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Ak1 CNL nAkD Ak1 CNL nAkD CASULLS CASULLS

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CuLllne
W lnLroducLlon
W 8aw maLerlals
W ManufacLure
mpLy capsule properLles
Capsule fllllng
Capsule slzes
Capsule shell fllllng
Capsulefllllng machlnes
elleL fllllng
1ableL fllllng
Sermlsolld and llquld fllllng
lormulaLlon
2
IN1kCDUC1ICN
W 1he word capsule ls derlved from Lhe LaLln nff meanlng a
small box
W ln pharmacy Lhe word ls used Lo descrlbe an edlble package
made from gelaLln or oLher sulLable maLerlal whlch ls fllled
wlLh medlclnes Lo produce a unlL dosage malnly for oral use
W 1here are Lwo Lypes of capsule
Pard Lwoplece
SofL oneplece
3
Cap
8ody
Pard gelaLln capsule
4
lnLroducLlon
SofL gelaLln capsule
3
dvanLages
1he use of capsules avolds many unlL operaLlons
8apld drug release posslble
llexlblllLy of formulaLlon
aslly compounded
Sealed PCCs are good barrlers Lo aLmospherlc oxygen
6
dvanLages
1he sLablllLy of LherapeuLlc agenLs may be lmproved ln a
capsule formulaLlon
leganL appearance and shape
asy Lo swallow
Mlnlmum exclplenLs are requlred
7
lsadvanLages
very bulky maLerlals are a problem
lllllng equlpmenL slower Lhan LableLlng
Concern over malnLalnlng proper shell molsLure conLenL
Shell should have molsLure conLenL of 1313
lf Loo dry become brlLLle/easlly fracLured
lL Loo molsL become Loo sofL and can geL sLlcky
8
-oL sulLable for hlghly soluble subsLances llke poLasslum
chlorlde
-oL sulLable for hlghly efflorescenL or dellquescenL maLerlals
Speclal condlLlons are requlred for sLorage
9
kAW MA1LkIALS
CelaLln
WaLer
ColouranLs
CpLlonal maLerlals
reservaLlves
WeLLlng agenL
W 8ecenL years hard capsules have been manufacLured also
from hydroxypropyl meLhylcellulose
10
W CelaLln was Lhe flrsL maLerlal used for Lhe manufacLure of
capsules because of lLs unlque properLles
W lL ls ldeal because
lL ls edlble
soluble aL body LemperaLure
forms sLrong Lhln fllms
undergoes a gelaLlon process aL LemperaLures [usL above
amblenL
kAW MA1LkIALS
11
Ge|at|n and A|ternat|ve Mater|a|s
Ge|at|n
|s a mater|a| der|ved from co||agen a natura|
prote|nwh|ch |s
|s a f|brous mater|a| that occurs |n the sk|n bones
and connect|ve t|ssues of an|ma|s
It |s |nso|ub|e |n water and |s so|ub|||zed by hydro|ys|s
are obta|ned pr|mar||y from bov|ne bones or porc|ne
sk|ns
kAW MA1LkIALS
12
W Ge|at|n
kAW MA1LkIALS
Ac|d hydro|ys|s
sk|ns co||agen
1ype A ge|at|n
1ype 8 ge|at|n bov|ne bones
8as|c hydro|ys|s
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14
fLer hydrolysls
kAW MA1LkIALS
exLracLlon
evaporaLlon
coollng
drylng
exLracLed from Lhe Lread
maLerlal uslng hoL waLer
1he resulLlng weak soluLlon
of gelaLln ls concenLraLed ln
a serles of evaporaLors
Lhen chllled Lo form a gel
1he gel ls Lhen drled ln a
fluldlzedbed sysLem
13
W LlmlLaLlon of gelaLln
Lhere are cerLaln rellglous or dleLary resLrlcLlons on lLs
use
8ovlne Sponglform ncephalopaLhy
CelaLln lLernaLlve MaLerlals
hydroxypropyl meLhylcellulose (PMC )
molsLure conLenL ls much lower
kAW MA1LkIALS
16
W ColoranLs
Commonly varlous soluble synLheLlc dyes (coal Lar dyes") and
lnsoluble plgmenLs are used
Commonly used plgmenLs are Lhe lron oxldes
W Cpaqulng genLs
1lLanlum dloxlde may be lncluded Lo render Lhe shell opaque
W reservaLlves
When preservaLlves are employed parabens are ofLen selecLed
W rocess alds
sodlum lauryl sulphaLe
as a weLLlng agenL
Lo ensure unlformly coverlng moulds by gelaLln
W WaLer
kAW MA1LkIALS
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CASULL SnLLL MANUIAC1UkL
llg capsule manufacLurlng machlne ) CelaLln soluLlon sLorage Lank
8) dlp pan C) drylng kllns ) auLomaLlc secLlon
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CASULL SnLLL MANUIAC1UkL
[o|n|ng
tr|mm|ng
str|pp|ng
Dry|ng
kotat|on
D|pp|ng Ge|at|n So|ut|on
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20
CASULL MANUIAC1UkL
Ge|at|n So|ut|on
8aw gelaLln and waLer are mlxed ln Lhe
raLlo of 1 2 and processed aL preclse
LemperaLure
D|pp|ng
alrs of sLalnless sLeel plns are dlpped
lnLo Lhe dlpplng soluLlon Lo
slmulLaneously form Lhe caps and
bodles
CASULL SnLLL MANUIAC1UkL
21
CASULL SnLLL MANUIAC1UkL
kotat|on Whlle ralslng Lhey are roLaLed for
requlred dlsLrlbuLlon of gelaLln on Lhe
plns
Dry|ng
rylng ls done malnly be dehumldlflcaLlon by
passlng large volumes of dry alr over Lhe plns Cnly a
LemperaLure elevaLlon a few degrees ls permlsslble
Lo prevenL fllm melLlng
22
CASULL SnLLL MANUIAC1UkL
str|pp|ng
str|ppers remove the dr|ed ha|ves of capsu|es
from the p|ns and p|ace them |nto the co||ets
for further operat|ons
tr|mm|ng
Caps and body ha|ves are tr|mmed to narrow
to|erance as per standards 1he cutt|ng are
vacuumed away and co||ected |n separate drums
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CASULL SnLLL MANUIAC1UkL
[o|n|ng
1he capsu|e ha|ves move to the centre of the
mach|ne and enter the [o|ner b|ocks Io|ned
capsu|es are then pushed on to the conveyor be|t
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Capsule quality is monitored throughout the production
process including size, moisture content, single wall
thickness, and color.
23
Capsules are sorted and visually inspected on
specially designed !nspection Stations
26
#erfect capsules are imprinted with the client logo on
highspeed
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mpty capsule property
mpty capsule contain a significant amount of water that
acts as plasticizer for the gelatin film and is essential for
their function.
The standard moisture content specification of HCC is
between 13 to 16 w/w.
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CASULL IILLING
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CASULL IILLING
Capsu|e f||| capac|ty
3 4 3 2 1 0 00
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CASULL IILLING
Capsu|e f||| capac|ty
1he flll capaclLy of a hard capsule ls dependenL on
physlcal slze of Lhe capsule
Lype of formulaLlon
doslng mechanlsm on Lhe fllllng devlce
llll welghL 8ody volume x 1apped bulk denslLy
CASULL IILLING
31
1?S Cl M18lL lC8 llLLl-C l- 1C P8 CL1l-
CSuLS
Dry solids Semisolids Liquids
Powder
Pellets
Granules
Tablets
ThermosoItening
mixtures
Thixotropic mixtures
Pastes
Oily liquids
Non-aqueous liquids
1he fllllng maLerlal musL be compaLlble wlLh Lhe gelaLln shell
dellquescenL or hygroscoplc maLerlals cannoL be used
Lhey cannoL be used for molsLure senslLlve drugs
ll lngredlenLs need Lo be free of even Lrace amounLs of
formaldehyde Lo mlnlmlze cross llnklng of gelaLln
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POWDERS
TabIets
PeIIets
GranuIes
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apIets
Paste
Liquids
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lngredlenL 8
Capsu|e she|| f||||ng
lngredlenL
mpLy capsules owder blend Mlxlng
lngredlenL c
owder b|end M|x|ng
Capsule flller
Machlne
Capsu|e
c|eaner]deduster
capsule lnspecLlon screen
ackaglng
33
36
Capsule shell fllllng
Loadlng of empty capsu|es ln Lo Lhe hopper
ass down Lhrough Lube Lo a rect|f|cat|on secLlon
1he bodles are Lhen passed under Lhe dos|ng mechan|sm
I|||ed w|th mater|a|s
MeLal flngers push Lhe bodles up lnLo Lhem Lo re[o|n Lhe Lwo parLs
1he body ls separated from Lhe cap by means of sucLlon
37
Capsule shell fllllng
8ecLlflcaLlon
capsule separaLlon
fllllng
closure of Lhe capsule
e[ecLlon of Lhe fllled and closed
capsule from Lhe machlne
38
Capsule fllllng machlnes
W lllllng machlnes are dlfferenLlaLed by
Lhe way they measure the dose of maLerlal ln Lo Lhe
capsule body
range |n capac|ty from bench Lop Lo hlgh ouLpuL
lndusLrlal from manua| Lo fu||y automated machlnes
W 1hose LhaL rely on Lhe volume of Lhe shell are known as
capsule dependenL whereas capsule lndependenL forms
measure Lhe quanLlLy Lo be fllled ln a separaLe operaLlon
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8enchsca|e f||||ng
8equlred for fllllng small quanLlLles of capsules (3010000)
used ln communlLy pharmacy or ln hosplLal pharmacyor
ln lndusLrlal for speclal prescrlpLlons or Lrlals
conslsL of seLs of plasLlc plaLes LhaL have seLs of holes
drllled ln Lhem correspondlng Lo Lhe slze of Lhe capsule
LhaL can be fllled
1he capsules are fed lnLo Lhe plaLes elLher manually one
aL a Llme or ln groups uslng a feedlng devlce
lllllng of powder formulaLlon
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8enchscale fllllng
1he bodles are clamped ln Lhe boLLom plaLe and Lhe Lop
plaLe removed whlch separaLes Lhe caps from Lhe body
1he bodles are released so LhaL Lhey slL below Lhe Lop of
Lhe boLLom plaLe
owder or pelleLs are fllled lnLo Lhe capsules by spreadlng
maLerlal over Lhe body plaLe
Capsule fllllng machlnes
41
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lndusLrlalscale fllllng
Come ln greaL varleLy of shapes and slzes
1hese machlnes may be elLher semlauLomaLlc or fully
auLomaLlc
Sem|Automat|c Mach|nes
requlre an operaLor Lo be ln aLLendance aL all Llmes
ependlng on Lhe sklll of Lhe operaLor Lhe formulaLlon
and Lhe slze of Lhe capsule belng fllled Lhese machlnes are
capable of fllllng as many as 120000 160000 capsules ln
an 8hour shlfL
Capsule fllllng machlnes
43
Iu||y Automat|c Mach|nes
machlnes may be classlfled as elLher lnLermlLLenL or
conLlnuous moLlon machlnes
lnLermlLLenL machlnes exhlblL an lnLerrupLed fllllng
sequence
ConLlnuous moLlon machlnes execuLe Lhese funcLlons ln a
conLlnuous cycle
Capsule fllllng machlnes may vary w|de|y |n the|r
eng|neer|ng des|gn Lhe maln dlfference beLween Lhem
from a formulaLlon polnL of vlew ls the means by wh|ch
the formu|at|on |s dosed |nto the capsu|es
Capsule fllllng machlnes
44
W lour maln doslng meLhods may be ldenLlfled for powder
fllllng
1 uger llll rlnclple
Was Lhe flrsL successful lndusLrlal fllllng machlne
1he empLy capsule bodles are held ln a fllllng rlng whlch
roLaLes under Lhe powder hopper
1he flll of Lhe capsules ls prlmarlly volumeLrlc
8ecause Lhe auger mounLed ln Lhe hopper roLaLes aL a
consLanL raLe Lhe raLe of dellvery of powder Lo Lhe
capsules Lends Lo be consLanL
ConsequenLly Lhe ma[or conLrol over flll welghL ls Lhe
raLe of roLaLlon of Lhe fllllng rlng under Lhe hopper
Capsule fllllng machlnes
43
1ype 8 semlauLomaLlc capsulefllllng machlne
46
2 vlbraLory llll rlnclple
used a vlbraLlng plaLe ln Lhe powder
hopper
1he bodles ln Lhelr holders passed
under Lhe hopper
1he cavlLles wlLh Lhe bodles were
overfllled and ralsed up agalnsL a meLal
plaLe Lo push Lhe excess lnslde powder
lnslde
1hls sysLem works well wlLh dense free
flowlng maLerlal
Capsule fllllng machlnes
1he Csaka machlnes
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48
3lsLon1amp rlnclple
MosL capsules are fllled on plsLonLamp machlnes
1hese are fully auLomaLlc flllers ln whlch plsLons or Lamplng
plns llghLly compress Lhe lndlvldual doses of powders lnLo
plugs (someLlmes referred Lo as slugs") and e[ecL Lhe plugs
lnLo Lhe empLy capsule bodles
1he compresslon forces are low ofLen ln Lhe range of 30 200
- or abouL 30 100fold less Lhan Lyplcal LableL compresslon
forces
Capsule fllllng machlnes
49
3lsLon1amp rlnclple
W 1here are Lwo Lypes of plsLonLamp flllers dosaLor
machlnes and doslngdlsc machlnes
A dosator mach|nes (the dos|ng tube)
Lube ls Lhe mosL wldely used and lL orlglnaLed ln lLaly
1he p|ug |s formed |ns|de a tube wlLh a moveable plsLon
LhaL conLrols Lhe doslng volume and applles a force Lo form
Lhe plug
Capsule fllllng machlnes
30
lagrammaLlc represenLaLlon of Lhe dosaLor fllllng prlnclple
31
D|agrammat|c representat|on of the dosator f||||ng pr|nc|p|e
32
oslnglsc Machlnes
form a plug ln a slmllar buL dlfferenL manner
1he doslng dlsc whlch forms Lhe base of Lhe powder
hopper has up Lo slx seLs of machlned holes
ln a holder above Lhe powder hopper Lhere are seLs of
sLalnless sLeel Lamplng flngers correspondlng Lo Lhe holes
ln Lhe dlsk
Lhe Lamplng flngers are lowered lnLo Lhe powder bed
Capsule fllllng machlnes
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1he flngers are seL Lo dlfferenL levels and Lhey peneLraLe lnLo
Lhe plaLe and consolldaLe Lhe powder ln Lhe cavlLles lnLo
plugs
1he doslng dlsks are produced ln a range of Lhlcknesses for
each slze of capsule
Lhe selecLlon of Lhe correcL Lhlckness of dlsk ls lmporLanL
because lf Lhe flll welghL cannoL be achleved
Capsule fllllng machlnes
34
D|agrammat|c representat|on of the dos|ng d|sc f||||ng pr|nc|p|e
SchemaLlc dlagram of a doslng dlsc and Lamplng
flnger sysLem (8osch Ckl machlne) () overload rellef
sprlng (8) LampdepLh ad[usLer (C) Lamplng flnger ()
powder hopper () powder bed (l) doslng dlsc (C) sucLlon
(P) supporL plaLe (l) e[ecLlon ad[usLer (!) gulde block (k)
Lransfer block (L) capsule body ln bushlng and (M) powder
plug
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36
Dry So||d I||||ng
W Cranules pelleLs and LableLs can be fllled lnLo capsules uslng
auLomaLlc fllllng machlnes
W roducLs are prepared ln Lhese forms Lo
modlfy Lhe release raLes of acLlve lngredlenLs
Lo separaLe lncompaLlble componenLs
Lo denslfy a producL Lo achleve Lhe flll welghL ln a speclflc slze of
capsule
W 1he machlnes LhaL can be used Lo flll Lhese producLs can be
- Lhe dlrecL
- lndlrecL caLegorles
37
W 1he dlrecL
Lhe maLerlal ls fed lnLo Lhe body unLll lL ls compleLely full
W 1he lndlrecL
Lhe dose of maLerlal ls measured ln a chamber wlLh a
varlable volume whlch can be ad[usLed Lo glve Lhe
requlred welghL
Machlnes have modlfled dosaLors LhaL elLher use sucLlon
Lo hold Lhe maLerlal ln Lhe Lube durlng Lransfer or are
fllled when Lhey pushed up Lhrough Lhe maLerlal bed
Dry So||d I||||ng
38
W roperLles of LableLs LhaL are fllled lnLo capsules
convex and have dlameLers LhaL enable Lhem Lo be
lnLroduced easlly lnLo Lhe body
W Cranules and pelleLs should be regular ln shape so LhaL Lhey
flow and pack well
W 1helr slze should be relaLed Lo Lhe slze of Lhe capsule
Dry So||d I||||ng
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W 1wo Lypes of llquld fllls
1 -onaqueous soluLlons and suspenslons
2 lormulaLlons LhaL are llquefled only for Lhe fllllng
process by elLher heaL or shear sLress
W Wlll need Lo be sealed afLer fllllng
W 1he dose of maLerlal ls measured uslng volumeLrlc pumps
W 1he unlformlLy of flll ls ln mosL cases beLLer Lhan a powder
fllllng machlne
W lllllng machlnes have been made LhaL can handle maLerlals
wlLh vlscoslLles from 100 cp Lo 20000 cp
L|qu|d I||||ng
60
W edusLlng and/or pollshlng operaLlon are compleLed before
Lhe remalnlng operaLlons of lnspecLlon boLLllng and
labellng
W 1he followlng are Lhe meLhods mosL commonly used
an pollshlng
used Lo Lrap Lhe removed dusL as well as Lo lmparL a
gloss Lo Lhe capsules
CloLh dusLlng
rubbed wlLh a cloLh LhaL may or may noL be
lmpregnaLed wlLh an lnerL oll
8rushlng
capsules are fed under roLaLlng sofL brushes
I|n|sh|ng
61
62
owder formu|at|on
W 1he ma[orlLy of producLs for fllllng lnLo capsules are
formulaLed as powders
W 1hese are Lyplcally mlxLures of Lhe acLlve lngredlenL LogeLher
wlLh a comblnaLlon of dlfferenL Lypes of exclplenLs
ICkMULA1ICN
D||uents whlch glve plugformlng properLles
Lubr|cants whlch reduce powder Lo meLal adheslon
G||dants whlch lmprove flow
Wett|ng agents whlch lmprove waLer peneLraLlon
D|s|ntegrants whlch produce dlsrupLlon of Lhe powder mass
1ypes of exclplenL used ln powderfllled capsules
63
Iormu|at|on for f||||ng propert|es
1here are Lhree maln facLors ln powder formulaLlon
Cood flow (uslng freeflowlng dlluenL and glldanL)
-o adheslon (uslng lubrlcanL)
Coheslon (plugformlng dlluenL)
ICkMULA1ICN
64
8loom sLrengLh of gelaLln
Capsules for lnhalaLlon roducLs
CuallLy conLrol of capsules
63
kead|ng Ass|gnments