Microspheres as drug delivery system


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Microspheres as drug delivery system

  2. 2.  Microspheres can be defined as solid, approximately spherical particles ranging in size from 1 to 1000 μm. Made up of polymeric, waxy, or other protective materials such as starches, gums, proteins, fats, and waxes and used as drug carrier matrices for drug delivery. Microcapsules: micrometric reservoir systems Microspheres: micrometric matrix systems. Natural polymer can also be used: Albumin Gelatin 2
  3. 3. = Polymer Matrix Drug Core Polymer Coat } = Entrapped Drug MICROCAPSULES MICROSPHERES•Microspheres are essentially spherical in shape, whereas, microcapsules may be spherical or non-spherical in shape.•Microparticles, either microcapsules or microspheres, as the same: ‘microcapsules’. 3
  4. 4.  Alternative Terms used in place of microspheres:  Microbeads  Beads 4
  5. 5.  They facilitate accurate delivery of small quantities of potent drug and reduced concentration of drug at site other than the target organ or tissue. They provide protection for unstable drug before and after administration, prior to their availability at the site of action. They provide the ability to manipulate the in vivo action of the drug, pharmacokinetic profile, tissue distribution and cellular interaction of the drug. They enable controlled release of drug. • Ex: narcotic, antagonist, steroid hormones 5
  6. 6.  Microcapsule: consisting of an encapsulated core particle. Entrapped substance completely surrounded by a distinct capsule wall. Types of Microspheres Microcapsule Micromatrix Micro-matrix: Consisting of homogenous dispersion of active ingredient in particle. 6
  7. 7. Biodegradable Non-biodegradable• Lactides & • Poly methyl Glycolides and methacrylate their copolymers • Acrolein• Polyanhydrides • Epoxy Polymer• Polycynoacrylates • Glycidyl methacrylate 7
  8. 8. 8
  9. 9.  Longer duration of action  Control of content release Increase of therapeutic efficacy  Protection of drug  Reduction of toxicity  Biocompatibility  Sterilizability  Relative stability Water solubility or dispersibility  Bioresorbability  Targetability 9  Polyvalent
  10. 10. • Taste and odour masking• Conversion of oil and other liquids, facilitating ease of handling• Protection of the drug from the environment• Delay of volatilisation 10
  11. 11. • Freedom from incompatibilities between drug and excipients, especially the buffers• Improvement of flow properties• Dispersion of water insoluble substance in aqueous media• Production of sustained release, controlled release and targeted medication 11
  12. 12.  Solvent evaporation method  Single emulsion technique  Double emulsion technique Coacervation phase separation method Spray drying and spray congealing method 12 Polymerization method
  13. 13. A. Single Emulsion Technique Aq solution /suspension of stirring / polymer(natural sonication polymer)Heat denaturation (byadding dispersionTo heated oil) linking cross Dispersion in Organic phase oil/CHCl3Chemical crosslinking(butanol,HCHO,Glutaraldehyde) 14
  14. 14. Microspheres in Microspheres in org.phase org.phase Centrifugation, washing, & separation Microspheres 14
  15. 15. B. Double Emulsion Technique Aqueous solution of polymerdispersion in oil/orgenic phase, vigorous homogenisation(sonication) Primary emulsion(w/o)addition of aqueous solution of PVA W/O/W multiple emulsion Addition of large aqu. phase Microspheres in solution 16
  16. 16. Separation, washing, drying MICROSPHERES 16
  17. 17. C)PolymerizationA)Normal Polymerization Normal Polymerization is done by bulk, suspension, precipitation, emulsion and polymerization process.1. Bulk polymerization: Heated to Monomer initiate + polymerizatio Bioactive n Polymer Moulded/fra Microsphere material Initiator (block) gmented s + accelerate rate of Initiator reaction 17
  18. 18. B)Suspension polymerization Monomer Bioactive material Initiator Dispersion in water and stebilizer DropletVigorous Aggitation Polymerization by Heat Hardened microspheres Separation & Drying MICROSP HERES 18
  19. 19. c)Emulsion Polymerization Monomer/ Aq.Solution of NaOH,Bioactive material Initiator, Surfactant , Stabilizer Dispersion with vigorous stirring Micellar sol. Of Polymer in aqueous medium Polymarization Microspheres formation MICROSPHERES 19
  20. 20. D)Phase Separation Coacervation Aq./organic solution of polymerDrug dispersed or dissolved in the polymer solution Phase sepration by salt addition, non solvent addition add. Incompatible polymer,etc Polymer rich globules Hardening Microspheres in aqu./organic phase separation/drying MICROSPHERES 20
  21. 21. E)Spray Drying Polymer dissolve in volatile organic solvent(acetone,dichloromethane) Drug dispersed in polymer solution under high speed homogenization Atomized in a stream of hot air Due to solvent evaporation small droplet or fine mist form Leads to formation of MicrospheresMicrospheres separated from hot air by cyclone separator, Trace of solvent are removed by vacuum drying 21
  22. 22. F)Solvent Extraction Drug is dispersed in organic solvent (water miscible organic solvent such as Isopropanol) Polymer in organic solvent Organic phase is removed by extraction with water(This process decreasing hardening time for microspheres) Hardened microspheres 22
  23. 23. G)Precipitation Method An emulsion is formed, which consists of polar droplets dispersed in a non-polar medium. Solvent may be removed from the droplets by the used of a co-solvent. The resulting increase in the polymer-drug concentration causes a precipitation forming a suspension of microspheres. 23
  24. 24. Oral deliveryParenteral delivery 24
  25. 25. 1. Degradation controlled monolithic system.2. Diffusion controlled monolithic system.3. Diffusion controlled reservoir system.4. Erodible poly agent system. 25
  26. 26.  Electron Microscopy, Scanning Electron Microscopy and Scanning Tunneling Microscopy – Surface Characterization of Microspheres Fourier Transform Raman Spectroscopy or X-ray Photoelectron Spectroscopy –to Determine If Any Contaminants Are Present Surface Charge Analysis Using Micro-electropshoresis –Interaction of Microspheres Within the Body 26
  27. 27. 27
  28. 28. The most widely used procedures to visualize micro particles are conventional lightmicroscopy (LM) and scanning electron microscopy (SEM). 28
  29. 29. LM provides a control over coating parameters in case of double walled microspheres. The microspheres structures can be visualized before and after coating and the change can be measured microscopically.SEM allows investigations of the microspheres surfaces and after particles are cross-sectioned, it can also be used for the investigation of double walled systems.Conflocal fluorescence microscopy is used for the structure characterization of multiple walled microspheres.Laser light scattering and multi size coulter counter other than instrumental methods, which can be used for the characterization of size, shape and morphology of the microspheres. 29
  30. 30. 30
  31. 31.  It is done by using rotating paddle apparatus and Dialysis method Determine wetting properties of Microparticulate carriers 31
  32. 32. The surface chemistry of the microspheres can be determined using the electronspectroscopy for chemical analysis (ESCA). ESCA provides a means for thedetermination of the atomic composition of the surface. The spectra obtainedusing ECSA can be used to determine the surfacial degradation of thebiodegradable microspheres. 32
  33. 33.  Used to determine the degradation of the polymeric matrix of the carrier system. Surface of microspheres are investigated by ATR. ATR-FT-IR provides surface composition of microspheres. IR beam is Reflected passed IR spectra many times through the of surface through the ATR cell material sample 33
  34. 34.  Can be determined by using MULTI VOLUME PYCHNOMETER 2 readings Helium is are noted From 2 Placed in introduced Expansion of reading Weigh Multi in the results in reduction volume assample in volume chamber decrease in pressure well as a cup pychnomet and in pressure at different density is er allowed to initial determined expand pressure 34
  35. 35.  The micro electrophoresis is an apparatus used to measure the electrophoretic mobility of microspheres from which the isoelectric point can be determined. Mean velocity at different Ph values ranging from 3-10 is calculated by measuring the time of particle movement over a distance of 1 mm. using this data the electrical mobility of the particle can be determined. The electrophoretic mobility can be related to surface contained charge, ionisable behaviour or ion absorption nature of the microspheres. 35
  36. 36.  Measured by using RADIOACTIVE GLYCINE C14 glycine ethyl ester hydrochloride Radioactive EDAC glycine conjugate Microspheres 36
  37. 37.  RADIOACTIVITY is then measured by using LIQUID SCINTILLATION COUNTER Carboxylic acid residue can be find out 37
  38. 38. Beaker Method• Dosages form is adhere to the bottom of the beaker containing medium.• Overhead stirrer is used.• Volume of medium-50-500ml• Speed 60-300rpm 38
  39. 39. A. Oral Before use, the aqueous phase D. Protein cavity and 1-octanol were saturated with binding containingcontaining 1- drug in buffer each other. octanol C. Body B. Buccal Samples were withdrawn and fluids membrane returned to compartment A with a containing containing 1- syringe. 0.2M HCl octanol 39
  40. 40.  Consist of KC-Cell containing distilled water (50ml) at 370C as dissolution medium TMDDS was placed in a glass tube fitted with a 10# sieve at the bottom which reciprocate in the medium at 30 strokes per min. 40
  41. 41.  Animal used: dog, rabbits, rat, cat, hamster, pigs, and sheep RAT: The oesophagus is ligated to prevent absorption pathways other than oral mucosa At different time intervals, the blood is withdrawn and analysed 41
  42. 42. Percent of Drug Dissolved Vs Dissolution Rate Vs Absorption% of drug dissolved In-vitro Vs Percent of Drug Rate Peak plasma concentration Absorbed It is expected that a poorly If the dissolution rate is the limiting In the analysis of in vitro and in formulated dosage form step in the absorption of the drug, vivo drug correlation, rapid releases amount of drug than and is absorbed completely after drug absorption may be from a well formulated dosage dissolution, a linear correlation may distinguished from the slower form, and, hence the amount of be obtained by comparing the drug absorption by observation percent of the drug absorbed to the drug available for absorption is percent of the drug dissolved. If the of the absorption time for the less for poorly formulated rate limiting step in the dosage form. The quicker the dosage form than from a well bioavailability of the drug is the absorption of the drug the less formulated dosage form. rate of absorption of the drug, a is the absorption time required change in the dissolution rate may for the absorption of the certain not be reflected in a change in the amount of the drug. The time rate and the extent of drug required for the absorption of absorption from the dosage form the same amount of drug from the dosage form is correlated
  43. 43.  MICROSPHERES IN VACCINE DELIVERY. Eg ; Diphtheria toxoid , Tetanus toxoid. TARGETED DRUG DELIVERY. Eg ; ocular, eye (cornea).etc CONTROLLED RELEASE. Eg ; GI tumors, Bone tumors. CHEMOEMBOLIZATION. IMMUNO MICROSPHERES 43
  44. 44. 44