Microspheres Preparation and Evaluations.pdf

This explains the microsphere preparations and evaluation.

1. MICROSPHERES:
PREPARATION AND EVALUATIONS
Submitted By: Prachi Pandey*, Rahul Pal Submitted To: Mr. Arsh Chanana
M. Pharm (Pharmaceutics), IInd Sem.
Department of Pharmaceutics, NIMS Institute of Pharmacy, NIMS University, Jaipur, Rajasthan.
Microparticles are particles between 0.1 and
100 μm in size.Commercially available
microparticles are available in a wide variety of
materials including ceramics, glass, polymers,
and metals.

2. DEFINITION
Microspheresaresmallsphericalparticles,withdiameter
1µmto1000µm.
Theyaresphericalfreeflowingparticlesconsistingof
proteinsorsyntheticpolymerswhicharebiodegradablein
nature.
Microspheres representation

3. Microcapsulesarethoseinwhichentrappedsubstanceisdistinctlysurroundedbydistinctcapsulewall.
Micrometricsinwhichentrappedsubstanceisdispersedthroughoutthematrix.
CLASSIFICATION OF MICROSPHERES

4. CLASSIFICATION
Microspheres and Microcapsules Representation

5. MICROSPHERE TYPES
Types Description Application
Bio-adhesive Microsphere Prolong residence time Nasal Gentamycin
Floating Microsphere Bulk density less than gastric fluidNSAIDs, Antibiotics
Radioactive Microsphere Deliver high radiating dose to
target site
Diagnostics: Liver, spleen
Polymeric Microsphere Biodegredable and non-
biodegredable swells in aq media
Vaccine: Hepatitis
Local: Proteins
Magnetic Microsphere Localize the drug to release siteChemotherapeutics agents to liver

6. Improvebioavailability.
Provideconstantandprolongedtherapeuticeffect.
Provideconstantdrugconcentrationinblood.
Decreasedoseandtoxicity.
Protectthedrugfromenzymaticandphotolyticcleavagesoitisbestfordrugdeliveryofprotein.
Reducethedosingfrequencyandtherebyimprovethepatientcompliance
ADVANTAGES

7. DISADVANTAGE
Thecostismore.
Reproducibilityisless.
Processconditionslikechangeintemperature,pH,solventaddition,andevaporation/agitationmay
influencethestabilityofcoreparticles.
Degradationofproductduetoheat,hydrolysis,oxidation,solarradiationorbiologicalagents.

8. MARKETED PREPARATION OF
MICROSPHERES
Marketed Formulations of Microspheres
BRAND NAME COMPANY DRUG APPLICATION
Protonix
®
Wyeth
Pharmaceutical
Germany
Pantaprazole Gastric Ulcer
Altinac
®
Janssen Cilag
Pharmaceutical inc.
Tritinoin Skin regeneration
Lumason
®
Bracco Diagnostics
inc.
Sulfa Hexafluoride
lipid microsphere
Diagnosis and
Investigation

9. SingleEmulsionTechnique
DoubleEmulsionTechnique
SolventEvaporation
PhaseSeparationCoacervationTechnique
SprayDryingandSprayCongealing
SolventExtraction
Polymerization
METHODS OF PREPARATION

10. SINGLE EMULSION TECHNIQUE
Polymers in Aqueous Solution
Disperse in Organic Phase ( Oil/Chloroform)
Stir / Sonicate
Chemical crosslinking or heat denaturation
Microsphere in Organic Phase
Microsphere

11. DOUBLE EMULSION METHOD
Polymer in aqueous solution with drug
Disperse in organic phase
First Emulsion (W/O)
Multiple Emulsion
Microsphere in solution
Microsphere
Homogenization or sonication
Addition of Aqueous solution PVA
Addition of large aqueous solution
Separate , dry, wash

12. SOLVENT EVAPORATION
Core Material
Coating Polymer Solution
Core material disperse in liquid manufacturing vehical
phase
Evaporation of polymer solvent
Microsphere
Disperse
Agitate
Evaporate

13. PHASE SEPARATION COACERVATION
TECHNIQUE
Aquous / Organic solution in polymer
Drug disperse in polymer solution
Polymer rich globules
Microsphere in aquous / organic
phase
Microsphere
Add Drug
Phase separation induced by different means
Solidify
Separate, dry, wash

14. SPRAY DRYING / SPRAY CONGEALING
Polymer disperse in organic phase (acetone)
Drug disperse in polymer solution with high speed
homogenization
Atomizes in steam of hot air
Formation of small droplets
Microsphere
Solvent Evaporation

15. SPRAY DRYING / SPRAY CONGEALING
Polymer disperse in organic phase (acetone)
Coating Polymer Solution
Core material disperse in liquid manufacturing vehical
phase
Evaporation of polymer solvent
Microsphere
Separation by cyclone separator and drying by vacuum
drying

16. SOLVENT EXTRACTION

17. POLYMERIZATION

18. BULK POLYMERIZATION

19. SUSPENSION POLYMERIZATION

20. EMULSION POLYMERIZATION

21. INTERFACIAL POLYMERIZATION

22. 1)Particlesizeandshape:Themostwidelyused
procedurestovisualizemicroparticlesareconventional
lightmicroscopy(LM)andscanningelectronmicroscopy
(SEM).
2)Degradationbehavior:Thesurfacechemistryofthe
microspherescanbedeterminedusingtheelectron
spectroscopyforchemicalanalysis(ESCA).
EVALUATION

23. 3)Angleofrepose:Thepowdermasswasallowedtoflow
throughthefunnelorificekeptverticallytoaplanepaper
keptonthehorizontalsurface,givingaheapangleof
powderonpaper.Theangleofreposewascalculatedby
thefollowingequation
tan ϕ=h/r
Where,h&raretheheightbandradiusofthepowder
cone.
EVALUATION

24. EVALUATION
4)Bulkdensity:Bulkdensitywasobtainedbydividingthemass
ofpowderbythebulkvolumeincm³.Itwascalculatedbyusing
equation;
Bulk density volume = Mass of microspheres / Bulk
5)Tappeddensity:Itistheratiooftotalmassofthepowderto
thetappedvolumeofthepowder.Itisexpresseding/ml.
Tapped Density = Mass of the microspheres (W) / Tapped Volume of the
microspheres (Vf)
Density Apparatus

25. EVALUATION
6)Drugentrapmentefficiency:Itisthepercentageof
drugthatissuccessfullyentrappedwithinmicrospheres
Drugentrapmentefficiencycanbecalculatedusing
followingequation
% Entrapment = Actual content / Theoretical content x
100

26. EVALUATION
7)SwellingIndex:
ItisconductedinaphosphatebufferofpH6.8.Their
diameterismeasuredperiodicallybyusinglaser
particlesizedistributionanalyzeruntiltheywere
decreasedbyerosionanddissolution.
Swelling index= (mass of swollen microspheres -
mass of dry microspheres/mass of dried
microspheres) 100

27. EVALUATION
8)In-Vitromethods:
Releasestudiesfordifferenttypeofmicrospheresarecarriedoutby
usingphosphatebufferpH7.4,mostlybyrotatingpaddleapparatus.
Agitatedwith100rpm,sampleswerecollectedatspecifictimeintervals
andreplacedbysameamountandanalyzed.
Dissolution Apparatus

28. EVALUATION
9)Adhesionproperty:
Freshlycutpieceofpigintestineisused(5cmlong),cleanand
washitwithisotonicsalinesolution.
Accurateweightofmicrosphereswasplacedonmucosalsurface,
phosphatebufferofpH6.8iswarmedat37°cwasperistaltically
pumpedatarateof5ml/minoverthetissue.
Thedurationofcompletewashingmicrospheresfrompigintestine
wasrecorded.

29. APPLICATIONS
Ophthalmic Drug Delivery
Oral drug delivery
Gene delivery (RISPERDAL CONTRA risperidone)
Nasal drug delivery
Buccal drug delivery
Gastrointestinal drug delivery
Transdermal drug delivery (TDDS)
Prostate Cancer
Opoidscraving reducer (VIVITROL naltrexone)

30. REFERENCE
1.https://www.amazon.com/Microspheres-Microcapsules-Biotechnology-Preparation-
Applications/dp/9814316474
2.Dhadde,GurunathS.,etal."Areviewonmicrospheres:Types,methodofpreparation,characterizationand
application."AsianJournalofPharmacyandTechnology”11.2(2021):149-155.
3.Vasava,Drashti,JitendraPatel,andUmeshUpadhyay."Areviewarticleon:Microsphere."National
JournalofPharmaceuticalSciences2.2(2022):148-154.