seminar on micro sphere by rajat & vivek
TRANSCRIPT
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-:CONTENTS OF SEMINAR :-
Introduction
Advantage
Polymar used for preparation
General Method of Preparation
Characterization of Microspheres.
Application of Microspheres
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-:INTRODUCTION:-
Microspheres are solid , approximately spherical
particles ranging1-1000m in size.
They are made up ofpolymeric substance in
which the drug is dispersed through out the
microspheres matrix.
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ADVANTAGE OF MICROSPHERES:
They facilitate accurate delivery ofsmall 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
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POLYMER USED FOR MICROSPHERES
PREPARATION:
BiodegradablePolyme:
Lactides&Glycolides andtheir copolymer
Polyanhydrides
Polycynoacrylates
NON BiodegradablePolyme:
Poly methyl methacrylate
Acrolein
Epoxy Polymer
Glycidyl methacrylate
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THE ADMINISTRATION PARAMETERS THAT CAN BE
SATISFACTORILY CONTROLLED ARE AS FOLLOW:
Taste and odour masking
Conversion of oil and other liquids, facilitatingease of handling
Protaction of the drug from the environment
Delay ofvolatillisation
Freedom from incompatibilities between drug and
excipients,especially the buffers
Improvement offlow properties
Safe handling of test masking
Dis ersion of water insoluble substance in a ueous media
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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
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A) SINGLE EMULSION TECHNIQUE
Aqous solution /suspension of polymer(natural polymer)
stirring / sonication
dispersion in orgenic phase oil/chcl3cross linking
Heat denaturation chemical crosslinking
(by adding dispersion (butanol,HCHO,Glutaraldehyde)
To heated oil)
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MICROSPHERES IN ORG.PHASE MICROSPHERES IN
ORG.PHASE
CENTRIFUGATION,WASHING,SEPARATION
MICROSPHERES
MICROSPHERES IN ORG.PHASE MICROSPHERES IN
ORG.PHASE
CENTRIFUGATION,WASHING,SEPARATION
MICROSPHERES
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B) DOUBLE EMULSIONTECHNIQUE
Aqueous solution of polymer
dispersion in oil/orgenic phase, vigorous homogenisation(sonication)
Primary emulsion(w/o)
addition of aqueous solution of PVA
W/O/W multipal emulsion
addition of large aq. Phase
MICROSPHERES in solution
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SEPARATION,WASHING, DRYING
MICROSPHERES
SEPARATION,WASHING, DRYING
MICROSPHERES
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C)POLYMERIZATION
A)NormalPolymerization:Normal Polymerization is done by bulk, suspension, pption,emulsion and
polymerization process.
1.
Bulkpolymerization:Monomer Bioactive material Initiator
Heated to initiate polymerization
Initiator accelerate rate of raction
Polymer(Block)
Moulded/fragmented
MICROSPHERES
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B)SUSPENSIONPOLYMERIZATION
Monomer Bioactive material Initiator
Dispersion in water and stebilizer
Droplet
Vigorous ,Aggitation Polymerization by Heat
Hardened microspheres
Separation&Drying
MICROSP HERES
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3) EMULSIONPOLYMERISATIONMonomer/ Aq.Solution ofNaOH,
Bioactive material Initiator, Surfactant , Stabilizer
Dispersion with vigorous stirring
Micellar sol. Of Polymer in aqueous medium
Polymarization
Microspheres formation
MICROSPHERES
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E)SPRAY DRYING
Polymer dissolve in volatile organic solvent(acetone,dichloromethane)
Drugdispersed 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
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CHARACTERIZATION PROPERTIES OF
MICROSPHERES
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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
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8]I
ncorporation efficiency of microspheres
9] Determination of solubility
10] Dissolution studies of microspheres
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1] PARTICLE SIZE ANALYSIS
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Particle size of recrystallized sample, pure samples, spays driedmicrospheres were determined by microscopic method using
calibrated ocular micrometer.
A microscopical image analysis technique for determination of
particle size was applied. The morphology and particle sizes were
determined in a Digital microscope equipped with a 1/3CCD
camera imaging accessory
The microspheres were dispersed on a microscope slide. Amicroscopical field was scanned by video camera. The images of
the scanned field are analyzed by the softwar.
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] SCANNING ELECTRON MICROSCOPY (SEM) STUDY
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The morphology of microspheres was examined by scanning
election microscopy. A small amount of powder was spread on an
aluminum stub, which was placed latter gold sputtering in san SEM
chamber.
Photographs were taken at an acceleration voltages of 20 KV
electron beam. Obtained photograph to identify and confirm
spherical nature and Surface topography of the crystals.
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3] FLOW PROPERTIES
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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.
Static angle of repose was measured according to the fixedfunnel and free standing cone method of Banker and Anderson.
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), H,
above graph paper placed on a flat horizontal surface. The
microspheres were carefully poured through the funnel until the
apex of the conical pile so formed just reached the tip of the
funnel.
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tan = H/ R
or
= tan-1 (H/ R)
where = the angle of repose
Thus, the R being the radius of the base of the microspheres
conical pile:
.
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b) Compressibility index (I):
Carrs index was determined from powder volumes at the
initial stage and after1250 tappings to constant volume.
Compressibility index (I) values of the microspheres were
determined by measuring the initial volume (V0) and the finalvolume (V) after subjecting to 100 tapping in a graduated
measuring cylinder using the equation.
I = [1- (V/V0)] x 100
Apparent particle densities of microsphere were measured
using a Pycnometer.
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4] THERMAL ANALYSIS
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Differential scanning calorimeter (DSC)
DSC study was carried out to detect possible polymorphic
transition during the crystallization process. DSC measurements
were performed on differential scanning calorimeter (DSC DuPont
9900) with a thermal analyzer.
Differential scanning calorimetry (DSC) was performed on
ketoprofen and ketoprofen loaded microspheres. DSC measurement
were done on aM
ettler Toledo DSC8
22c C/ min over atemperature range of 30 to 30000 C under an inert atmosphere
flushed with nitrogen at a rate of 20 ml/min.
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5] DETERMINATION OF PERCENTAGE YIELD
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The yield of microspheres was determined by the formula,
%Yield= Total Weight ofMicrospheres
------------------------------------------ x 100Total 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 ofIndomethacin.
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6] DRUG CONTENT
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Microspheres in a particular quantity were dissolve in a solvent
and at specified max of drug . The drug content ofMicrospheres is
estimated.
Microspheres (50 mg) were triturated with 10 ml of water.
Allowed to stand for10 min withoccasional swirling and methanol
was added to produce 100 ml. After suitable dilution, sampleswere
measured at particular max value of drug. Drug content was
determined from standard plot.
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7] DETERMINATION OF DRUG LOADING
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The drug loading was determined by UVVisible spectrophotometer.
The microspheres were stirred with 100 ml particular solution as
dissolution media (pH 7.40 phasphatebuffer )for 2hr. The drug
concentration will be determin at particular max value of drug aftersuitable dilution. The readings were taken in triplicate.
Drug loading (%) = M actual
------------------------------ x 100
Weighed quantity ofpowder of microspheres
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8] INCORPORATION EFFICIENCY OF MICROSPHERES
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Incorporation efficiency (%) = M actual
---------------------- x 100
M theoretical
Where,
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.
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9] DETERMINATION OF SOLUBILITY
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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
cappedglass vials filled with water. The vials were shaken for two hours on
mechanical shaker. The solution was filtered through Whatmann
filter paper No.1 and drug concentration wasbe determined at
particular max value of drug.
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10] DISSOLUTION STUDIES OF MICROSPHERES
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The dissolution of microspheres is determined by using USP
dissolution apparatus XXIV Type II. Dissolution medium was 900
ml 7.4 Phosphate buffer. The amount of dissolved drug was
determined using UV spectrophotometric method at specified
max of particular drug. The readings were taken in triplicate.
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APPLICATION OF MICROSPHERES
Microspheres in Vaccine delivery ,e.g. Mucosal
Vaccine.
Targeting of DrugMagnetic Microspheres, e.g. MTX.
Immunomicrospheres
Microsponges: Topical Porous Microspheres
Imaging
Surface modifide Microspheres
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REFERENCES
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1] S. B. Gholap,International Journal of Pharmaceutical Sciences
Review and Research, Issue: 1, Volume 1, March April 2010;
Article 015,Page no.- 78
2] MUDIT DIXIT, International Journal of Drug Formulation &
Research,ISSN: 2229-5054, Volume 2 (1),Jan-Feb. 2011, Pageno.- 142-143
3] Deore B.V.,International Journal of ChemTech Research, ISSN:
0974-4290, Volume 1, No.3, July-Sept 2009,page no.- 635-636.
4] ASHWINI
G KINI
,International Journal of Pharmacy andPharmaceutical Sciences,ISSN: 0975-1491,Volume 3, Suppl 2,
2011, Page no- 232.
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THANK YOU