Microencapsulation I_241207_142720 (1).pdf

B.pharm 7th semester notes
Instrumental method of analysis
B pharmacy
Unit 2
IR spectroscopy
Fuorimetry
Analysis

1. UNIT-II
MICROENCAPSULATION
HTCOP 1

2. CONTENT
Thursday,07October2021 HTCOP 2
•Introduction
•Advantages&Disadvantages
•Microspheres/Microcapsules
•Methodsofmicroencapsulation
•Applications

3. INTRODUCTION
HTCOP 3

4. •Microencapsulationisatechniquebywhichsolid,liquidorgaseousactive
ingredientsarepackagedwithinasecondmaterialforthepurposeofshielding
theactiveingredientfromthesurroundingenvironment.
•Thustheactiveingredientisdesignatedasthecorematerialwhereasthe
surroundingmaterialformstheshell/coating material.
•Microencapsulationisdescribedasaprocessofenclosingmicronsized
particlesofsolidsordropletsofliquidsorgassesinaninertshell,whichin
turnisolatesandprotectsthemfromtheexternalenvironmentaswellas
controlthedrugreleaseprofile.
•Microencapsulatedparticleishavingless than 1 micron to several hundred microns
in size.
•diameterbetween3-800µm– Microparticles.
•Greater than 1000 µm known as Macroparticles
•differthemfromothertechnologiessuchasnanotechnologyandmacroparticle
intheirmorphologyandinternalstructure.HTCOP 4

5. ⚫Microencapsulationis a rapidlyexpanding technology.As a process,it isa
means ofapplying relativelythincoating tosmall particles ofsolid or
droplet ofliquids&dispersions.
⚫Microencapsulation provides themeans ofconverting liquidstosolids,of
alteringcolloidalandsurfaceproperties,ofprovidingenvironmental
protection,andofcontrollingthereleasecharacteristicsoravailabilityof
coatedmaterials.
HTCOP 5

6. REASONSFORMICROENCAPSULATION
HTCOP 6
⚫1.Themainreasonformicroencapsulationisforsustainedorprolongedreleaseof
thedrug
⚫2.ThistechniquehasbeenwidelyusedformaskingtheOrganoleptic
propertiesliketasteandodorofmanydrugsandthusimprovespatientcompliance
e.g.Paracetamol,nitrofurantoineformaskingthebittertaste.
⚫3.Byusingmicroencapsulationtechniquestheliquiddrugscanbeconvertedin
afreeflowingpowder.
⚫4.Thedrugssensitivetomoisture,lightandoxygencanbeprotectedby
microencapsulation.Forexample,Nifedipineisprotectedfromphotoinstability.
⚫5.Microencapsulationtechniqueisalsohelpfultopreventtheincompability
betweendrugs.
⚫6.Thedrugswhicharevolatileinnaturemayvaporizeatroomtemperature.
DrugslikeAspirinandpeppermintoilcanbepreventedbymicroencapsulation.

7. HTCOP 7
Mononuclear:
Containing the
shell around the
core.
Polynuclear:
Having many
cores enclosed
with in shell.
Matrix type:distributed
homogeneously into the
shell material.
Microcapsules can be classified on three types

8. ADVANTAGES
1.Maskingbittertasteofthe drug.E.g.Ofloxacin
2.Conversionofliquidtopseudosolid.E.g.Eprazinone
3.Reliablemeanstodeliverthedrugtothetargetsite&tomaintain
the desiredconcentrationatthesiteofinterest withoutuntoward
effects.
4.Reducethedosingfrequency&therebyimprovingpatient
compliance.
5.Injectedintothebodyduetosphericalshape&smallersize.
6.Reductionofhygroscopicity.
HTCOP 8

9. DISADVANTAGES
1.Itisanexpensiveprocess.
2.Requireskill.
3.Difficulttoobtain continuous&uniform film.
4.Possiblecross-reactionbetweencorematerial&shell.
5.Moreproductioncosts.
6.Moreskillandknowledgeisrequired.
HTCOP 9

11. FORMULATIONCONSIDERATIONS
HTCOP 11
1.Core Material
a.Solid
b.Liquid
2.Coating Material
a.Polymers
b.Waxes
c.Resins
d.Proteins
e.Polysaccharides
3. Vehicles
a.Aqueous
b.Non-aqueous

12. CoreMaterial
⚫Thecorematerial,definedasthespecificmaterialtobecoated,canbe
liquidorsolidinnature.Thecompositionofthecorematerialcanbe
varied,astheliquidcorecanincludedispersedand/ordissolved
material.
⚫Thesolidcorecanbeamixtureofactiveconstituents,stabilizers,
diluents,excipients,andrelease-rateretardantsoraccelerators.
⚫Theabilitytovarythecorematerialcomposition providesdefinite
flexibilityand utilizationofthischaracteristicoftenallowseffectual
designanddevelopmentofthedesiredmicrocapsuleproperties.
⚫Itisnotpossibletodiscuss,orevenlist,allofthepotentialcore
materialsandproductapplicationsthatareormaybeamenableto
microencapsulation.
HTCOP 12

13. CoreMaterial Characteristic
Property
Purposeof
encapsulation
Finalproduct
form
Acetaminophen Slightlywater
solubleproperty
Tastemask Tablet
IsletoflangerhansViablecells Sustainednormalisation
ofdiabeticcondition
Injectable
VitaminApalmitateNon-volatileliquidStabilizationto
oxidation
Drypowder
Methanol/Methyl
salicylatecamphor
mixture
VolatilesolutionReductionofvolatility;
Sustainedrelease
Lotion
PotassiumchlorideHighlywater
solublesolid
Reducedgastric
irritation
Liquidcrystals liquid Conversionofliquidto
solid/stabilization
Flexiblefilm
forthermal
mappingof
anatomy
HTCOP 13

14. CoatingMaterials
⚫Theselectionofthe appropriate coating material dictates,
toa major degree,theresultantphysical and
chemical propertiesof the microcapsules,and
consequently,thisselection mustbe given due
consideration.
⚫Thecoatingmaterialshouldbecapableofformingafilm
thatiscohesivewiththecorematerial;bechemically
compatibleandnonreactivewiththe corematerial.
⚫Providethedesiredcoatingproperties,suchasstrength,
flexibility,impermeability,opticalproperties,andstability.
HTCOP 14

15. ⚫Thecoatingmaterialsusedinmicroencapsulationmethodsare
amenableto someextent,toinsitu modification.
⚫Forexample,colorantsmaybeaddedtoachieveproductelegance
ormasking,or coatingsmaybeplasticizedorchemicallyaltered
throughcross-linking,for instance,toachievecontrolled
dissolutionorpermeability.
⚫Typicalcoatingproperties suchas cohesiveness,permeability,
moistureabsorption,solubility,stability,andclaritymustbe
consideredinselecting theproper microcapsulecoatingmaterial.
HTCOP 15

16. •Theuniquenessofmicrocapsulesintheirpropertiesanduse
involves theircharacteristicsmallness;theprotectivecoatingsthat
areappliedarequitethin.
•Although theactivecontentofmanymicroencapsulatedproducts
canvaryfromafewpercenttoover99%,theeffectivecoating
thicknessthatcanberealized,regardlessofthemethodof
applicationemployed,variesfromtenthsofamicrontoafew
hundredmicrons,dependingonthecoating-to-coreratioandthe
particlesize(surfacearea)ofthecorematerial.
HTCOP 16

17. CoatingMaterials
WaterSolubleResins–Gelatin,GumArabic,Starch,
Polyvinylpyrrolidone,CMC,HPMC,HEC
WaterInsoluble Resins–Ethyl cellulose, Cellulose Nitrate
Waxes&Lipids–Paraffin,carnauba,Beeswax,Stearicacid
Entericresins–Shellac,Celluloseacetatepthalate
HTCOP 17

19. RELEASEMECHANISM
1.DegradationControlledMonolithicsystem-
Drugdissolvedinmatrix&isdistributeduniformlythroughout.The
drugisstronglyattachtomatrix&isreleasedondegradationof
matrix.
2.DiffusionControlledMonolithicsystem-
Activeagentisreleasedbydiffusionpriortoorconcurrentwiththe
degradationofthepolymermatrix.Watersolubledrugmaydissolvein
theaqueousporenetworkorthroughtheaqueousporenetworks.
HTCOP 19

20. 3.DiffusionControlledReservoirSystem-
The active agent is released by diffusion prior to or concurrent with the
degradation of the polymer matrix. Rate of release also depends upon
where the polymer degrades by homogeneous or heterogonous.
mechanism
HTCOP 20
4.Erosion–Bulkandsurfaceerosion
Erosion of the coat due to PH and enzymatic hydrolysis causes drug release
with certain coat material like glyceryl monostearate, beeswax & stearyl
alcohol.

22. •METHODOLOGY
⚫AirSuspension
⚫Coacervation-Phaseseperation
⚫Multiorificecentrifugal
⚫PanCoating
⚫SolventEvaporation
⚫Spraydrying&congealing
HTCOP 22

23. METHODSOFMICROENCAPSULATION
⚫Physicalor Physico-mechanical
1.Airsuspension
2.Pancoating
3.Spraydrying
4.Multiorificecentrifugal
⚫Physico-chemical
1.Ionotropicgelation
2.Coacervation
⚫Chemical
1.SolventEvaporation
2.Polymerization
Thursday,30September2021 HTCOP 23

24. Microencapsulation
process
ApplicablecorematerialApproximateparticle
size(μm)
AirSuspension Solids 35-5000
Coacervation-Phase
seperation
Solids&liquids 2-5000
Multiorificecentrifugal Solids&liquids 1-5000
PanCoating Solids 600-5000
SolventEvaporation Solids-liquids 5-5000
Spraydrying&congealing Solids-liquids 6000
HTCOP 24

25. Air suspension:(Fluidized bed coating/ Wurster process)
" It consists of the dispersing of core materials in a supporting air
stream and the spray coating on the air suspended particles.
" Within the coating chamber, particulate core materials are suspended on
an upward moving air stream.
The chamber design and its operating parameters influence a recirculating
flow of the particles through the coating-zone portion of the coating-chamber.
During each pass through the coating-zone, the core material receives a coat
and this cyclic process is repeated depending on the purpose of micro
encapsulation.
The supporting air stream also serves to dry the product while it is being
encapsulated

30. PANCOATING
HTCOP 30

31. ⚫Themicroencapsulationofrelativelylargeparticlesbypanmethodshas
becomewidespreadinthepharmaceuticalindustry,andthetopicis
coveredindepthin“TabletCoating”.
⚫Withrespecttomicroencapsulation,solidparticlesgreaterthan
600micronsinsizearegenerallyconsideredessentialforeffective
coating,
⚫Theprocesshasbeenextensivelyemployedforthepreparationof
sustainedreleasepelletsandbeads.
⚫Medicamentsareusuallycoatedontovarioussphericalsubstratessuch
asnonpareilsugarseeds,andthencoatedwithprotectivelayersof
variouspolymers.
HTCOP 31

32. ⚫Inpractice,thecoatingisappliedasasolution,orasanatomizedspray,
tothedesiredsolidcorematerialinthecoatingpan.
⚫Usually,toremovethecoatingsolvent,warmairispassedoverthe
coatedmaterialsasthecoatingsarebeingappliedinthecoatingpans.In
somecases,finalsolventremovalisaccomplishedinadryingoven.
⚫Sustained-releasepelletsofDextroamphetaminesulfatehas
beenpreparedusingpancoatingmethodinwhichnonpareilseedsare
coated initiallywithDextroamphetaminesulfate,andthenwitha
release-rateretardingwax-fatcoating.
HTCOP 32

33. ⚫Theremainingproductisagaincoatedwiththewax-fatsolutionas
describedpreviously.
⚫Subsequently,onehalfofthematerialisremovedandtheremainderis
againcoatedtoyieldanadditionalcoatingofabout10%byweight.
⚫Thefourgroupsofpelletsarethenthoroughlymixedtoyieldthe
sustainedreleaseform.
HTCOP 33

34. SprayDryingandSpray Congealing
HTCOP 34

35. Spray Drying and Spray Congealing
Spray drying and spray congealing methods of microencapsulation are
almost similar.
Both the methods entail the dispersion of core material in a liquefied
coating agent and spraying or introducing the core coating mixture
into some environmental condition,
Whereby relatively rapid solidification of the coating is influenced.
The main difference in-between these two microencapsulation methods
are the means by which the coating solidification is carried out.
In spray drying method, the coating solidification is influenced by the
quick evaporation of a solvent, in which the coating material is
dissolved.

36. spray congealing
In spray congealing method, the coating solidification is
accomplished by thermal congealing of molten coating
material or solidifying dissolved coating by introducing
the coating core material mixture into a non-solvent.
Removal of the nonsolvent or solvent from the coated
product is then accomplished by sorption, extraction, or
evaporation techniques.

37. ⚫Inpractice,microencapsulationbyspraydryingisconductedbydispersing
acorematerialinacoatingsolution,inwhichthecoatingsubstanceis
dissolvedandinwhichthecorematerialisinsoluble.
⚫Atomizingthemixtureintoanairstream.Theair,usuallyheated,
suppliesthelatentheatofvaporizationrequiredtoremovethesolvent
fromthecoatingmaterial,thusformingthemicroencapsulatedproduct.
⚫Theequipmentcomponentsofastandardspraydryerincludean air
heater,atomizer,mainspraychamber,blowerorfan,cycloneand
product collector.
HTCOP 37

38. ⚫Processcontrolvariablesincludefeedmaterialpropertiessuchasviscosity,
uniformity,andconcentrationofcoreandcoatingmaterial,feedrate,
method ofatomization,andthedryingrate.
⚫Whichisnormallycontrolledbytheinletandoutlettemperaturesandtheair
streamsolventconcentration.
⚫Theprocessproducesmicrocapsulesapproachingasphericalstructureinthe
sizerangeof5to600microns.
⚫Characteristically,spray dryingyields productsoflow bulk density,owing
to theporousnatureofthecoatedparticles.
⚫Theprocessiscommonlyemployed inthemicroencapsulationof
liquid flavorsyieldingdry,free-flowingpowdersforuseinfoodsand
pharmaceuticals.
HTCOP 38

39. ⚫Microencapsulationbyspraycongealingcanbeaccomplishedwith
spraydryingequipmentwhentheprotectivecoatingisappliedasamelt.
⚫Generalprocessvariablesandconditionsarequitesimilartothose
alreadydescribed,exceptthatthecorematerialisdispersedinacoating
materialmeltratherthanacoatingsolution.
⚫Coatingsolidification(andmicroencapsulation)isaccomplishedby
sprayingthehotmixtureintoacoolairstream.
⚫Waxes,fattyacidsandalcohols,polymersandsugars,whicharesolids
atroomtemperaturebutmeltableatreasonabletemperatures,are
applicabletospray-congealingtechniques.
HTCOP 39

40. Coacervation
- Unique microencapsulation technology
-99 % payload achievable
-Controlled/ sustained release possibilities
Two Methods:
1. Simple coacervation 2. complex

41. Simple coacervation

42. Step 3: Rigidizing of coating materials done by the thermal,
crosslinking, desolvation techniques, to form a self supporting
microcapsule.

43. Simple coacervation

46. Complex coacervation induced in systems having two
dispersed hydrophilic colloids of opposite electric charges.
Neutralization of the overall positive charges on one of the
colloids by the negative charge on the other is used to bring
about separation of the polymer rich complex coacervate
phase.
Example: Gelatin –gum acacia system, complex coacervation
is possible only at values below the isoelectric point of gelatin.

47. SolventEvaporation
HTCOP 47

50. Single emulsion method:
Double emulsion method

51. Single emulsion method:
In Step 2 cross linking of dispersed globules is carried out by means of
heat or using chemical cross linkers like glutaraldehyde formaldehyde,
diacid chloride, terephthalate ect.,

52. Double emulsion method

53. ⚫Themicrocapsulecoatingisdissolvedinavolatilesolvent,whichis
immisciblewiththeliquidmanufacturingvehiclephase.
⚫Acorematerialtobemicroencapsulatedisdissolvedordispersedin
thecoatingpolymersolution.
⚫Withagitation,thecorecoatingmaterialmixtureisdispersedinthe
liquidmanufacturingvehiclephasetoobtaintheappropriatesize
microcapsule.
⚫Themixtureisthenheated(ifnecessary)toevaporatethesolventforthe
polymer.
⚫Inthecaseinwhichthecorematerialisdispersedinthepolymer
solution,polymershrinksaroundthecore.
HTCOP 53

54. ⚫Processvariableswouldinclude,butnotbelimitedto,methodsof
formingdispersions,evaporationrateofthesolventforthecoating
polymer,temperaturecycles,andagitationrates.
⚫Importantfactorsthatmustbeconsideredwhenpreparingmicrocapsules
bysolventevaporationtechniquesincludechoiceofvehiclephaseand
solventforthepolymercoating,asthesechoicesgreatlyinfluence
microcapsulepropertiesaswellasthechoiceofsolventrecovery
techniques.
⚫Thesolventevaporationtechniquetoproducemicrocapsulesisapplicable
toawidevarietyofliquidandsolidcorematerials.Thecore
materialsmaybeeitherwater-solubleorwater-insoluble
materials.
HTCOP 54

55. ⚫Inthecaseinwhichthecorematerialis dissolvedinthecoating
polymersolution,amatrix-typemicrocapsuleisformed.
⚫Onceallthesolventforthepolymerisevaporated,theliquidvehicle
temperatureisreduced(ifrequired)withcontinuedagitation.
⚫Atthisstage,themicrocapsulescanbeusedinsuspensionform,coated
ontosubstratesorisolatedaspowders.
HTCOP 55

56. IonotropicGelation
⚫Ionotropicgelationinvolvessimplytheinteractionofanionicpolymer
withoppositelychargeiontoinitiatecrosslinking.
⚫Ionotropicgelationisbasedontheabilityofpolyelectrolyte'stocrosslink
inthepresenceofcounterionstoformHydrogels.Since,theuseof
alginates,gellangum,chitosan,andcarboxymethylcelluloseforthe
encapsulationofdrugandevencells,Ionotropicgelationtechniquehas
beenwidelyusedforthispurpose.
⚫Thethreedimensionalstructureandpresenceofothergroupsinfluence
theabilityofcations(oranions)toconjugatewithanionic(orcationic)
functionalitiesandsomekindofselectivityisfound.

58. •The natural polyelectrolyte's inspite, having a property of coating on
the drug core and acts as release rate retardants contains certain
anions on their chemical structure.
•These anions forms meshwork structure by combining with the
polyvalent cations and induce gelation by binding mainly to the anion
blocks.
•The hydrogel beads are produced by dropping a drug-loaded
polymeric solution into the aqueous solution of polyvalent cations.
•The cations diffuses into the drug-loaded polymeric drops, forming a
three dimensional lattice of ionically crossed linked moiety.
• Biomolecules can also be loaded into these hydrogel beads under mild
conditions to retain their three dimensional structure.

59. Polymerization
HTCOP 59

60. 1.In this technique the capsule shell will be formed at or on the surface of
the droplet or particle by polymerization of the reactive monomers.
2.The substances used are multifunctional monomers.
3.Generally used monomers include multifunctional isocyanates and
multifunctional acid chlorides.
4.These will be used either individually or in combination.
5.The multifunctional monomer dissolved in liquid core material and it will
be dispersed in aqueous phase containing dispersing agent.
6.A co-reactant multifunctional amine will be added to the mixture.
7.This results in rapid polymerization at interface and generation of capsule
shell takes place .
8.A polyurea shell will be formed when isocyanates reacts with amine,
polynylon or polyamide shell will be formed when acid chloride reacts with
amine.
9.When isocyanates reacts with hydroxyl containing monomer it produces a
polyurethane shell.

61. •In interfacial cross-linking method of microencapsulation, the
small bifunctional monomer containing active hydrogen atoms is
replaced by a bio sourced polymer, like a protein.
•When the reaction is performed at the interface of an emulsion, the
acid chloride reacts with the various functional groups of the
protein, leading to the formation of a membrane.
1.Interfacialpolymerization(IFP)

62. In-Situ Polymerization
1.The capsule shell formation occurs because of polymerization of
monomers added to the encapsulation reactor.
2.In this process no reactive agents are added to the core material,
polymerization occurs exclusively in the continuous phase and on the
side of the interface formed by the dispersed core material and
continuous phase.
3.Initially a low molecular weight prepolymer will be formed, as time
goes on the prepolymer grows in size, it deposits on the surface of the
dispersed core material there by generating a solid capsule shell.
Example: Encapsulation of cellulose fibers with polyethylene
(Ethylene monomers)

64. Multiorific-centrifugation
•Utilizes the centrifugal forces to hurl a core particle through an
enveloping membrane
•Various processing variables of multiorific-centrifugation method include
Rotational speed of the cylinder, Flow rate of the core and coating
materials, and Concentration, viscosity and surface tension of the core
material.
•The multiorifice-centrifugal method is capable for microencapsulating
liquids and solids of varied size ranges with diverse coating materials. "
The encapsulated product can be supplied as slurry in the hardening
media as dry powder.

66. PharmaceuticalApplications
HTCOP 66
⚫Gene therapy and in VaccinesfortreatingAIDS,tumors,canceranddiabetes.
⚫ThedeliveryofcorrectivegenesequencesintheformofplasmidDNAcould
provideconvenienttherapyforanumberofgeneticdiseasessuchascystic
fibrosisandhemophilia.
⚫WorldsfirstCephalexin(Ceff-ER)andCefadroxil(OdoxilOD)antibiotic
tabletsfortreatmentofbacterialinfections.
⚫AspirincontrolledreleaseversionZORprinCRtabletsareusedforrelieving
arthritissymptoms.
Applications of Microencapsulation

68. 1.Improvesflowproperty,Thiamine.
2.Maskunpleasanttaste&odour,castoroil.
3.Reducethevolatilityofmaterials,methylsalicylate.
4.Toreducegastricirritation,indomethacin.
5.Usedtoaidintheadditionofoilymedicinestotableteddosageforms.
6.Improvedflowproperties.
e.g.The non-flowablemulticomponent solidmixture ofniacin,riboflavin,
andthiaminehydrochlorideandironphosphatemaybe
encapsulatedandmadedirectlyintotablets.
HTCOP 68

69. 6.Toprotectdrugsfromenvironmentalhazardssuchashumidity,light,
oxygenorheat.eg.vitaminAandKhavebeenshowntobeprotectedfrom
moistureandoxygen throughmicroencapsulation.
7.Theseparationsofincompatiblesubstances,
e.g.Pharmaceuticaleutectics.
8.Thestabilityenhancementofincompatibleaspirin,chlorpheniramine
Maleatemixturewasaccomplishedbymicroencapsulatingbothofthem
beforemixing.
HTCOP 69

70. Examplesofmarketedproducts
1.SandostastinLAR(Novartis pharma),microcapsulesforsuspension,
Octreotideacetate(API)
2.M-Eslon (EthylpharmaIndustries), capsule with sustained release
microcapsule,Morphinehelp torelievepain incancerous patients.
HTCOP 70

71. FoodIndustry
⚫Addingingredientstofoodproductstoimprovenutritional
valuecan
•compromisetheirtaste,color,textureandaroma.
⚫Sometimestheyslowlydegradeandlosetheiractivity,or
become hazardousbyoxidationreactions.
⚫Ingredientscan alsoreactwithcomponentspresentinthefood
system, which maylimitbioavailability.
HTCOP 71

72. Catalysis
HTCOP 72
⚫Safehandling,easyrecovery,reuseanddisposalatanacceptableeconomic
cost.
⚫Metalspeciessuchaspalladium(II)acetateandosmiumtetroxidehave
beenencapsulatedinpolyureamicrocapsulesandusedsuccessfullyas
recoverableandreusablecatalystswithoutsignificantleachingandlossof
activity.

73. AgriculturalApplications
⚫Reduceinsectpopulationsbydisruptingtheirmatingprocess.
⚫Protectsthepheromonefromoxidation andlightduringstorageand
release.
HTCOP 73

74. Evaluation
1.Sieve analysis
2.Atomic force microscopy: surface morphology
3.Density :using multi volume pycnometer.
4.FourierTransform InfraredSpectroscopy
5.DrugEntrapmentefficiency:
% entrapment =(actual content/theorectal content) x 100
Percentageyield
6. Angle of contact: nature of microspheres in terms of hydrophilicity &
hydrophobicity. Measured at solid/water/ait interface
7. Swellingindex
8. In vitro release studies: beaker method, dissolution apparatus.
HTCOP 74