The document discusses process validation for oral solid dosage forms like tablets. It defines process validation and the different types - prospective, retrospective, and concurrent validation. It provides details on validation protocols, including general information, objectives, process flow charts, critical parameters, and acceptance criteria. Key processing steps for tablets are also summarized, like mixing, wet granulation, milling and factors that influence them like material properties, equipment used, and processing parameters. The goal of process validation is to ensure consistent production of tablets meeting quality standards.

1. PROCESS VALIDATION OF ORAL
SOLID DOSAGE FORM (TABLET)
Submitted to:- Prepared by :-
Dr. Sanjula Baboota Abdul Muheem
M.Pharm 1st Year
F/O Pharmacy
(Pharmaceutics)
Jamia Hamdard JAMIA HAMDARD
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2. DEFINITION
• US Food and Drug Administration, 1987
“Process Validation is establishing documented
evidence which provides a high degree of assurance
that a specified process will consistently produce a
product meeting its pre-determined specifications
and quality characteristics.”
 is the documented evidence that the process,
operated within established parameters, can
perform effectively and reproducibly to produce an
intermediate or API meeting pre-determined
specifications and quality attributes.”
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3. Types of process validation
PROCESS
VALIDATION
RETROSPECTIVE CONCRURRENT
PROCESS PROCESS
VALIDATION VALIDATION
PROSPECTIVE
PROCESS
VALIDATION
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4. DEFINITIONS
 PROSPECTIVE PROCESS VALIDATION
Prospective process validation shall be carried out before
the Process is commercialization. Minimum 3 consecutive
batches to be considered. The important requirement for
the validation is protocol preparation.
 RETROSPECTIVE PROCESS VALIDATION
“The retrospective process validation is an established
documented evidence that a process what it purports to do
Based on review and analysis of Historical data.”
 CONCURRENT VALIDATION
“Established documented evidence that a process does what
it purports to do based on information generated during
actual implementation of the process”
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5. Validation Protocol
• 1. General information
• 2. Objective
• 3. Background/Prevalidation Activities Summary of development
and tech transfer (from R&D or another site) activities to justify in-
process testing and controls; any previous validations.
• 4. List of equipment and their qualification status
• 5. Facilities qualification
• 6. Process flow chart
• 7. Manufacturing procedure narrative
• 8. List of critical processing parameters and critical excipients
• 9. Sampling, tests and specifications
• 10. Acceptance criteria
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6. Qualification And Process Validation
Design or Development of Equipment, System, or Product
Installation Qualification
Operational Qualification
Process Performance Qualification
or Process Validation
Change Control
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7. Validation Process flow chart
Pre-Validation Activities
Validation Protocol – Preparation
Validation Protocol- Review and Approval
Protocol Execution
Data Analysis
Validation Report and Sign-Off
Revalidation
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8. Some Common Variables In The
Manufacture Of Tablet Products
 Particle size of drug substance
 Bulk density of drug substance/excipients
 Powder load in granulator
 Amount and concentration of binder
 Mixer speed and mixing times
 Granulation moisture content
 Milling conditions
 Lubricant blending times
 Tablet hardness
 Coating solution spray rate
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9. Validation protocol for manufacturing of tablets
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10. Industrial Process overview of Solid dosage
form
•Steps & process parameter are following-
(1)Mixing or Blending-Material have similar physical
properties will be easier to form a uniform mix or
blend as compare to difference properties.
Techniques-1-diffusion(tumble)
2-convection(planetary or high intensity
or fluid bed.
Mixing or blending depending on various factor-
(a)Mixing speed-mixing the drug & excipient will
require more intense mixing than adding the
lubricant to the final blend.
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11. (b)Mixing time-mixing time will be dependent on
the mixing technique & speed.
• If overmixed occured at the result demixing or segregation
of the material.
(c)Drug uniformity- handling of the material are key in
obtaining valid content uniformity results .
• Segregation of the sample can occur by handling resulting
inaccurate results.
• Sample should be equivalent to the weight of a single
tablet.
(d)Excipient uniformity-excipient need to be uniform in
the granulation.Two keys excipient are-
(A)-LUBRICANT- lubricant needs to be distributed
uniformly in the mixture/granulation for high speed
compression operation .
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12. • Uneven distribution of the lubricant can result in picking &
sticking problem during compresion.
(B)Color-evenly distributed in the mixture so the tablets
have a uniform appreance (color,hue & intensity)
• Uniform dispersed in the blend prior to compression to
avoid shading(molting).
(e)Equipment capacity/load-the bulk density of
material will affect the capacity of the equipment .
• Undercharging or overcharging a blender can result in
poor drug or tablet lubricant distribution.
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13. (2)Wet granulation- what type of wet granulation
technique will be used?
• Will it be of- low shear (hobart)
- high shear rate (diosna )or fluid bed (glatt)
• Wet granulation parameters to be processing during
development &validation are-
(a)Binder addition-should be added as a granulating solution
or dry like other excipients.
• Adding the binder dry avoids the need to determine the
optimal binder conc.
(b)Binder conc.- if the binder conc. are high they are not
ejected by spray nozzle then the binder needs to be dilute
enough so that it can be pumped through the spray
nozzle.
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14. (c)Amount of binder solution /granulating solvent-too much
binder or solvent solution will over wet the material
&prolong the drying time.
• Amount of binder solution is related to the binder conc.
(d)Mixing time—
(e)Granulation end point –how is the granulation end point
determined? is it determined by granulation end point
equipment(eg-ammeter or wattmeter)
(3)wet milling does the wet granulation need to be
milled to break up the lumps & enhance drying of the
granulation
FACTORS-(a)Equipment size & capacity-mill should be
enough large to delump the entire batch within a
resonable time period to min.manufacturing time.
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15. Process Validation of oral solid dosage
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16. (b)Screen size screen needs to be small enough to delump
the material but not too small to cause excesssive heating
of the mill at the result drying of granulation occurred.
(c)Mill speedsufficient speed without causing staining the
equipment.
(d)Feed rateof the wet granulation is interelated to screen
size ,mill size & speed
(4)Drying type of drying technique
(a)tray dryer
(b)fluid bed
(c) microwave
Changing dryer techniques could affect such tablet
properties such as hardness, disintegration ,dissolution &
stability
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17. • High moisture content can result in-
(1)Tablet picking or sticking to tablet punch surfaces
2)Poor chemical properties as a result of hydrolysis .
• An over dried granulation could result in poor hardness
&fraibility.
Moisture content are analysed by following method –
(1)near I.R
(2)loss of drying
(3)karl fischer
FACTORS-(A)Inlet/outlet temp.The inlet temp. is the
temp.of the incoming air to dryer ,while the outlet temp.is
the temp.leaving the unit.
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18. • Inlet temp.should be set high enough to maximinise
drying without affecting the physical/chemical stability.
• The outlet temp.is an indicator is an of the granulation
temp.&will increase toward the inlet temp.as the moisture
content of the granulation decreases (evaporization rate).
(B)Air flowinsufficient air flow could prolong drying
&affect the chemical stability.
(C)Moisture uniformitymoisture content could vary within
the granulation
• Drying is also affect the moisture in the granulation.
(D)Equipment capability/capacity
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19. Process Validation of oral solid dosage
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20. (5)Milling milling operation will reduce the particle size
of the dried granulation.
• An optimal particle size/size distribution for the
formulation will need to determined .
FACTORS-
(a)Mill typewhat mill type should be used(impact or
screen)?
(b)Screen sizeA smaller screen size will produce a small
particle size & a greater number of fines.
(c)Mill speedwhat is the optimal mill speed?
• Higher speed will result in a smaller particle size &
possilbly a wider particle size distribution.
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21. (D)Feed rateis dependent on the mill capacity ,screen
size,mill speed
(6)Lubrication
(a) Selection of lubricantwhat kind of lubricant should be
used?
• Grade of lubricant used
• Compatibility with other ingredient.
(b)Amount of lubricanthow much amount lubricant is
required?
• Too much lubricant will form hyrophobic layer on the
tablet resulting dissolution problem.
(c)Mixing timehow much should the material is mixed to
ensure proper formation?
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22. • Should mixing stop after the addition of the lubricant or
should additional mixing be required ?
• If not mixed long enough from problems like chipping
,capping etc.
(7)Tablet compressionthe material should readily flow
from the hopper onto the feed frame & into the dies.
• Inadequate flow can result in ‘RAT HOLING’in the
hopper.this can cause tablet weight &uniformity problem.
FACTORS(A)TollingThe size ,shape &concavity of the
tooling should be examined based formulation properties
&commercial specification.
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23. (B)Compression speedrange of compression speed to
determine the operating range of the compressor.
• The adequacy of the material’sflow into the dies will be
determined by examining the tablet weights.
• Is a force feeder required to ensure that sufficient material
feed into the dies.
(C)Compression or ejection forcedetermined optimal
compression force to obtain the desired tablet hardness.
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24. • The following in-process tests should be examined during
the compression stage
• Appearance
• Hardness
• Tablet weight
• Friability
• Disintegration
• Weight uniformity
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25. Process Validation of oral solid dosage
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26. • In process tests-
1. Moisture content of dried granulation
2. Granulation particle size distribution
3. Blend uniformity
4. Individual tablet/capsule weight
5. Tablet hardness
6. Tablet thickness
7. Disintegration
8. Impurity profile
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27. (8)Tablet coatingtablet coating can occur by different
techniques(eg-sugar,film or compression)
• Key area to consider for tablet coating include the following-
(a)Tablet properties –the tablet needs to be enough to
withstand the coating process.
• If tablet attrition occurs ,the tablets will have rough surface
appearance
• Round shape easily coated than multiple sides.
(b) Equipment type- coater will need to be selected.
• Conventional or perforated pan & fluid bed coaters are
potential.
(c)Coater load-what is the acceptance tablet load range of the
equipment?
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28. • Too high load at the result attrition occurred.
(d)Pan speed- what is the optimal pan speed?
• It is interelated to coating parameter such as inlet temp.,spray
rate & flow rate.
(e)Spray guns- number & types of guns should be determined in
order to efficiently coat the tablet.
• Size of spray nozzle properly to ensure even distribution over
the tablet bed & to prevent clogging of the nozzles.
(f)Spray rate- spray rate should be determined .
• Spraying too fast will cause the tablets to become over
wet,resulting in clumping of the tablets & possible dissolution
of the tablet surface.
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29. • Spray too slowly will cause the coating material to prior to
adhesion to the tablets,result in rough & poor coating
efficiency.
(g)Tablet flow-flow of the tablets in the coater should be
examined to ensure proper flow.
• The addition of baffles may be required adequate movement
of the tablet for coating.
(h)inlet/outlet temp &air flow-parameter should be set to
ensure that the atomized coating solution reaches the tablet
surface & then is quickly dried.
(i)Coating solution-the conc. & viscosity of the coating solution
will need to be determined.
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30. • The stability of the coating solution should be investigated to
establish its shelf life.
(j)Coating weight-a min. & max. coating weight should be
established for the tablet
(k)Residual solvent level-if solvents are used for tablet coating
,the residual solvent level will need to be determined.
APPEARANCE TESTING FOR TABLET COATING-
• Cracking or peeling of the tablet
• Intagliation fill-in
• Color uniformity
• Coating efficiency should be determined for the coating
operation
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31. • Finished product tests-
1. Appearance
2. Assay
3. Content uniformity
4. Tablet hardness
5. Tablet friability
6. Impurity profile
7. Dissolution
• Process validation testing is generally done on the first three
batches of product made in production –size equipment.
• Revalidation testing is only done when a significant change
has occured.
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32. Conclusion
• Tablet dosage form validation should be part of a
comprehensive validation program within an industry.
• The multidisciplinary validation team must identified the
product & process characteristics that must be studied &
incorporate specific validation tests to ensure that product
will meet all quality , manufacturing & regulatory
requirements.
• Continous awareness of validation will produce
reproducibility .
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33. THANK
YOU
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