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7/23/2019 1.3 Capsules and Effective Encapsulation - Shaikh Chand
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and
Effective Encapsulation
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eaker
Shaikh Chand
. . . ec n ca erv cesACG Associated Capsules Pvt. Ltd.
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Contents :
1. Overview on Two piece capsules
a. Capsule Design
b. Manufacturin Process
4. Encapsulation machines
technology
a. T es of technolo
c. Sizes of Capsulesd. Quality Checks
e. Non conformitiesi. Types of Non conformities
ii. AQL
iii. Typical non conformities
b. Encapsulation troubles &counter measures
c. Most common issues while
encapsulation5. Storage/Handling precautions
for Empty capsules
Continual improvements in
Manufacturing process &
systems/new products
6. Q&A
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CAPSULE SHELLS
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DESIGN OF CAPSULE SHELLDESIGN OF CAPSULE SHELL
Note: This is only illustrative sketch. The design features varies with
supplier and their product range.
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DESIGN OF CAPSULE SHELLDESIGN OF CAPSULE SHELL
Note:
The Pre-Locked and Locked Length may differ for two suppliers,
hence filling machine settings are required to be adjusted as per Capsule
suppliers specifications.
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HARD GELATIN CAPSULES INGREDIENTS
ACG ASSOCIATED CAPSULESACG ASSOCIATED CAPSULES
Gelatin
Water
Colours & Titanium Dioxide Imprinting Ink
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CAPSULE SHELL MANUFACTURINGCAPSULE SHELL MANUFACTURING
1. Gelatin raw material is mixedin DM water at 80 deg centto form a viscous colourless
solution in Melter mixer2. The Clear solution is
dispensed in a smaller feed
tanks. Colourants are addedas per customer approval.
3. Lightnin stirrers used for
bubbles.4. Gelatin Solution is kept for
settling for De- Bubbling.
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Capsule moulding
HCM line clearance
PROCESS FLOWPROCESS FLOW -- MANUFACTURINGMANUFACTURING
Stripping, cutting, joining
Drying
Process & Product control
checks
In-process QC
checks
CompliesDoes not comply
Reject Printing / Packing
Automatic capsule transfer
Moisture stabilisation
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PACKING:
Primary : Food grade multi-layer co-extruded poly bag
2
PACKING, STORAGE AND HANDLINGPACKING, STORAGE AND HANDLING
STORAGE:
Temperature : 150 C to 300 C (590 F to 860 F)
RH : 40% to 65%
TRANSPORTATION :
Road : Temperature controlled A/C vans
Sea : Reefer Containers
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QUALITY SYSTEMQUALITY SYSTEM
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ININ--PROCESS QC CHECKSPROCESS QC CHECKS--MEASURABLEMEASURABLE
Single wall thickness
Outside diameter
Dome thickness
Shoulder thickness
Length
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DEFINITION OFDEFINITION OF
CAPSULE NON CONFORMITIESCAPSULE NON CONFORMITIES
Critical defect
capsule as package for the final product orcontributes to a major filling problem
Major defect Is a defect that may cause a problem on afilling machine
Minor defect
performance of a capsule as a package. Itis a slight blemish that makes the capsulevisually imperfect.
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CATEGORIZATION OFCATEGORIZATION OF
CAPSULE NON CONFORMITIESCAPSULE NON CONFORMITIESCritical defects Major defects Minor defects
Holes Loose ieces Minor s lits
Uncut cap / Body Closed capsules Minor rough cuts
Cracked / Split Double caps Minor collet pinches
Short body Bad join Minor punched dome
Double dip Major rough cuts BubblesTelescoped Major collet pinches Wrinkles
Trims Thin spots SpecksString on end Short cap Dirt marks
Long body StringsLong cap Scrapes / scratches
Grease / Oil rings
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SAMPLING PLAN & AQLSAMPLING PLAN & AQL
Visual defects are evaluated based on sample size & acceptance numberderived from the ISO 2859 Part I using single sampling plan.The AQLs indicated could be verified on a composite random sample drawn from
, .
Categorization
of defects
Lot size 500,000 & above
Sample size*Acceptance
numberRejectionnumber AQL % AOQL%
CAPSULE DEFECTS
r ca . .
Major 1250 1 2 0.04 0.067
Minor 1250 7 8 0.25 0.360
* To be selected from ( k + 1 ) cartons where k = number of cartons in the lot.
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TYPICAL NON CONFORMITIES
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Pin Holes / HolesPin Holes / Holes
-
Definition: Capsule, which has beenpierced on any part of its surface
Causes
o Mechanical touch durin Mould
strippingo Loose/Bend Mould pins
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BubblesBubbles
Definition: Capsule having bubbleeither on cap or body having
diameter more than 1 mm
Causes
o Preparation of Gelatin Solution
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Loose Cap / BodyLoose Cap / Body
Defect Classification - Ma or
Definition: It is a cap or body in un-joinedstate.
Causes
o Two parts not joining on Capsule
o Capsules becoming Loose during postmanufacturing activities
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Metal ParticlesMetal Particles
Causes
o Metal to Metal Friction onmanufacturing machines
o Impurities in Gelatin /Dyes
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Black SpotsBlack Spots
Defect Classification - Minor
Definition: Capsule having
speck/Spots either on cap or bodyhaving diameter more than 1 mm.
Impurities in Gelatin solution/ Dyes
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Cracked/Splits/TelescopedCracked/Splits/Telescoped
Defect Classification - Critical
Definition: Capsule having longitudinal break infilm straight or spiral, from the edge of cap orbody cut end.
Capsule with Cap/Body partially cut duringjoining
Causeso Capsule joining defect (On filling machine or
in Empty capsule)
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ENCAPSULATIONENCAPSULATION
TECHNOLOGYTECHNOLOGY
TYPES OF ENCAPSULATIONTYPES OF ENCAPSULATION
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TYPES OF ENCAPSULATIONTYPES OF ENCAPSULATION
TECHNOLOGYTECHNOLOGY
Capsule FillingMachines
Hand Filling Semi Automatic Automatic
Intermittent Rotary
Dosingprinciple
Tampingprinciple
Dosingprinciple
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ENCAPSULATION TROUBLESENCAPSULATION TROUBLES
AND COUNTERMEASURESAND COUNTERMEASURES
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CAPSULE ORIENTATION LOADING ANDCAPSULE ORIENTATION LOADING AND
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CAPSULE ORIENTATION, LOADING ANDCAPSULE ORIENTATION, LOADING AND
SEPARATIONSEPARATION
capsule separation.
Too high vacuum can cause the Cappart of capsules to pop out afterseparation.
Dome part of Body may come apartdue to high vacuum.
CAPSULE ORIENTATION LOADING ANDCAPSULE ORIENTATION LOADING AND
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When loading into upper bushes/Capsegments, the capsules should not hit to the
CAPSULE ORIENTATION, LOADING ANDCAPSULE ORIENTATION, LOADING AND
SEPARATIONSEPARATIONcontdcontd
e ges.
For correct rectification and loading, adjust thepositioning of capsules in rectification Block by
Horizontal fingers.
Adjust the opening time of vacuum when ittouches the bottom part of Body bushes. Itshould not be delayed time.
UNOPENED CAPSULES REJECTIONUNOPENED CAPSULES REJECTION
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UNOPENED CAPSULES REJECTIONUNOPENED CAPSULES REJECTION
(NON SEPARATION)(NON SEPARATION)
Verify if Non Separated capsules are tight to open whenpu ng apar
Check the vacuum for capsule separation. Get as perrecommendation of Machine supplier
Plug the losses of Vacuum from Vacuum line
Clean the filter bags Verify the alignment of Cap and Body Bushes.
separation and if so correct the machine settings.
UNOPENED CAPSULES REJECTIONUNOPENED CAPSULES REJECTION
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UNOPENED CAPSULES REJECTIONUNOPENED CAPSULES REJECTION
(NON SEPARATION).(NON SEPARATION).contdcontd
or emp y capsu e separa on, e es re vacuum range orAutomatic Filling (AF) machines is 16 to 24 (400 mm to 600mm) of Hg and the Vacuum valve should be operative withcorrect timing.
For Multi Ejector pump, (operated on Compressed Air) Vacuumpressure should be between 0.2 to 0.3 bar and Inlet Air should
e g q. cm
CAPSULE CLOSING (SPLITS/DENTS)CAPSULE CLOSING (SPLITS/DENTS)
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CAPSULE CLOSING (SPLITS/DENTS)CAPSULE CLOSING (SPLITS/DENTS)
Common Causes of Denting
1. Capsules are closed to lower than.
2. Cap and Body segments are notaligned. (Use alignment pins for verification and correction)
3. Closing pins are not in the center of bushes.
4. Flat Closing Pins Concave is better5. Overfilling
CAPSULE CLOSING (SPLITS/DENTS)CAPSULE CLOSING (SPLITS/DENTS)
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CAPSULE CLOSING (SPLITS/DENTS)CAPSULE CLOSING (SPLITS/DENTS)
Common Causes of Splits/Telescopes
1. Excessive gap or No gap between Cap
dome of capsule and closing plate orTop pin2. Abrasive Powder/No slug Formation3. Closing pins are not in the center of
bushes.4. Cap and Body segments are not
aligned. (Use alignment pins forverification and correction
5. Misalignments during running of themachine due to wearing of machineparts / loose fitted parts
CAPSULE CLOSING (SPLITS/DENTS)CAPSULE CLOSING (SPLITS/DENTS) tdtd
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Enlar ed internal sizes of se ments
CAPSULE CLOSING (SPLITS/DENTS).CAPSULE CLOSING (SPLITS/DENTS).contdcontd
or Bushes can cause Splits/ Foldingor breaking in filled capsules.
Assessment of Wear and Tear is
recommended
PRECAUTIONS ON AUTOMATIC FILLINGPRECAUTIONS ON AUTOMATIC FILLING
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PRECAUTIONS ON AUTOMATIC FILLINGPRECAUTIONS ON AUTOMATIC FILLING
MACHINESMACHINES
Filled Capsule Ejection :
See that the ejection issmooth.
Cap denting or damaging isgenerally seen whenalignment is not proper or
capsule.
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SERVICESSERVICES
YOUR GLOBAL PARTENER IN SOLID DOSAGE SYSTEMS
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SERVICE INFRASTRUCTURESERVICE INFRASTRUCTURE
Sales and Customer Service
Technical Service Regulatory Support
Product Development
YOUR GLOBAL PARTENER IN SOLID DOSAGE SYSTEMS
REGULATORY SERVICEREGULATORY SERVICE
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REGULATORY SERVICEREGULATORY SERVICE
Support offered :
Documentation
Queries
Color shade development center
Access Letters Empty Hard Capsules
Printing Ink Dedicated Regulatory Cell for ANDA business
TECHNICAL SERVICETECHNICAL SERVICE
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TECHNICAL SERVICETECHNICAL SERVICE
Experts in capsule machine interface
Pro-active visits to customers
Enable customers to improve productivity
Training on encapsulation machines on shop
floor
Develo ment of customized solutions
Support on scalability & interchangeability offilling machines
APPLICATION DEVELOPMENT LABAPPLICATION DEVELOPMENT LAB
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Facility at Mumbai -
APPLICATION DEVELOPMENT LABAPPLICATION DEVELOPMENT LAB
75 % RH Simulated studies are performed Studies on Color Compatibility Multi-media dissolution studies Dissolution & tabilit studies on new
capsules product Liquid in Hard Gelatin and HPMC capsule
trials
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CAPSULE SHELL HANDLINGCAPSULE SHELL HANDLING
PRECAUTIONSPRECAUTIONS
HANDLING PRECAUTIONSHANDLING PRECAUTIONS
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Avoid damages to Empty capsules while transfer and handling.
a e e ags or con a ners con a n ng capsu es proper y so athere is trace ability of batch/vendor.
Maintain Capsule filling conditions for temperature 20 C to 25 C
and 45 % to 55 % RH.
Issue / take capsule boxes preferably in sequence or nearby box. , , , . , , ,
HANDLING PRECAUTIONSHANDLING PRECAUTIONS
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Always seal the capsule bags airtight after sampling & dispensing.
Keep the capsules containing boxes away from the adjacent wallsand also from the ceiling.
Use only S. S. scoops & spatulas having smooth, blunt and
rounded edges. Plastic material develops Static charge on use.
HANDLING PRECAUTIONSHANDLING PRECAUTIONS
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Even for brief period, do not store the capsules near a source of
heat.
Avoid wide temperature fluctuations during storage and handling.
HANDLING PRECAUTIONSHANDLING PRECAUTIONS
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Do not leave the capsules in hopper of capsule filling machine.
Colour fading can also occur if the capsules contain lightsensitive dyes are exposed to light for longer time.
Dont use plastic scoops /containers for capsule transfer orcollection as they develop static charge.
SummarySummary
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yy
Prevent leakages of vacuum from Vacuum lines upto theseparation point of empty capsules.
.(Generally provided by Machine supplier)
For Hygroscopic and sticky powders, clean the bushes
and machine parts at frequent intervals. Clean the filter bags at regular frequency.
Finer adjustments on machine settings can result intoeliminating chances of variations in performance fromBatch to batch.
FILLING MACHINES COMPARISON :FILLING MACHINES COMPARISON :
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SPEED VS OUTPUTSPEED VS OUTPUT
The high output machine may not necessarily be thehigh-speed machine.
More no. of strokes per minute means lesser contact timefor capsules to open and close. Hence, machine settingsbecome more critical and essential for such machines.
Proper vacuum is essential particularly for High Speedand High out put machines.
( Get and maintain as per machine manufacturersspecification.)
FILLING MACHINES COMPARISON :FILLING MACHINES COMPARISON :
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6 x 1= 61PAM - AF40 T
Theoretical output/
HourStrokes/Min
No. of capsules for
each stroke
Loading
stationsMachine Type
SPEED VS OUTPUTSPEED VS OUTPUT
=-
40,0001355 X 1 = 51Bosch - GKF 700 S
135,0001408 x 2 = 162Seejong - 135
100,0001207 x 2 = 142Seejong - SF100
70,000986 x 2 = 122Seejong - SF70
150,0001409 x 2 = 182PAM - AF150 T
90,0001087 x 2 = 142PAM - AF90 T
,
150,0001359 x 2 = 182Bosch-GKF 2000
200,00013513 x 2 = 262Pam - AF 200 T
84,0001405 x 2 = 102Bosch - GKF 140040,0001126 x 1 = 61IMA -Zanazi 40 F
,
Empty gelatin capsulesEmpty gelatin capsules
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Widest possible range of sizes
available :
p y g pp y g p
Sizes : # 000 (Biggest)
#00, # 0, # 1, # 2, # 3, # 4 &
# 5 (Smallest)
S ecial sizes - # 00EL # 0XEL # 0EL
# 0EL+, # 1EL, # 2 EL
Shades : Over 5000
ACG Capsule sizes
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ACG Capsule sizes
HPMC capsulesHPMC capsules
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NATURE CAPS
Low moisture capsules
Specially designed for high -
speed automatic machines
FLOFITFLOFIT
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Capsules forCapsules for Liquid filling
AN ALTERNATIVEAN ALTERNATIVETO SOFT GEL CAPSULESTO SOFT GEL CAPSULES
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TO SOFT GEL CAPSULESTO SOFT GEL CAPSULES
Liquid filling in hard gelatin & HPMC capsules & band sealing of capsules
u oma c an ea ng ac ne
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INNOVATIONINNOVATIONNew product offerings
CLINICAPS
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CLINICAPS capsules allows blinding of- -
or other capsules.
Simply fill the capsules manually, or on
conventional filling machines
, , ,
Shorter length facilitates ease ofswallowing
MARINECAPS (Fish Gelatin Capsules)MARINECAPS (Fish Gelatin Capsules)
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Being non-ruminant material, it does not pose the risk ofBSE/TSE.
Not a suspect material for BSE/TSE under regulation EQN999/2001& further amendments to EuropeanPharmacopia.
Low water vapor transmission rate.
Low oxygen permeability.
TD Caps : Capsules for Dry Powder
I h l ti ( DPI )
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Inhalation ( DPI )Regular capsules DPI capsules
Product requirement :
- Low powder retention- Clear capsules after dosing- Capsule retention shall be less than 5%- DOED shall be not less than 25% by TSLI method- Non reactive lubricant
DOED deposition of emitted doseTSLI - Twin stage liquid impinger
SPECIAL SIZES OF CAPSULES
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Gelatin capsules- available in special sizes, namely
size # 000 00el 0Xel 1el 2el 5
Customized sizes of capsules can be made available
as a joint development project
PEARLZ CAPSULES
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PearlzPearlz ca sules ca sules -- with awith a
unique shine to give yourunique shine to give yourbrand stand outbrand stand out
Available in HPMC & GelatinAvailable in HPMC & Gelatincapsulescapsules
PROMOTINGPROMOTING
ANTIANTI--COUNTERFEIT MEASURESCOUNTERFEIT MEASURES
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ANTIANTI--COUNTERFEIT MEASURESCOUNTERFEIT MEASURES
Oriented Circular Printing 2 Color Print on capsules 360 degree printing
PROMOTINGPROMOTING
ANTIANTI--COUNTERFEIT MEASURESCOUNTERFEIT MEASURES
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ANTIANTI--COUNTERFEIT MEASURESCOUNTERFEIT MEASURES
First Time GLOBALLYFirst Time GLOBALLY
Brand Shield 4 C (4 Color Printing)
REGULATORY MARKET SUCCESS
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More than 100 capsule molecules underqualification process with 50 generic
manu acturers
Partnering with 4 of the top 5 Global generic
companies
Strategic supplier for MNCs for Site transferproducts in India
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THANK YOU