PREPARED BY:

MASI MD.INAYAT A.
M.PHARM:1
ROLL NO:06
GUIDE BY:
DR. M.M.SONIWALA
DEPT. OF PHARMACEUTICS
B.K.MODY GOVT. PHARMACY COLLEGE,RA1KOT
NTRODUCTON
ADVANTAGE & D8ADVANTAGE
PLANT LAYOUT
MANUFACTURNG PROCE88
EOUPMENT8
8TANDARD OPERATNG PROCEDURE
VALDATON PROTOCOL
.P.O.C
FNAL PRODUCT O.C
BMR
BPR
NOVEL N 8OFT CAP8ULE
C(7/;V1 .
Capsules are unlL solld dosage forms ln whlch Lhe drug subsLance ls
enclosed ln elLher a hard or sofL soluble conLalner or shell of a sulLable
form of gelaLln"
sofL capsules have shells conslsLlng of slngle cyllndrlcal roundoval
secLlons
A sofL gel (a sofL gelaLln capsule) ls a unlL solld capsule (ouLer shell)
surroundlng a llquld or semlsolld cenLer (lnner flll) An acLlve lngredlenL
can be lncorporaLed lnLo Lhe ouLer shell Lhe lnner flll or boLh
AL Anu L Cl Cl1
CADL
pherlcal(round) 003 3 ml
Cvold(oval) 003 7 ml
Cyllndrlcal(oblong) 013 23 ml
1ubes 03 0 ml
ear shaped(mlsc) 03 3ml
mproved bloavallablllLy
mproved conLenL unlformlLy of lowdose acLlve subsLances
Lnhanced sLablllLy
1hey are mosL sulLable for llqulds and semlsollds and are wldely used
8educed dusL for handllng poLenL compounds
Mlnlmlzed gasLrlc lrrlLaLlon
usLalned release
Lase of use easy Lo swallow no LasLe unlL dose dellvery
versaLlle
l AccommodaLes a wlde varleLy of compounds fllled as a
semlsolld llquld gel or pasLe
ll Wlde varleLy of colors shapes and slzes
lll mmedlaLe or delayed drug dellverycan be used Lo lmprove
bloavallablllLy by dellverlng drug ln soluLlon or oLher absorpLlon
enhanclng medla
AuvAn1ACL
uAuvAn1ACL
> WaLer soluble maLerlal are dlfflculL Lo lncorporaLe
> lghly MolsLure senslLlve
> LfflorescenL maLerlal cannoL be flll Lhey may cause sofLenlng
> uellquescenL maLerlals cannoL be lncorporaLed Lhey may
cause hardenlng or brlLLle capsules
Lx Cl nnL8 l MA1L8A
1) neaL ubsLance especlally olly llqulds
eg Cod llver oll capsules
2) oluLlon lllls AcLlve dlssolved ln a carrler
eg Clls such as soybean oll and Mlglyol 812 (neuLral oll Lrlglycerldes of
medlum chaln faLLy aclds)
eg olyeLhylene Clycols especlally LC 400 600
eg CLher solvenLs Any oLher solvenL whlch does noL degrade or
solublllze Lhe gelaLln shell le dlmeLhyl lsosorblde surfacLanLs
dleLhylene glycol monoeLhly eLher
3)CpLlonal ngredlenLs for soluLlon fllls
1 WaLer or alcohol up Lo 10 w/w (lf needed for solublllLy)
2 Clycerln 1 Lo 4 w/w (Lo reLard Lhe mlgraLlon of Lhe glycerln ouL of
Lhe shell lnLo Lhe flll)
3 olyvlnylpyrrolldone Dp Lo 10 w/w used ln comblnaLlon
wlLh LC (can lncrease drug solublllLy and also lmprove
sLablllLy by lnhlblLlng drug recrysLalllzaLlon)
4 uspenslon lllls AcLlve dlspersed ln a carrler
uspenslons can accommodaLe abouL 30 sollds before
vlscoslLy and fllllng become a problem
uspenslons can be heaLed up Lo 33C Lo decrease vlscoslLy
durlng Lhe fllllng process
uspended sollds musL be smaller Lhan 80 mesh mlll or
homogenlze before fllllng Lo prevenL needles from clogglng
durlng fllllng
CHANGE
ROOM{F_
CHANGE
ROOM{M_
OFFCE
D8PEN8NG
MAT.
8TORE
CC88uC8L
UNCLEANED
CONTANER
DRYNG
OFFCE
8PARE
8PART8
PACKAGNG
AREA
BL8TER
PACKNG
FLL
CAP8ULE
8TORE
ROOM
A

R


L
O
C
K
A

R


L
O
C
K
.P.O.C
NTERMDATE
8TORE
GELATN
PREPARATON
MEDCAMENT
PREPARATON
ENCAP8ULATON
AREA
WA8HNG
ROOM
8OLVENT
8TORE
ROOM
1wo f|oor bu||d|ng f|rst
preparat|on of med|cament
and ge|at|n encapsu|at|on
room at ground f|oor
Requirements in manufacturing area : schedule M 23 M
2
+ 10 M
2
ancllla
Air-conditioned Temperature-20-220C
Humidity Operating areas-40%
Drying areas-20-30%
COTO5JJO O 5O C.T5'11 5111
1) 1) GLLA1IN Ck GLLA1IN Ck
NCN GLLA1IN NCN GLLA1IN
lanL derlved hydrocollolds
ynLheLlc olymer %%apter 11 - Iormu|at|on and ps|ca| propert|es of soft capsu|es 8 Cobtlele kelcb pp 204)
2) WA1Lk 2) WA1Lk N.M.T 45W/W N.M.T 45W/W
) LAS1II2Lk GLLkIN ) LAS1II2Lk GLLkIN
SCk8I1CL SCk8I1CL
4) kLSLkVA1IVLS ML1nL AkA8LN 4) kLSLkVA1IVLS ML1nL AkA8LN
kCL AkA8LN kCL AkA8LN
S) CLCkAN1S ID Lk1IIILD LAkLS S) CLCkAN1S ID Lk1IIILD LAkLS
6) CAIIILk 1I1ANIUM DICkIDL 6) CAIIILk 1I1ANIUM DICkIDL
7) ILAVCUkING AGLN1 L1nL VANILLIN 7) ILAVCUkING AGLN1 L1nL VANILLIN
8) AN1I 1ANNING AGLN1 IUMAkI AID %AIDS 1C SCLU8ILI1) 8) AN1I 1ANNING AGLN1 IUMAkI AID %AIDS 1C SCLU8ILI1)
9)SUkIA1AN1 01S w]w SLS 9)SUkIA1AN1 01S w]w SLS
10)nLLA1ING AGLN1S Na LD1A 10)nLLA1ING AGLN1S Na LD1A

S1LS CI MANUIA1UkING CI SCI1 GLLA1IN ASULL SnLLL
EQUIPMENTS
ENCAPSULATION MACHINE :
TUMBLER DRYER
TUNNEL DRYER
GELATIN SERVICE TANKS
MEDICAMENT PREPARATION EQUIPMENT
MEDICINE SERVICE TANKS
AUTO SORTER
PACKAGING LINES :
FLAT BED BLISTER PACKAGING MACHINE, MAKE ELMACH.
ALU ALU PACKAGING MACHINE.
BOTTLE FILLING MACHINE.
1/17;V
,^^
J1J7;CV
CC,
L8T OF METHOD8
1) HAND DIPPING METHOD
2) GLOBEX METHOD OR LAML CLA1n CADL
3) ROTORY DIE METHOD
4) ACCOGEL METHOD
5) NORTON METHOD
6) COLTON METHOD
7) UPJOHN METHOD
8) PLATE METHOD
9) RECIPROCATING DIE METHOD
Immed|ate| after manufacture capsu|es are sub[ected to
#ff# was to remove m|nera| o|| form te outer
surface of te capsu|e
entr|fuge |s used for capsu|e was|ng
roducts are presaped sem| dr|ed |n tumb|er
waser dr|er un|ts
1umb|er dr|er un|t av|ng
temp S
0
w|c removes
A|| te so|vent used |n was|ng
and S0 60 of water
ASULL DkING 1UNNLL SS1LM |s constructed from modu|ar
pane|s |n sta|n|ess stee| AISI 04
1e tunne|s ave a |am|nar f|ow a|r f||trat|on un|t w|c a||ows a
better and more eff|c|ent dr|ng of te capsu|e products
100 |nspect|on |s performed on te externa| appearance %Improper
Sea||ng o|or Soft spot Seam cont|nu|t)
apsu|es are manua|| |nspected for ps|ca| defects
Cn||ne Automat|c apsu|e Inspect|on Mac|ne
Affordab|e
camera sstem
120000 apsu|es]ours
INSLAS 1S0
apsu|es are overpr|nted for |ogos or trade marks |f requ|red
roducts are str|p packed b||ster packed bott|e pack and bu|k
packed as requ|red
STANDARED OPERATING PROCEDURE
PREPARATION OF GELETINE MASS
CelaLln D grade
8loom or Cel sLrengLh130230 g
vlscoslLy2343 mllll polse
ronnM1 13 ppm
Mlcroblal conLenLnM1 1000 organlsms/gram
1oLal absence of almonella and Lcoll
TOTAL CUONTS OF
ORGANISUM
1000 /GRAM
E .COLI NIL
SALMONELLA NIL
SHAPES CAPESITY(ML)
SPHERICAL 0.05 -5 ML
OVOID 0.05 -7ML
CYLINDRICAL 0.15 -25 ML
TUBE 0.5 10 ML
PEAR SHAPED 0.3 -5 ML
I.P. 1996 for empty SGC Shell.
GENERAL REQUIREMENT:
Environment condition
The area around machine should be kept clean at all times.
The speed gear should not be adjusted when the machine is running on
power,
Area 1emp umldlLy
CuaranLlne area 2224
0
C 43
8aw maLerlal sLorage 2224
0
C 43
llll maLerlal preparaLlon 2224
0
C 33
LncapsulaLlon 2224
0
C 1320
urylng 2224
0
C 1320
nspecLlon 2224
0
C 33
ackaglng 2224
0
C 33
llnlshed producL 2224
0
C 33
PRELIMINARY OPERATIONS
The RH in the room or area should be checked and recorded on
manuIacturing sheet.
Filling should not be started iI humidity is more than 50
LOADINGAND RECTIFICATION
Rotary die machine check the rotation speed &contact time .
And load the gelatin mass & medicament in hopper & Iorm capsule.
CLEANING OF MACHINARIE
External surIace Use a clean nylon brush and vacuum cleaner.
CLEANING OF PARTS - clean the above parts by washing with
0.1Teepol solution and scrubbing with soft clean nylon brush.
CLEANING OF CAPSULE PLATES- capsule plates are soaked in
hot 5 micron filtered water for 5-10min. The holes are cleaned using
0.1 Teepol solution.
CLEANING OF MACHINE BODY- clean with 0.1 Teepol solution
and scrubbing with soft nylon brush. Clean with potable water.
Drying - after washing all part are dry .
Assembling -carefully checking assembling and free motion of
moving parts.
Equipment Parameter
Rotary die machine Die rotation speed controls &
contact time
Tumbler drier Temp. 35
0
C
Tunnels drier Laminar Ilow air Iiltration unit(
better and more eIIicient drying oI
the capsule products)
Sea| t|ckness and r|bbon t|ckness
Un|form|t of mass
I||| matr|x we|gt
apsu|e se|| we|gt
Mo|sture content soft ge| ardness at te end of
te dr|ng stage
During encupsuIution
Sea| t|ckness and r|bbon t|ckness
Un|form|t of mass
D|s|ntegrat|on t|me
I||| matr|x we|gt
1emp of ge|at|n tank
apsu|e se|| we|gt
Mo|sture content soft ge| ardness at te end of
te dr|ng stage
PHARMACOPIEAL STANDRAD
A1IVL INGkLDILN1 ASSA
kLLA1LD INGkLDILN1 ASSA
UNIICkMI1 CI MASS
UNIICkMI1 CI CN1LN1
DISSCLU1ICN 1LS1
MIkC8IAL 1LS1
MCIS1UkL CN1LN1 DL1LkMINA1ICN
kU1UkL 1LS1
INDUSTRIAL STANDRAD
DIMLNSICN
ASULL SnAL
SCLU8ILI1
CDCUk
M/s (name and address of company)
_____________________________________________________________________________________________
_____________________________________________________________________________________________
name of producL _______________________________________________________________________________
(1rade name lf any)______________________________________________________________________________
(Ml8no) ______________________________________________________________________________________
8aLch no ________________________________________ Capsule slze ___________________________________
8aLch slze ___________________________________________ Colour _________________________________
uaLe of Lxplry _____________________________________________________________
uaLe of commencemenL ____________________________________________________

AcLual welghL of blended powder

______________________________
1heoreLlcal welghL of blended powder
__________________________
WheLher wlLhln llmlLs
______________________________________
__
F
Average welghL of capsules ___________________________________
Average welghL per capsule ___________________________________
ermlsslble welghL varlaLlon llmlL _______________________________
uaLe and Llme pollshlng commenced______________________________
uaLe and Llme pollshlng sLopped _________________________________
8esulL of LesLlng/analysls of
bulk flnlshed producL __________________________________________
(LaLus 8ecelpL no uaLe)
____________________________________________________________________________
DkING
1nlLlal wL of capsule
2AfLer drylng wL of capsule
ackaglng descrlpLlon______________________________
recodlng of labels and prlnLed packaglng maLerlals examlned
(aLLach speclmen)
verlfled by_______________________________
no of recoded abels recelved___________________________________
rlnLed packaglng maLerlal recelved___________________
1oLal CuanLlLy packed______________________________________
uaLe of compleLlon________________________________________
CLy collecLed as samples by C/C ueparLmenL___________________
Recunciliatiun uf labelling & Packaging aterials
AcLual yleld ____________________________________________________
1heoreLlcal yleld ________________________________________________
WheLher wlLhln llmlLs _____________________________________________
C/C 8eporL of flnlshed producL _____________________________________
LaLus no daLe and release order) ________________________________
lgn of upervlsor
(approved Lechnlcal sLaff)
uaLe of release _________________________________________________
CLy released ___________________________________________________
uaLe of Lransfer of flnlshed ________________________________________
roducL Lo warehouse _____________________________________________
CounLer slgned _________________________
LAu Cl CDA1? CCn18C uLA81MLn1
`C`li l` C1 "(il
8LCLn1 DuA1L n CADL
1LCnCCC?
A) new producLs by Capsugel
1 Capsugel has lnLroduced Cceancaps capsules
2 lcaps all slzeshape capsules are ldeal for maxlmlzlng llquld
dosage wlLh a flll capaclLy of 1000mg Lo 1400mg dependlng
on Lhe denslLy of Lhe llquld flll maLerlal
new producL by naLco harma
DA18L1 a medlclne used ln Lhe LreaLmenL of a rare form of
leukemla
BOOKS
Pharmaceutical Process Validation by LOFTUS and NASH PP 298
Leon Lachman, Herbert A. Lieberman, Joseph L. Kanig ,The theory and
practice oI industrial pharmacy , Third edition ,Varghese publishing
house, 1991, pp 681-703.
Graham cole, Pharmaceutical production Iacilities design and
application, second edition, Taylor and Irancis e-library, 2003, pp 175-
196.
Formulation and physical properties oI soIt capsules by Gabriele Reich,
Pharmaceutical Technology Capsules Dr. Bhawna Bhatt ,ProI. S.S.
Agrawal
ARTICLE
Habiba I. Benza, and Were L.L. Munyendo, A review oI progress and
challenges in soIt gelatin capsules Iormulations
For oral administration, Volume 10, Issue 1, September October 2011;
Article-004International Journal oI Pharmaceutical Sciences Review and
Research
Margareth R.C. Marques,ab Ewart Cole,c Dale Kruep,d Vivian Gray,e
Dennis Murachanian,I William E. Brown,a Gabriel I. Giancasproa,
Liquid-Iilled Gelatin Capsules Pharmacopeial Forum Stimuli articles do
not necessarily reIlect the policies Vol. 35(4) |JulyAug. 2009|
Oral lipid based Iormulation: a review,www.ijpbs.net
Biopharmaceutics M. Nagaraju patro, ajit s. Bankar, sachin ,uttam
rakesh, dr. A. V. Yadav, International Journal oI Pharma and Bio Sciences
V1(2)2010
Available Online through Review Article,A review on capsules in
pharmacy,M.Karteek1*, K. Bala Krishna, ISSN: 0975-766X,CODEN:
IJPTFI
WEBSITE
www.eravat.com
www.safrroy.com
www.made-in-china.com
www.indianindustry.com
www.fujicapsule.com/english/system/seam.htm
http://pharmlabs.unc.edu/capsules/text.htm
www.pharmagel.it/production2.htm
www.drugdeliverytech.com
www.capsugel.com
www.innercaps.com
www.intota.com/viewbio.