Seminar on Micro Sphere by Rajat & Vivek

8/2/2019 Seminar on Micro Sphere by Rajat & Vivek

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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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Seminar on Micro Sphere by Rajat & Vivek