-:CONTENTS OF SEMINAR :Introduction Advantage Polymar used for preparation General Method of Preparation Characterization of Microspheres. Application of Microspheres

-: INTRODUCTION :´

Microspheres are solid , approximately spherical particles ranging 1-1000µm in size.

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They are made up of polymeric substance in which the drug is dispersed through out the microspheres matrix.

ADVANTAGE OF MICROSPHERES:  They facilitate accurate delivery of small quantities of potent drug and reduced concentration of drug at site other than the target organ or tissue. Ex: narcotic. prior to their availability at the site of action. pharmacokinetic profile.  They provide the ability to manipulate the in vivo action of the drug. tissue distribution and cellular interaction of the drug. steroid hormones .  They provide protection for unstable drug before and after administration.  They enable controlled release of drug. antagonist.

POLYMER USED FOR MICROSPHERES PREPARATION: Biodegradable Polyme: Lactides&Glycolides and their copolymer NON Biodegradable Polyme: Poly methyl methacrylate Acrolein Polyanhydrides Epoxy Polymer Polycynoacrylates Glycidyl methacrylate .

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especially the buffers ´ ´ ´ Improvement of flow properties Safe handling of test masking Dispersion of water insoluble substance in aqueous media . facilitating ease of handling Protaction of the drug from the environment Delay of volatillisation Freedom from incompatibilities between drug and excipients.THE ADMINISTRATION PARAMETERS THAT CAN BE SATISFACTORILY CONTROLLED ARE AS FOLLOW: ´ ´ ´ ´ ´ Taste and odour masking Conversion of oil and other liquids.

GENERAL METHOD OF PREPARATION: a) Single Emulsion Technique b) Double Emulsion Technique c) Polymerization Technique d) Phase Separation Coacervation e) Spray drying &spray coating f) Solvent Extraction .

A) SINGLE EMULSION TECHNIQUE Aqous solution /suspension of polymer(natural polymer) stirring / sonication dispersion in orgenic phase oil/chcl3 cross linking Heat denaturation (by adding dispersion To heated oil) chemical crosslinking (butanol.Glutaraldehyde) .HCHO.

MICROSPHERES IN ORG.SEPARATION MICROSPHERES .PHASE MICROSPHERES IN CENTRIFUGATION.WASHING.PHASE ORG.

vigorous homogenisation(sonication) Primary emulsion(w/o) addition of aqueous solution of PVA W/O/W multipal emulsion addition of large aq.B) DOUBLE EMULSION TECHNIQUE Aqueous solution of polymer dispersion in oil/orgenic phase. Phase MICROSPHERES in solution .

DRYING MICROSPHERES .WASHING.SEPARATION.

1. pption. Bulk polymerization: Monomer Bioactive material Initiator Heated to initiate polymerization Initiator accelerate rate of raction Polymer(Block) Moulded/fragmented MICROSPHERES . suspension.emulsion and polymerization process.C)POLYMERIZATION A)Normal Polymerization:  Normal Polymerization is done by bulk.

Aggitation Polymerization by Heat Hardened microspheres Separation&Drying MICROSP HERES .B)SUSPENSION POLYMERIZATION Monomer Bioactive material Initiator Dispersion in water and stebilizer Droplet Vigorous .

Solution of NaOH. Stabilizer Dispersion with vigorous stirring Micellar sol.3) EMULSION POLYMERISATION Monomer/ Bioactive material Aq. Of Polymer in aqueous medium Polymarization Microspheres formation MICROSPHERES . Surfactant . Initiator.

D)PHASE SEPRATION COACERVATION Aq.etc Polymer rich globules Hardening microspheres in aqu./orgenic phase sepration/drying MICROSPHERES ./orgenic solution of polymer Drug dispersed or dissolved in the polymer solution Phase sepration by salt addition. Incompatible polymer. non solvent addition add.

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 Microspheres Microspheres separated from hot air by cyclone separator.Trace of solvent are removed by vacuum drying .

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 .

CHARACTERIZATION PROPERTIES OF MICROSPHERES 1] Particle size analysis 2] Scanning electron microscopy (SEM) study 3] Flow properties 4] Thermal analysis 5] Determination of percentage yield 6] Drug content 7] Determination of drug loading 19 .

8] Incorporation efficiency of microspheres 9] Determination of solubility 10] Dissolution studies of microspheres 20 .

pure samples. A microscopical field was scanned by video camera. spays dried microspheres were determined by microscopic method using calibrated ocular micrometer. The morphology and particle sizes were determined in a Digital microscope equipped with a 1/3´CCD camera imaging accessory The microspheres were dispersed on a microscope slide.1] PARTICLE SIZE ANALYSIS Particle size of recrystallized sample. 21 . The images of the scanned field are analyzed by the softwar. A microscopical image analysis technique for determination of particle size was applied.

which was placed latter gold sputtering in san SEM chamber. A small amount of powder was spread on an aluminum stub. Obtained photograph to identify and confirm spherical nature and Surface topography of the crystals. 22 . Photographs were taken at an acceleration voltages of 20 KV electron beam.] SCANNING ELECTRON MICROSCOPY (SEM) STUDY The morphology of microspheres was examined by scanning election microscopy.

The microspheres were carefully poured through the funnel until the apex of the conical pile so formed just reached the tip of the funnel. above graph paper placed on a flat horizontal surface.3] FLOW PROPERTIES Flow properties of the microspheres were evaluated by determining the angle of repose and the compressibility index. a) The angle of repose of microsphere and commercial crystals was measured by fixed funnel method. A funnel with the end of the stem cut perpendicular to the axis of symmetry is secured with its tip at a given height (1 cm). Static angle of repose was measured according to the fixed funnel and free standing cone method of Banker and Anderson. 23 . H.

Thus. the R being the radius of the base of the microspheres conical pile: . tan = H/ R or = tan-1 (H/ R) where = the angle of repose 24 .

25 .(V/V0)] x 100 Apparent particle densities of microsphere were measured using a Pycnometer. Compressibility index (I) values of the microspheres were determined by measuring the initial volume (V0) and the final volume (V) after subjecting to 100 tapping in a graduated measuring cylinder using the equation. I = [1.b) Compressibility index (I): Carr¶s index was determined from powder volumes at the initial stage and after 1250 tappings to constant volume.

DSC measurement were done on a Mettler Toledo DSC 822c C/ min over a temperature range of 30 to 30000 C under an inert atmosphere flushed with nitrogen at a rate of 20 ml/min. 26 . DSC measurements were performed on differential scanning calorimeter (DSC DuPont 9900) with a thermal analyzer.4] THERMAL ANALYSIS Differential scanning calorimeter (DSC) DSC study was carried out to detect possible polymorphic transition during the crystallization process. Differential scanning calorimetry (DSC) was performed on ketoprofen and ketoprofen loaded microspheres.

x 100 Total Weight of Raw Material The percentage yield of each formulation was determined according to the total recoverable finalweight of microsphere and the total original weight of Indomethacin. %Yield= Total Weight of Microspheres -----------------------------------------.5] DETERMINATION OF PERCENTAGE YIELD The yield of microspheres was determined by the formula. 27 .

After suitable dilution. The drug content of Microspheres is estimated. Microspheres (50 mg) were triturated with 10 ml of water. sampleswere measured at particular max value of drug. 28 . Allowed to stand for 10 min withoccasional swirling and methanol was added to produce 100 ml.6] DRUG CONTENT Microspheres in a particular quantity were dissolve in a solvent and at specified max of drug . Drug content was determined from standard plot.

The drug concentration will be determin at particular max value of drug after suitable dilution.x 100 Weighed quantity of powder of microspheres 29 .7] DETERMINATION OF DRUG LOADING The drug loading was determined by UV Visible spectrophotometer. The microspheres were stirred with 100 ml particular solution as dissolution media (pH 7.40 phasphatebuffer )for 2hr. The readings were taken in triplicate. Drug loading (%) = M actual -----------------------------.

30 .8] INCORPORATION EFFICIENCY OF MICROSPHERES Incorporation efficiency (%) = M actual ---------------------. M actual is the actual drug content in weighed quantity of powder of microspheres & M theoretical is the theoretical amount of drug in microspheres calculated from the quantity added in the fabrication process.x 100 M theoretical Where.

The vials were shaken for two hours on mechanical shaker. The solution was filtered through Whatmann filter paper No. 31 .9] DETERMINATION OF SOLUBILITY The solubility of particular drug microspheres in specific solution as microspheres or microcapsule to be soluble in that particular environment (water and pH 7.4 phosphate buffer) was determined by taking excess quantity of microspheres in 50 ml to screw capped glass vials filled with water.1 and drug concentration wasbe determined at particular max value of drug.

32 . The readings were taken in triplicate. Dissolution medium was 900 ml 7.10] DISSOLUTION STUDIES OF MICROSPHERES The dissolution of microspheres is determined by using USP dissolution apparatus XXIV Type II. The amount of dissolved drug was determined using UV spectrophotometric method at specified max of particular drug.4 Phosphate buffer.

g.g.e. e. Immunomicrospheres Microsponges: Topical Porous Microspheres Imaging Surface modifide Microspheres . MTX.APPLICATION OF MICROSPHERES  Microspheres in Vaccine delivery .       Targeting of Drug Magnetic Microspheres. Mucosal Vaccine.

International Journal of Pharmaceutical Sciences Review and Research. Suppl 2. Gholap. March ± April 2010. 4] ASHWINI G KINI.635-636.International Journal of ChemTech Research. Article 015.. Issue: 1. International Journal of Drug Formulation & Research. ISSN: 0974-4290.REFERENCES 1] S.Jan-Feb. B... July-Sept 2009.142-143 3] Deore B. No. Volume 1. 2011. 2011.78 2] MUDIT DIXIT.Volume 3.3.V. Volume 2 (1).. Page no. Page no.232. 34 .Page no.page no. Volume 1.ISSN: 0975-1491.ISSN: 2229-5054. International Journal of Pharmacy and Pharmaceutical Sciences.

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