Delivery- CBS Publication,4th edition, 2005, 213:215Michael J. Akers, D. S. Larrimore, D. M. Guazzo; Parenteral Quality Control-CBSPublications, 2008, 3:17, 124:183, 287:354Hitesh Bari; A prolonged release Parenterals drug delivery system – an overview,International Journal of Pharmaceutical Sciences Review and Research, Volume 3,Issue 1, July – August 2010; Article 001Patel D. B. et al., Journal of Global Pharma Technology. 2010; 2(2): 85-9022

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