M.PHARM_Week Tablet Compression Physics.docx

NOTES

1. 1

Tabletcompressionphysics
includes:
Transmissionofforcesduringcompressi
on
Distributionofforcesintablets
The effect of applied pressure on the
relativevolumeofthepowder
Interparticulat
e
forces
adhesion
an
d
cohesio
n
Tabletcompressionenergi
es
Mechanicalstrengthoftablets
Detaileddescriptionofthetoolsusedin
thesestudiesandworkingmethods.


PHYSICSOFTABLET COMPRESSION
Th
e
mai
n
criteri
a
fo
r
table
t
formulationsar
e:
Toformtabletswithoutstickingto
thepunchsurfacesandtothedie
wall, andcapping;
To compress the tablets with
acceptablemechanicalpropertiesi
n
termsofhardnessandfriability;
Tomeetpharmacopoeialimitsfor
tabletweightvariationandcontent
uniformity;
T
o
provid
e
appropriat
e
disintegrationtimeanddissolution
rateforthetablets.

2. 2


Manual hydroulic
presses(simulator)

3. 3

Ejection
force

Typicalpressure-
timeprofileobservedaccordingtothestage
s involved in tableting process

4. 4


HD:Duetopowder
anddiefriction
LD:Relatedtothe
forcetransmission
Compressionoflayers
withorwithoutcolored




A: Lubr.




B: Unlubr.

5. 5

relativevolumechange
of the powder vs.
pressure


filling-compression-compaction-decompression-ejection

6. 6


Heckelequation

7. 7

Tabletcompressionenergies







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??????=0

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8. 8



• Controlsofthestartingmaterials
TABLETTESTING

In-processandintermediateproductcontrolsat
variousstagesofmanufacturing
 Bulkdensity
 Flowproperties
 Moisturecontent
 Drug content
• Finishedproductcontrols
• Stability

Finishedproductcontrols
• Organolepticcontrols
• Thickness– diameter
• Uniformityofdosageunits
• Contentuniformity
• Weightvariation
• Mass uniformity
• Decompositionproductsandimpurities
• Hardness/tensilestrength
• Friability
• Disintegration
• Dissolution
• Microbialquality

9. 9

Invitrodissolutiontestsforimmediatereleasesolidoral
dosage forms are used:
(1) toassessthelot-to-lotqualityofadrugproduct;
(2) toassessthestability ofthedrugproduct;
(3) toensurecontinuingproductqualityandperformanceaftercertain
changes, such as changes in the formulation, the
manufacturing process, the site of manufacture, and the
scale-up of the manufacturing process; and
(4) to develop new formulations. In formulation development,
dissolution testing can aid in the selection of excipients, help
optimizethemanufacturingprocess,andenableformulationofthe
test product to match the release of the reference product.

10. 10

(EP6.0V1,Subdivisionoftablets,easeofintakeorposology
– uniformity of mass)
IMPORTANT...
Products that are not intended to be split, e.g. enteric coated
tablets, tablets which are film coated to maintain stability and
some modified release preparations, should not be split.
However, those modified release preparations using matrix
technology or using compressed film coated components could
be split.

11. 11








COATINGOFTABLE
TS:
Sugarcoating-
dragees
Filmcoatedtable
ts
Formulatio
ns
Manufacturingproces
ses

12. 12











• Increasedaestheticquality,
• Increasingpatientcompliance,
• Maskingofunpleasanttasteandsmellofdrugs,
• Easilyingestedbythepatient,
• Increasingthephysicalandchemicalstabilityofthedrug,
• Modificationofreleasekineticsofthedrugfromthe
dosage form,
• Providingentericreleasepropertiesforreleaseinthe
intestinal tract,
• Preventingdrugproductsfrombeingmixedregardingth
e manufacturer, facilitating coding,
• Protectionofthedrugfromthestomachandthestomach
fromthedrug.
Whyarethecoateddosageformspreferred?

13. 13

Thetypesofcores(substrate)forcoating


⚫ Crystals
⚫ Differenttypesofgranules
⚫ Pellets
⚫ Tablets
⚫ Softandhardgelatincapsule
s



Properties
⚫ Form/shapeandsize
⚫ Mechanicelstrengthand
friability
⚫ Formulation
⚫ Sensitivitytoheatand
moisture
⚫ Interactionswithcoating

14. 14

Therearesomedrawbacksofsugarcoating.
⚫ Due to the increase in diameter and weight (about 2
times or 30-100%increase),packagingandtransfer-
handlingfeeshave increased.
⚫ Thereisapossibilityofdamageduetothefragilityofthe
coating.
⚫ Specializedpersonnelforcoatingprocessarerequiredt
o achieve high aesthetic quality.
⚫ Thereisapolishingprocessthatmakescodingdifficultto
print.
⚫ Thereisacomplexapplicationwhichmakesthetransitionto
automation difficult: Various operations and functions
are used.

15. 15

Sugaralcohols
Invertsugar
Starchsugars
Excipientsusedintheformulationsofsugarcoating
• Sugars:



Preparationsof
sugarsolutions
Crystallization


Inversion








Maltitol

Mannitol
Xylitol
Sorbitol
Lactose
Glocose
Saccharose

16. 16

Gumacacia,agar-
agar,carboxymethylstarch,celluloseethers,dextrins,gelatin, PVA, PVP,
sodium alginate
Solubleorganicdyes,pigments, lakes
Otherexcipientsusedinthesugarcoatingformulation

Coatingagents:

Fillers:


Coloringagents:

Calciumcarbonate,talc,titaniumdioxide,calciumsulfate,calciumhydrogen
phosphate,calciumlactate

17. 17

Fruitessences,methylsalicylate,vanilla,cocoa,chocolate,condens
ed milk, caramel
Talc
• Flavors

• Lubricants


• Polishingagents


• Suspendingagents
Surfactants
Waxes,oils,resins

18. 18

Coatingprocessandcoatinglayers
Coatinglayer
s:
Uniform
coating
1.
2.
3.
4.
5.
Sealing(protectivecoatin
g)
Subcoating
Primin
g
coat
Correctivecoating(rossing/smoothin
g)
Rounding
layer
Colorcoatin
g
Polishing
Finishin
g
layer
Processstepsappliedforeachlayer:
 Applicationofcoatingformulation
 Mixingforhomogeneousdistributionof
formulation
 Drying