SlideShare a Scribd company logo
1 of 36
 Apparatus
1
 The dissolution testing serves as an important tool for
characterizing the biopharmaceutical quality of a product
at different stages in the life cycle . In early drug
development , in vitro dissolution properties are
supportive for choosing between different
alternative formulation candidates for further development
and for evaluation of active ingredients / drug substances .
 Tablets or capsules taken orally remain one of the most
effective means of treatment available. The effectiveness of
such dosage forms relies on the drug dissolving in the fluids
of the gastrointestinal tract prior to absorption into the
systemic circulation.
 “Dissolution is a standardized method for measuring the
rate of drug release from a dosage form and their
solubilization”
2
 The principle function of the dissolution test may be
summarized as follows:
•Optimization of therapeutic effectiveness during
product development and stability assessment.
•Routine assessment of production quality to ensure
uniformity between production lots.
•Assessment of ‘bioequivalence’, that is to say,production
of the same biological availability from discrete batches of
products from one or different manufacturers.
••Provide process control and quality assuranceProvide process control and quality assurance
•Prediction of ‘in-vivo’ availability, i.e. bioavailability
•To create a dissolution profile
•To asses the batch to batch quality
•It provide pharmaceutical scientist relationship between an in vitro
characteristic of a dosage form, and its in vivo performance.
3
•Nature of drug.
• pH.
• Solubility.
• Dissociation constant.
• Particle size.
• Proper selection of dissolution agent.
• Setting of in process parameters.
• Hardness.
• Thickness.
• Physical parameters of tester.
• Temperature
• Media deaeration
• Medium volume
etc.
4
TESTTEST IPIP BPBP USPUSP
TemperatureTemperature 36.5 to 37.536.5 to 37.5 °C°C 36.5 to 37.536.5 to 37.5 °C°C 3737± 0.5 °C± 0.5 °C
pH of MediumpH of Medium ± 0.05± 0.05 ± 0.05± 0.05 ± 0.05± 0.05
Time forTime for
withdrawalwithdrawal
± 2 %± 2 % -- ± 2 %± 2 %
Distance betweenDistance between
bottom of paddlebottom of paddle
and jarand jar
23 – 27 mm23 – 27 mm 23 – 27 mm23 – 27 mm 2525 ± 2 mm± 2 mm
RPMRPM ± 4 %± 4 % ± 4 %± 4 % ± 4 %± 4 %
5
Disintegration is defined as
that state in which any
residue of the unit , except
fragments of insoluble
coating or capsule shell ,
remaining on the screen of the
test apparatus is a soft mass
having no palpably firm core
Simply it is break down of
dosage in define condition
Dissolution
Dissolution is a standardized
method for measuring the
rate of drug release from a
dosage form .
Dissolution is breakdown as
well as release, solubilization of
drug
Generally performed for API
having less solubility.
Disintegration
6
The impartment apparatus as per USP are:
 Type I ( Basket Apparatus ) : The assembly consist of a vessel with
a hemispherical bottom, which may be covered , made of glass or other
inert , transparent material , a motor , a metallic drive shaft and a
cylindrical basket .
 Type II ( Paddle Apparatus ) : Use the same assembly from apparatus
1 , expect that a paddle formed from a blade and a shaft is used as the
stirring device .
 Apparatus 3 ( Reciprocating Cylinder ) : The assembly consist of a
set of glass reciprocating cylinders , inert fittings , a screen and a motor
and drive assembly to reciprocate cylinders vertically inside the vessels .
 Apparatus 4 ( Flow through Cell ) : The assembly consist of a
reservoir and a pump for the dissolution medium ; a flow through cell
and a water bath
7
 Temperature
 Shaft RPM
 Medium
 Bath Level
 Vessels
 Time
8
 Temperature control in tablet dissolution testing is critical as a
change in temperature has a linear effect on the dissolution rate.
Temperature should be measured with a calibrated
thermometer, either analogue or digital, and should normally be 37°C
 The specified temperature should be measure in each vessel prior
to each run commencing . There is a temptation to only
measure temperature in a few of the vessels and assume that
they are all the same. This may not necessarily be the case as
temperature gradients can occur within a water bath that effect the
speed of equilibration of all the vessels.
 Most dissolution baths display the temperature of the bath itself but
this should not be taken as an indication of the temperature
inside the vessel. Typically it is necessary to run the water bath
0.5°C or so above the required temperature to ensure the correct
temperature inside the vessel . If plastic vessels are used instead
of glass then this may be a greater difference.
9
 The USP limit for stirring is ± 4% of the set speed of the test . This level
of shaft control was set during the early days of equipment
manufacturing where surging motors (this temporarily increased
or decreased the speed) were difficult to control . All modern
equipment can now control the speed to within ± 0.5 rpm so this
problem is rare . However the RPM still needs to be
measured periodically with a suitable tachometer.
 For Immediate release tablets, baskets at 100 RPM and Paddles at 50 or 75
RPM are commonly used.
 The RPM outside 25 and 150 are not appropriate because of inconsistency
of hydrodynamics below 25 rpm and turbulence above 150 rpm
10
 Selection of dissolution medium is based on the discriminatory
capabilities,ruggedness and stability of the analyte in the test medium.
 Key factors are solubility of the drug and solution stability.
 Properties that can affect the dissolution are release
mechanism,disintegration rate presence of solubility enhancers and
other excipients.
 Another requirement for developing a dissolution procedure is to have
sink conditions.
 In some cases surfactants are used like SLS or Polysorbate 80. These
help to enhance the drug solubility.
 Also the medium selection depends upon the location of availability of
the drug, for eg
 For release in stomach it is water or 0.1n HCl
 For release in Intestine it is Buffer pH 6.8
 For release in Pancreas it is buffer containing enzymes
11
 Media degassing is important as dissolved gases can causes
bubbles to form , which may change the result of the test .
 High results can occur when the bubbles adhere to the surface of
the tablet particles, increase their buoyancy, and raise them to a
higher part of the vessel where the media flow is quicker.
 Lower results can occur if the bubbles adhere to the surface of the
basket or the tablet forming a physical barrier between the tablet
and the media.
12
 Helium sparging
 Heating and filtering
 Vacuum degassing
Method
% Reduction
(approximate)
USP 84.9 ± 11%
Filtering only at room
temperature
65 ± 3%
Heating to 45°C 10 ± 14%
Boiling 49 ± 3%
Vacuum degassing 50-90%
13
 A releasing medium is the one that promotes solubilization of the drug
substance from a pharmaceutical dosage form without further
qualification .
 A discriminating medium is the one where the more subtle aspects
of the pharmaceutical dosage form can be differentiated by
observing their individual rates of dissolution . Particle size , crystal form,
salt form , presence of water of hydration, differences in the
manufacturing processes ,and so forth , may all affect the dissolution
performance . The dissolution test should be sensitive to any attribute
that may affect the in vivo performance of the product.
14
 The level of a dissolution bath is often overlooked. It should not be
assumed that the laboratory bench is level . This is one of the
parameters that should be checked on installation and some
dissolution testers have an in-built level checking device.
 Testers which are not level can give erroneous results and the media
rotation is not linear within the vessel.
 Level should be tested front to back as well as side to side . A
calibrated level will provide an accurate measurement of this. If the
bath is moved for any reason then this parameter will need to be re-checked.
15
 Vessel design is something that is often overlooked by the analyst. The
USP allows for a significant variation in the specification of the vessels
with a height of 160-170mm and an ID of 98-106mm. This variation
means that if vessels are changed in the bath then the paddle height
and centering measurements need to be rechecked. If the vessels
are serialized then they should be kept in the same position. As well as
the physical dimensions the vessels should be smooth and
scrupulously clean . Small ridges on the inside of the vessel can
greatly increase the dissolution rate whilst scratches and sticky or
gummy patches can reduce them.
16
17
 Introduction to Sampling : Almost every dissolution test relies on
samples being taken to produce a result and anything which affects the
accuracy of a sample should therefore be avoided. Sampling errors
are very common and are often the cause of erroneous results. The
sampling position is critical but so to is the type of sampling probe used.
 The sampling position is important particularly for tests with baskets
as there is often a concentration profile between the bottom of the
vessels and the stirring element . It is less noticeable with paddles as
the extra agitation provides for a more uniform flow profile. The USP
defines the sampling point as "A zone half way between the top of the media
and top of the paddle or basket not less than 1cm from the vessel
wall". Therefore the sampling position will be different for 500ml and
900ml tests. This can create problems for equipment that uses ‘through
the shaft’ sampling.
18
 "A zone half way between
the top of the media and top
of the paddle or basket not
less than 1 cm from the
vessel wall".
19
20
21
 Where a single time specification is given , the test may be concluded in
a shorter period . If two or more times are specified , specimens are
to be withdrawn only at the stated times, within a tolerance of ± 2 % .
 The duration of test is decided by finding the optimum time required for
reaching the peak plasma concentration
“ Q “ Value :
The quantity , Q , is the amount of dissolved active ingredient
specified in the individual monograph , expressed as a percentage of the
labeled content
22
 After the dissolution is over , combine the equal volumes of
filtered solutions of the six or twelve individual specimens
withdrawn and use this solution as a pooled solution .
StagesStages
NumberNumber
TestedTested
Acceptance CriteriaAcceptance Criteria
S 1S 1 66 Average amount dissolved is not lessAverage amount dissolved is not less
than Q + 10 % .than Q + 10 % .
S 2S 2 66 Average amount dissolved ( S 1 + S 2 ) isAverage amount dissolved ( S 1 + S 2 ) is
equal to or greater than Q + 5 % .equal to or greater than Q + 5 % .
S 3S 3 1212 Average amount dissolved ( S 1 + S 2 + S 3)Average amount dissolved ( S 1 + S 2 + S 3)
is equal to or greater than Q .is equal to or greater than Q .
23
Stage Number TestedNumber Tested Acceptance CriteriaAcceptance Criteria
S 1S 1 66 Each unit not less than Q + 5 % .
S 2S 2 66
Average of 12 units (S 1 + S 2 ) is equal
to or greater than Q , and no unit is less
than Q – 15 % .
S 3S 3 1212
Average of 24 units (S 1 + S 2 + S 3 )
is equal to or greater than Q , not more
than 2 units are less than Q – 15 %,
and no unit is less than Q – 25 % .
24
Stage Number TestedNumber Tested Acceptance CriteriaAcceptance Criteria
A 1A 1 66 No individual value exceed 10%
dissolved.
A 2A 2 66
Average of 12 units (A 1 + A 2 ) is Not
more than 10% dissolved,and no
individual unit is greater than 25%
dissolved.
A 3A 3 1212
Average of 24 units (A 1 + A 2 +A3 ) is
Not more than 10% dissolved, and no
individual unit is greater than 25%
dissolved.
25
Stage Number TestedNumber Tested Acceptance CriteriaAcceptance Criteria
B 1B 1 66 Each unit not less than Q + 5 % .
B 2B 2 66
Average of 12 units (B 1 + B 2 ) is equal
to or greater than Q , and no unit is less
than Q – 15 %
B 3B 3 1212
Average of 24 units (B 1 + B 2 + B 3 )
is equal to or greater than Q , not more
than 2 units are less than Q – 15 %,
and no unit is less than Q – 25 % .
.
26
Stage Number TestedNumber Tested Acceptance CriteriaAcceptance Criteria
L 1L 1 66 No individual value lies out side each of the stated range
and no individual value is less than the final test time
L 2L 2 66
Average of 12 value (L 1 + L 2 ) is lies within each of the
stated range and is not less than the stated amount at the
final test time; none is more than 10% of labeled content
outside each of the stated range;and non is more than
10% of labeled content below the stated amount at the
final test time
L 3L 3 1212
Average of 24 value (L 1 + L 2 +L3 ) is lies within each of
the stated range and is not less than the stated amount at
the final test time; Not more than 2 of 24 unit are more
than 10% of labeled content outside each of the stated
range;Not more than 2 of 24 are more than 10% of
labeled content below the stated amount at the final test
time. Non of the units is more than 20% of labeled
content outside each of the stated range or more than
20% of labeled content below the stated amount at the
finaltest time.
27
 Assuming that the determinative step involves spectrophotometry with
the analysis conducted at a given wavelength, several factors may
produce apparently higher dissolution percentages than what was
found in the Assay. Degradation of the compound under the test
conditions is a possibility as is additive interference due to excipients.
These types of interferences should be identified in method
development and validation . Of course, errors in the preparation of the
standard solution(s) could also play a role . Again, careful attention
to detail , such as the requirement to prepare check standards and
familiarity with the absorptivity of the standard solution, can provide
protection against these types of problems. It is important to consider
the possibility that the higher values found in the dissolution sample
may be true. The assay value is typically the result of the analysis of a
composite of multiple dosage units and, as such, represents an average. If
individual dissolution values that are higher than the assay are observed ,
content uniformity might be to blame. The amount available for
dissolution in the higher-than-assay dosage unit may indeed be higher
than the amount in the assay composite. If consistently higher values are
found in dissolution than in the assay, it may indicate that the validating
information for the dissolution test should be reevaluated.
28
 Physical : This calibration is carried out on monthly basis to check
the critical physical parameters of the instrument.(Frequency as per sop)
 Chemical : This is calibration is carried out during installation of the
instrument and after every six month to check the apparatus suitability
(Frequency as per sop)
29
Sr.n.Sr.n. ParameterParameter Acceptance Criteria ( USP )Acceptance Criteria ( USP )
0101 Head Co-PlanarityHead Co-Planarity Perfectly HorizontalPerfectly Horizontal
0202 Rotational SpeedRotational Speed ±± 2 % of the stated value2 % of the stated value
0303 Temperature checkTemperature check 3737 ± 0.5 ° C± 0.5 ° C
0404 Calibration of timerCalibration of timer ±± 2 % of the stated value2 % of the stated value
0505 Wobble checkWobble check NMT 0.5 mm for paddleNMT 0.5 mm for paddle
NMT 1.0 mm for basketNMT 1.0 mm for basket
0606 Distance from paddle / basketDistance from paddle / basket
bottom to the bottom of the jarbottom to the bottom of the jar
2525 ±± 2 mm2 mm
0707 Integrity check and mesh size ofIntegrity check and mesh size of
basketbasket
The mesh should be intact . The no. ofThe mesh should be intact . The no. of
opening should be 40 per linearopening should be 40 per linear
inchinch
0808 Distance between the shaft axis andDistance between the shaft axis and
the vertical axis of the vesselsthe vertical axis of the vessels
The centering should beThe centering should be
<< 2mm2mm
30
 Use Prednisone 10mg Tablets (Current lot)and follow instruction given in related
certificates for standard and test preparation and calculate % of drug release and perform
PVT test
Calculation of %CV: 
 Run 1 : x1,x2, …….., xnin natural log scale, :Ln x1, Ln x2, …….., Ln xn
 Run 2 : xn+1,xn+2, …….., xnin natural log scale, :Ln xn+1, Ln xn+2, …….., Ln x2n
 1st
stage of two-stage for n=6, 7, 8 and Single-stage for n=12, 14:
 GM1 = exp (average (Ln x1: Ln xn))

 % CV = 100*sqrt(exp (var (Ln x1: Ln xn))-1)
 Single-stage or 2nd
stage of two-stage for n=6, 7, 8:
 GM = exp (average((average (Ln x1: Ln xn)), (average (Ln xn+1: Ln x2n)))) = exp (average (Ln x1:
Ln x2n))
 % CV = 100*sqrt(exp (average((var(Ln x1: Ln xn)), (var(Ln xn+1: Ln x2n))))-1)
 exp: exponential (ex
), var: variance, sqrt: square root, * : multiply, 100: conversion factor
to percentage
31
 Complete Validation Toolkit
 Depth Setting Gauge
 Tachometer ( Optical )
 Thermometer
32
 Universal Instrument Level
 Vessel Centering Gauge
 Vibration Meter
 Wobble meter
33
◦ Keep the surroundings clean and tidy of dissolution apparatus.
◦ Any spillage of liquid is to be immediately mopped.
◦ Finally before leaving the place, ensure that the dissolution vessels are
washed, the heater is turned off and the spindles have been removed &
washed
◦ Do not start the heater if there is no water in the dissolution bath up to
the indicated level.
◦ The Bath should be always filled with distilled water only. In order to
avoid germs propagation the liquid can be sterilized with a suitable
preservative (e.g. 0.1% w/v Benzalkonium chloride).
◦ To clean the jars and heater bath do not use any aggressive material or
strong solvents which can spoil the jars
34
◦ Do not hold the stirrer while in operation.
◦ Do not pull or force the paddle or the basket
◦ Do not over tighten the stirring element
◦ It is not possible to lift the stirrer unit, while paddles are rotating so first
stop the stirring process then lift the stirring assembly
◦ Do not disturb the sensor tube while cleaning the tank.
35
36

More Related Content

What's hot

Physical stability tablets & capsules
Physical stability tablets & capsulesPhysical stability tablets & capsules
Physical stability tablets & capsulesShweta Singh
 
Dissolution apparatus.ppt
Dissolution apparatus.pptDissolution apparatus.ppt
Dissolution apparatus.pptVinayak Wani
 
Invitro : dissolution and drug release testing
Invitro : dissolution and drug release testingInvitro : dissolution and drug release testing
Invitro : dissolution and drug release testingDurgadevi Ganesan
 
Methods of Solubility Enhancement
Methods of Solubility EnhancementMethods of Solubility Enhancement
Methods of Solubility EnhancementVishal Shelke
 
Product Stability Studies & Stability Testing
Product Stability Studies & Stability Testing Product Stability Studies & Stability Testing
Product Stability Studies & Stability Testing Amit Attri
 
Dissolution chapter
Dissolution chapter Dissolution chapter
Dissolution chapter Arshad Khan
 
Ipqc and fpqc test for suppositories
Ipqc and fpqc test for suppositoriesIpqc and fpqc test for suppositories
Ipqc and fpqc test for suppositoriesArpitSuralkar
 
Comparision of dissolution profile
Comparision of dissolution profileComparision of dissolution profile
Comparision of dissolution profileRanjith Karanam
 
Validation of dissolution apparatus
Validation of dissolution apparatusValidation of dissolution apparatus
Validation of dissolution apparatusShraddha Kumbhar
 
Dissolution apparatus
Dissolution apparatusDissolution apparatus
Dissolution apparatusPankaj Verma
 
DISSOLUTION TESTING APPARATUS
DISSOLUTION TESTING APPARATUSDISSOLUTION TESTING APPARATUS
DISSOLUTION TESTING APPARATUSBushra S
 
Ich guideline for stability testing
Ich guideline for stability testingIch guideline for stability testing
Ich guideline for stability testingShubham Gore
 
Dissolution Testing Apparatus
Dissolution Testing ApparatusDissolution Testing Apparatus
Dissolution Testing ApparatusSourav Kar
 
GUIDELINES FOR DISSOLUTION TESTING
GUIDELINES FOR DISSOLUTION TESTINGGUIDELINES FOR DISSOLUTION TESTING
GUIDELINES FOR DISSOLUTION TESTINGSagar Savale
 
Clinical significance of be studies
Clinical significance of be studiesClinical significance of be studies
Clinical significance of be studiesDurgadevi Ganesan
 

What's hot (20)

Physical stability tablets & capsules
Physical stability tablets & capsulesPhysical stability tablets & capsules
Physical stability tablets & capsules
 
Dissolution apparatus.ppt
Dissolution apparatus.pptDissolution apparatus.ppt
Dissolution apparatus.ppt
 
Invitro : dissolution and drug release testing
Invitro : dissolution and drug release testingInvitro : dissolution and drug release testing
Invitro : dissolution and drug release testing
 
Methods of Solubility Enhancement
Methods of Solubility EnhancementMethods of Solubility Enhancement
Methods of Solubility Enhancement
 
Product Stability Studies & Stability Testing
Product Stability Studies & Stability Testing Product Stability Studies & Stability Testing
Product Stability Studies & Stability Testing
 
Dissolution Method Development & Validation
Dissolution Method Development & ValidationDissolution Method Development & Validation
Dissolution Method Development & Validation
 
Dissolution chapter
Dissolution chapter Dissolution chapter
Dissolution chapter
 
Disso validation 1
Disso validation 1Disso validation 1
Disso validation 1
 
Ipqc and fpqc test for suppositories
Ipqc and fpqc test for suppositoriesIpqc and fpqc test for suppositories
Ipqc and fpqc test for suppositories
 
Stability studies
Stability studies Stability studies
Stability studies
 
dissolution
dissolutiondissolution
dissolution
 
Comparision of dissolution profile
Comparision of dissolution profileComparision of dissolution profile
Comparision of dissolution profile
 
Validation of dissolution apparatus
Validation of dissolution apparatusValidation of dissolution apparatus
Validation of dissolution apparatus
 
Dissolution apparatus
Dissolution apparatusDissolution apparatus
Dissolution apparatus
 
DISSOLUTION TESTING APPARATUS
DISSOLUTION TESTING APPARATUSDISSOLUTION TESTING APPARATUS
DISSOLUTION TESTING APPARATUS
 
Ich guideline for stability testing
Ich guideline for stability testingIch guideline for stability testing
Ich guideline for stability testing
 
Dissolution Testing Apparatus
Dissolution Testing ApparatusDissolution Testing Apparatus
Dissolution Testing Apparatus
 
GUIDELINES FOR DISSOLUTION TESTING
GUIDELINES FOR DISSOLUTION TESTINGGUIDELINES FOR DISSOLUTION TESTING
GUIDELINES FOR DISSOLUTION TESTING
 
Clinical significance of be studies
Clinical significance of be studiesClinical significance of be studies
Clinical significance of be studies
 
Biorelevant ppt
Biorelevant pptBiorelevant ppt
Biorelevant ppt
 

Similar to Dissolution

Basic Approach to Dissolution Method Development – Challenges and Regulatory ...
Basic Approach to Dissolution Method Development – Challenges and Regulatory ...Basic Approach to Dissolution Method Development – Challenges and Regulatory ...
Basic Approach to Dissolution Method Development – Challenges and Regulatory ...Dr. Harshal Pawar
 
Industrial Pharmacy, Quality control of tablets.pdf
Industrial Pharmacy, Quality control of tablets.pdfIndustrial Pharmacy, Quality control of tablets.pdf
Industrial Pharmacy, Quality control of tablets.pdfAlishaKhatun4
 
In vitro dissolution testing methods
In vitro dissolution testing methodsIn vitro dissolution testing methods
In vitro dissolution testing methodsPNMallikarjun
 
Development of dissolution method.
Development of dissolution method.Development of dissolution method.
Development of dissolution method.akansha10892
 
An orientation lecture For M.Pharm
An orientation lecture For M.Pharm    An orientation lecture For M.Pharm
An orientation lecture For M.Pharm Mcpl Moshi
 
MEETING DISSOLUTION REQUIREMENTS PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION ...
MEETING DISSOLUTION REQUIREMENTS PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION ...MEETING DISSOLUTION REQUIREMENTS PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION ...
MEETING DISSOLUTION REQUIREMENTS PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION ...MukeshKumarBhagat
 
Seminar (advance biopharmaceutics)
Seminar (advance biopharmaceutics)Seminar (advance biopharmaceutics)
Seminar (advance biopharmaceutics)Drx Shubham Badhe
 
Dissolutionapparatus
DissolutionapparatusDissolutionapparatus
DissolutionapparatusRam Kumar
 
Study of consolidation parameters -dissolution profile and pharmacokinetic p...
Study of consolidation parameters -dissolution profile  and pharmacokinetic p...Study of consolidation parameters -dissolution profile  and pharmacokinetic p...
Study of consolidation parameters -dissolution profile and pharmacokinetic p...Alakesh Bharali
 
Quality control tests of tablet
Quality control tests of tabletQuality control tests of tablet
Quality control tests of tabletSarangDalvi
 
Dissolution chapter and different mechansims
Dissolution chapter  and different mechansimsDissolution chapter  and different mechansims
Dissolution chapter and different mechansimsDrAmitVerma7
 
Dissolution and drug release testing.ppt
Dissolution and drug release testing.pptDissolution and drug release testing.ppt
Dissolution and drug release testing.pptPrakashGoudanavar
 
Prodact performance in vitro.pptx
Prodact performance in vitro.pptxProdact performance in vitro.pptx
Prodact performance in vitro.pptxDnyaneshwar Ningule
 
Dissolution and drug release testing.ppt
Dissolution and drug release testing.pptDissolution and drug release testing.ppt
Dissolution and drug release testing.pptPrakashGoudanavar
 

Similar to Dissolution (20)

Basic Approach to Dissolution Method Development – Challenges and Regulatory ...
Basic Approach to Dissolution Method Development – Challenges and Regulatory ...Basic Approach to Dissolution Method Development – Challenges and Regulatory ...
Basic Approach to Dissolution Method Development – Challenges and Regulatory ...
 
IVIVC.pptx
IVIVC.pptxIVIVC.pptx
IVIVC.pptx
 
Industrial Pharmacy, Quality control of tablets.pdf
Industrial Pharmacy, Quality control of tablets.pdfIndustrial Pharmacy, Quality control of tablets.pdf
Industrial Pharmacy, Quality control of tablets.pdf
 
In vitro dissolution testing methods
In vitro dissolution testing methodsIn vitro dissolution testing methods
In vitro dissolution testing methods
 
Development of dissolution method.
Development of dissolution method.Development of dissolution method.
Development of dissolution method.
 
An orientation lecture For M.Pharm
An orientation lecture For M.Pharm    An orientation lecture For M.Pharm
An orientation lecture For M.Pharm
 
MEETING DISSOLUTION REQUIREMENTS PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION ...
MEETING DISSOLUTION REQUIREMENTS PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION ...MEETING DISSOLUTION REQUIREMENTS PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION ...
MEETING DISSOLUTION REQUIREMENTS PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION ...
 
Seminar (advance biopharmaceutics)
Seminar (advance biopharmaceutics)Seminar (advance biopharmaceutics)
Seminar (advance biopharmaceutics)
 
Invitro dissolution
Invitro dissolutionInvitro dissolution
Invitro dissolution
 
Dissolution
DissolutionDissolution
Dissolution
 
In vitro.pptx
In vitro.pptxIn vitro.pptx
In vitro.pptx
 
Dissolutionapparatus
DissolutionapparatusDissolutionapparatus
Dissolutionapparatus
 
Ipqc tests of various dosage form
Ipqc tests of various dosage formIpqc tests of various dosage form
Ipqc tests of various dosage form
 
Study of consolidation parameters -dissolution profile and pharmacokinetic p...
Study of consolidation parameters -dissolution profile  and pharmacokinetic p...Study of consolidation parameters -dissolution profile  and pharmacokinetic p...
Study of consolidation parameters -dissolution profile and pharmacokinetic p...
 
Quality control tests of tablet
Quality control tests of tabletQuality control tests of tablet
Quality control tests of tablet
 
Dissolution chapter and different mechansims
Dissolution chapter  and different mechansimsDissolution chapter  and different mechansims
Dissolution chapter and different mechansims
 
validation of disso method 2.pdf
validation of disso method  2.pdfvalidation of disso method  2.pdf
validation of disso method 2.pdf
 
Dissolution and drug release testing.ppt
Dissolution and drug release testing.pptDissolution and drug release testing.ppt
Dissolution and drug release testing.ppt
 
Prodact performance in vitro.pptx
Prodact performance in vitro.pptxProdact performance in vitro.pptx
Prodact performance in vitro.pptx
 
Dissolution and drug release testing.ppt
Dissolution and drug release testing.pptDissolution and drug release testing.ppt
Dissolution and drug release testing.ppt
 

Recently uploaded

INTRODUCTION TO THE FORENSIC SCIENCE.ppt
INTRODUCTION TO THE FORENSIC SCIENCE.pptINTRODUCTION TO THE FORENSIC SCIENCE.ppt
INTRODUCTION TO THE FORENSIC SCIENCE.pptKavitha Krishnan
 
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeTracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeQuick MedTalk
 
Ten lessons learnt as anesthetist.pptx
Ten  lessons  learnt as anesthetist.pptxTen  lessons  learnt as anesthetist.pptx
Ten lessons learnt as anesthetist.pptxtusharchokshi1
 
bleeding disorders 1 Dr.Nannika Pradhan
bleeding disorders 1  Dr.Nannika Pradhanbleeding disorders 1  Dr.Nannika Pradhan
bleeding disorders 1 Dr.Nannika Pradhanthesalberry
 
CANCER SeminarCancer Overview Type of Cancer.pptx
CANCER SeminarCancer Overview  Type of Cancer.pptxCANCER SeminarCancer Overview  Type of Cancer.pptx
CANCER SeminarCancer Overview Type of Cancer.pptxMrStavanUdayKadam
 
(IDE)and(IVD),QMS,21 CFR part820 , 801)
(IDE)and(IVD),QMS,21 CFR part820  , 801)(IDE)and(IVD),QMS,21 CFR part820  , 801)
(IDE)and(IVD),QMS,21 CFR part820 , 801)chahattyagi200
 
Neurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomNeurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomSudhir Kumar
 
SGK VIÊM KHỚP DẠNG THẤP YHN .pdf
SGK VIÊM KHỚP DẠNG THẤP YHN              .pdfSGK VIÊM KHỚP DẠNG THẤP YHN              .pdf
SGK VIÊM KHỚP DẠNG THẤP YHN .pdfHongBiThi1
 
TARGET DELINEATION IN RECTUM CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM  CANCER BY DR KANHUTARGET DELINEATION IN RECTUM  CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM CANCER BY DR KANHUKanhu Charan
 
Explaining "pathology" in digital pathology
Explaining "pathology" in digital pathologyExplaining "pathology" in digital pathology
Explaining "pathology" in digital pathologyYves Sucaet
 
airway management recorded for S2.pptx
airway management  recorded  for S2.pptxairway management  recorded  for S2.pptx
airway management recorded for S2.pptxnakera38
 
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdfSGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdfHongBiThi1
 
Brief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptxBrief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptxTina Purnat
 
Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)Ahmad Thanin
 
Derma Pharmaceutical Franchise Company - Solace Biotech Limited
Derma Pharmaceutical Franchise Company - Solace Biotech LimitedDerma Pharmaceutical Franchise Company - Solace Biotech Limited
Derma Pharmaceutical Franchise Company - Solace Biotech LimitedSBL DIGITAL
 
Thyroid hormones- synthesis, secretion, functions and disorders
Thyroid hormones- synthesis, secretion, functions and disordersThyroid hormones- synthesis, secretion, functions and disorders
Thyroid hormones- synthesis, secretion, functions and disordersSai Sailesh Kumar Goothy
 
HERPES SIMPLEX VIRUS 12032019 TUESDAY pptx
HERPES SIMPLEX VIRUS 12032019 TUESDAY  pptxHERPES SIMPLEX VIRUS 12032019 TUESDAY  pptx
HERPES SIMPLEX VIRUS 12032019 TUESDAY pptxPulkitMittal54
 
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptxNECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptxSizan Thapa
 
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALKLaryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALKQuick MedTalk
 

Recently uploaded (20)

Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders ...
Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders ...Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders ...
Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders ...
 
INTRODUCTION TO THE FORENSIC SCIENCE.ppt
INTRODUCTION TO THE FORENSIC SCIENCE.pptINTRODUCTION TO THE FORENSIC SCIENCE.ppt
INTRODUCTION TO THE FORENSIC SCIENCE.ppt
 
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on timeTracheostomy .pdf ENT by QuickMedTALK. getting things done on time
Tracheostomy .pdf ENT by QuickMedTALK. getting things done on time
 
Ten lessons learnt as anesthetist.pptx
Ten  lessons  learnt as anesthetist.pptxTen  lessons  learnt as anesthetist.pptx
Ten lessons learnt as anesthetist.pptx
 
bleeding disorders 1 Dr.Nannika Pradhan
bleeding disorders 1  Dr.Nannika Pradhanbleeding disorders 1  Dr.Nannika Pradhan
bleeding disorders 1 Dr.Nannika Pradhan
 
CANCER SeminarCancer Overview Type of Cancer.pptx
CANCER SeminarCancer Overview  Type of Cancer.pptxCANCER SeminarCancer Overview  Type of Cancer.pptx
CANCER SeminarCancer Overview Type of Cancer.pptx
 
(IDE)and(IVD),QMS,21 CFR part820 , 801)
(IDE)and(IVD),QMS,21 CFR part820  , 801)(IDE)and(IVD),QMS,21 CFR part820  , 801)
(IDE)and(IVD),QMS,21 CFR part820 , 801)
 
Neurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency RoomNeurological Evaluation of Acute Ischemic stroke in Emergency Room
Neurological Evaluation of Acute Ischemic stroke in Emergency Room
 
SGK VIÊM KHỚP DẠNG THẤP YHN .pdf
SGK VIÊM KHỚP DẠNG THẤP YHN              .pdfSGK VIÊM KHỚP DẠNG THẤP YHN              .pdf
SGK VIÊM KHỚP DẠNG THẤP YHN .pdf
 
TARGET DELINEATION IN RECTUM CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM  CANCER BY DR KANHUTARGET DELINEATION IN RECTUM  CANCER BY DR KANHU
TARGET DELINEATION IN RECTUM CANCER BY DR KANHU
 
Explaining "pathology" in digital pathology
Explaining "pathology" in digital pathologyExplaining "pathology" in digital pathology
Explaining "pathology" in digital pathology
 
airway management recorded for S2.pptx
airway management  recorded  for S2.pptxairway management  recorded  for S2.pptx
airway management recorded for S2.pptx
 
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdfSGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
SGK BỆNH LÝ GOUT YHN hay lắm nha aaaa.pdf
 
Brief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptxBrief introduction to information ecosystem x public health.pptx
Brief introduction to information ecosystem x public health.pptx
 
Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)Methicillin-resistant Staphylococcus Aureus (MRSA)
Methicillin-resistant Staphylococcus Aureus (MRSA)
 
Derma Pharmaceutical Franchise Company - Solace Biotech Limited
Derma Pharmaceutical Franchise Company - Solace Biotech LimitedDerma Pharmaceutical Franchise Company - Solace Biotech Limited
Derma Pharmaceutical Franchise Company - Solace Biotech Limited
 
Thyroid hormones- synthesis, secretion, functions and disorders
Thyroid hormones- synthesis, secretion, functions and disordersThyroid hormones- synthesis, secretion, functions and disorders
Thyroid hormones- synthesis, secretion, functions and disorders
 
HERPES SIMPLEX VIRUS 12032019 TUESDAY pptx
HERPES SIMPLEX VIRUS 12032019 TUESDAY  pptxHERPES SIMPLEX VIRUS 12032019 TUESDAY  pptx
HERPES SIMPLEX VIRUS 12032019 TUESDAY pptx
 
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptxNECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
NECROSIS FOR MBBS FIRST YEAR STUDENTS MADE EASY.pptx
 
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALKLaryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
Laryngeal papillomatosis .pdf ENT BY QUICKMEDTALK
 

Dissolution

  • 2.  The dissolution testing serves as an important tool for characterizing the biopharmaceutical quality of a product at different stages in the life cycle . In early drug development , in vitro dissolution properties are supportive for choosing between different alternative formulation candidates for further development and for evaluation of active ingredients / drug substances .  Tablets or capsules taken orally remain one of the most effective means of treatment available. The effectiveness of such dosage forms relies on the drug dissolving in the fluids of the gastrointestinal tract prior to absorption into the systemic circulation.  “Dissolution is a standardized method for measuring the rate of drug release from a dosage form and their solubilization” 2
  • 3.  The principle function of the dissolution test may be summarized as follows: •Optimization of therapeutic effectiveness during product development and stability assessment. •Routine assessment of production quality to ensure uniformity between production lots. •Assessment of ‘bioequivalence’, that is to say,production of the same biological availability from discrete batches of products from one or different manufacturers. ••Provide process control and quality assuranceProvide process control and quality assurance •Prediction of ‘in-vivo’ availability, i.e. bioavailability •To create a dissolution profile •To asses the batch to batch quality •It provide pharmaceutical scientist relationship between an in vitro characteristic of a dosage form, and its in vivo performance. 3
  • 4. •Nature of drug. • pH. • Solubility. • Dissociation constant. • Particle size. • Proper selection of dissolution agent. • Setting of in process parameters. • Hardness. • Thickness. • Physical parameters of tester. • Temperature • Media deaeration • Medium volume etc. 4
  • 5. TESTTEST IPIP BPBP USPUSP TemperatureTemperature 36.5 to 37.536.5 to 37.5 °C°C 36.5 to 37.536.5 to 37.5 °C°C 3737± 0.5 °C± 0.5 °C pH of MediumpH of Medium ± 0.05± 0.05 ± 0.05± 0.05 ± 0.05± 0.05 Time forTime for withdrawalwithdrawal ± 2 %± 2 % -- ± 2 %± 2 % Distance betweenDistance between bottom of paddlebottom of paddle and jarand jar 23 – 27 mm23 – 27 mm 23 – 27 mm23 – 27 mm 2525 ± 2 mm± 2 mm RPMRPM ± 4 %± 4 % ± 4 %± 4 % ± 4 %± 4 % 5
  • 6. Disintegration is defined as that state in which any residue of the unit , except fragments of insoluble coating or capsule shell , remaining on the screen of the test apparatus is a soft mass having no palpably firm core Simply it is break down of dosage in define condition Dissolution Dissolution is a standardized method for measuring the rate of drug release from a dosage form . Dissolution is breakdown as well as release, solubilization of drug Generally performed for API having less solubility. Disintegration 6
  • 7. The impartment apparatus as per USP are:  Type I ( Basket Apparatus ) : The assembly consist of a vessel with a hemispherical bottom, which may be covered , made of glass or other inert , transparent material , a motor , a metallic drive shaft and a cylindrical basket .  Type II ( Paddle Apparatus ) : Use the same assembly from apparatus 1 , expect that a paddle formed from a blade and a shaft is used as the stirring device .  Apparatus 3 ( Reciprocating Cylinder ) : The assembly consist of a set of glass reciprocating cylinders , inert fittings , a screen and a motor and drive assembly to reciprocate cylinders vertically inside the vessels .  Apparatus 4 ( Flow through Cell ) : The assembly consist of a reservoir and a pump for the dissolution medium ; a flow through cell and a water bath 7
  • 8.  Temperature  Shaft RPM  Medium  Bath Level  Vessels  Time 8
  • 9.  Temperature control in tablet dissolution testing is critical as a change in temperature has a linear effect on the dissolution rate. Temperature should be measured with a calibrated thermometer, either analogue or digital, and should normally be 37°C  The specified temperature should be measure in each vessel prior to each run commencing . There is a temptation to only measure temperature in a few of the vessels and assume that they are all the same. This may not necessarily be the case as temperature gradients can occur within a water bath that effect the speed of equilibration of all the vessels.  Most dissolution baths display the temperature of the bath itself but this should not be taken as an indication of the temperature inside the vessel. Typically it is necessary to run the water bath 0.5°C or so above the required temperature to ensure the correct temperature inside the vessel . If plastic vessels are used instead of glass then this may be a greater difference. 9
  • 10.  The USP limit for stirring is ± 4% of the set speed of the test . This level of shaft control was set during the early days of equipment manufacturing where surging motors (this temporarily increased or decreased the speed) were difficult to control . All modern equipment can now control the speed to within ± 0.5 rpm so this problem is rare . However the RPM still needs to be measured periodically with a suitable tachometer.  For Immediate release tablets, baskets at 100 RPM and Paddles at 50 or 75 RPM are commonly used.  The RPM outside 25 and 150 are not appropriate because of inconsistency of hydrodynamics below 25 rpm and turbulence above 150 rpm 10
  • 11.  Selection of dissolution medium is based on the discriminatory capabilities,ruggedness and stability of the analyte in the test medium.  Key factors are solubility of the drug and solution stability.  Properties that can affect the dissolution are release mechanism,disintegration rate presence of solubility enhancers and other excipients.  Another requirement for developing a dissolution procedure is to have sink conditions.  In some cases surfactants are used like SLS or Polysorbate 80. These help to enhance the drug solubility.  Also the medium selection depends upon the location of availability of the drug, for eg  For release in stomach it is water or 0.1n HCl  For release in Intestine it is Buffer pH 6.8  For release in Pancreas it is buffer containing enzymes 11
  • 12.  Media degassing is important as dissolved gases can causes bubbles to form , which may change the result of the test .  High results can occur when the bubbles adhere to the surface of the tablet particles, increase their buoyancy, and raise them to a higher part of the vessel where the media flow is quicker.  Lower results can occur if the bubbles adhere to the surface of the basket or the tablet forming a physical barrier between the tablet and the media. 12
  • 13.  Helium sparging  Heating and filtering  Vacuum degassing Method % Reduction (approximate) USP 84.9 ± 11% Filtering only at room temperature 65 ± 3% Heating to 45°C 10 ± 14% Boiling 49 ± 3% Vacuum degassing 50-90% 13
  • 14.  A releasing medium is the one that promotes solubilization of the drug substance from a pharmaceutical dosage form without further qualification .  A discriminating medium is the one where the more subtle aspects of the pharmaceutical dosage form can be differentiated by observing their individual rates of dissolution . Particle size , crystal form, salt form , presence of water of hydration, differences in the manufacturing processes ,and so forth , may all affect the dissolution performance . The dissolution test should be sensitive to any attribute that may affect the in vivo performance of the product. 14
  • 15.  The level of a dissolution bath is often overlooked. It should not be assumed that the laboratory bench is level . This is one of the parameters that should be checked on installation and some dissolution testers have an in-built level checking device.  Testers which are not level can give erroneous results and the media rotation is not linear within the vessel.  Level should be tested front to back as well as side to side . A calibrated level will provide an accurate measurement of this. If the bath is moved for any reason then this parameter will need to be re-checked. 15
  • 16.  Vessel design is something that is often overlooked by the analyst. The USP allows for a significant variation in the specification of the vessels with a height of 160-170mm and an ID of 98-106mm. This variation means that if vessels are changed in the bath then the paddle height and centering measurements need to be rechecked. If the vessels are serialized then they should be kept in the same position. As well as the physical dimensions the vessels should be smooth and scrupulously clean . Small ridges on the inside of the vessel can greatly increase the dissolution rate whilst scratches and sticky or gummy patches can reduce them. 16
  • 17. 17
  • 18.  Introduction to Sampling : Almost every dissolution test relies on samples being taken to produce a result and anything which affects the accuracy of a sample should therefore be avoided. Sampling errors are very common and are often the cause of erroneous results. The sampling position is critical but so to is the type of sampling probe used.  The sampling position is important particularly for tests with baskets as there is often a concentration profile between the bottom of the vessels and the stirring element . It is less noticeable with paddles as the extra agitation provides for a more uniform flow profile. The USP defines the sampling point as "A zone half way between the top of the media and top of the paddle or basket not less than 1cm from the vessel wall". Therefore the sampling position will be different for 500ml and 900ml tests. This can create problems for equipment that uses ‘through the shaft’ sampling. 18
  • 19.  "A zone half way between the top of the media and top of the paddle or basket not less than 1 cm from the vessel wall". 19
  • 20. 20
  • 21. 21
  • 22.  Where a single time specification is given , the test may be concluded in a shorter period . If two or more times are specified , specimens are to be withdrawn only at the stated times, within a tolerance of ± 2 % .  The duration of test is decided by finding the optimum time required for reaching the peak plasma concentration “ Q “ Value : The quantity , Q , is the amount of dissolved active ingredient specified in the individual monograph , expressed as a percentage of the labeled content 22
  • 23.  After the dissolution is over , combine the equal volumes of filtered solutions of the six or twelve individual specimens withdrawn and use this solution as a pooled solution . StagesStages NumberNumber TestedTested Acceptance CriteriaAcceptance Criteria S 1S 1 66 Average amount dissolved is not lessAverage amount dissolved is not less than Q + 10 % .than Q + 10 % . S 2S 2 66 Average amount dissolved ( S 1 + S 2 ) isAverage amount dissolved ( S 1 + S 2 ) is equal to or greater than Q + 5 % .equal to or greater than Q + 5 % . S 3S 3 1212 Average amount dissolved ( S 1 + S 2 + S 3)Average amount dissolved ( S 1 + S 2 + S 3) is equal to or greater than Q .is equal to or greater than Q . 23
  • 24. Stage Number TestedNumber Tested Acceptance CriteriaAcceptance Criteria S 1S 1 66 Each unit not less than Q + 5 % . S 2S 2 66 Average of 12 units (S 1 + S 2 ) is equal to or greater than Q , and no unit is less than Q – 15 % . S 3S 3 1212 Average of 24 units (S 1 + S 2 + S 3 ) is equal to or greater than Q , not more than 2 units are less than Q – 15 %, and no unit is less than Q – 25 % . 24
  • 25. Stage Number TestedNumber Tested Acceptance CriteriaAcceptance Criteria A 1A 1 66 No individual value exceed 10% dissolved. A 2A 2 66 Average of 12 units (A 1 + A 2 ) is Not more than 10% dissolved,and no individual unit is greater than 25% dissolved. A 3A 3 1212 Average of 24 units (A 1 + A 2 +A3 ) is Not more than 10% dissolved, and no individual unit is greater than 25% dissolved. 25
  • 26. Stage Number TestedNumber Tested Acceptance CriteriaAcceptance Criteria B 1B 1 66 Each unit not less than Q + 5 % . B 2B 2 66 Average of 12 units (B 1 + B 2 ) is equal to or greater than Q , and no unit is less than Q – 15 % B 3B 3 1212 Average of 24 units (B 1 + B 2 + B 3 ) is equal to or greater than Q , not more than 2 units are less than Q – 15 %, and no unit is less than Q – 25 % . . 26
  • 27. Stage Number TestedNumber Tested Acceptance CriteriaAcceptance Criteria L 1L 1 66 No individual value lies out side each of the stated range and no individual value is less than the final test time L 2L 2 66 Average of 12 value (L 1 + L 2 ) is lies within each of the stated range and is not less than the stated amount at the final test time; none is more than 10% of labeled content outside each of the stated range;and non is more than 10% of labeled content below the stated amount at the final test time L 3L 3 1212 Average of 24 value (L 1 + L 2 +L3 ) is lies within each of the stated range and is not less than the stated amount at the final test time; Not more than 2 of 24 unit are more than 10% of labeled content outside each of the stated range;Not more than 2 of 24 are more than 10% of labeled content below the stated amount at the final test time. Non of the units is more than 20% of labeled content outside each of the stated range or more than 20% of labeled content below the stated amount at the finaltest time. 27
  • 28.  Assuming that the determinative step involves spectrophotometry with the analysis conducted at a given wavelength, several factors may produce apparently higher dissolution percentages than what was found in the Assay. Degradation of the compound under the test conditions is a possibility as is additive interference due to excipients. These types of interferences should be identified in method development and validation . Of course, errors in the preparation of the standard solution(s) could also play a role . Again, careful attention to detail , such as the requirement to prepare check standards and familiarity with the absorptivity of the standard solution, can provide protection against these types of problems. It is important to consider the possibility that the higher values found in the dissolution sample may be true. The assay value is typically the result of the analysis of a composite of multiple dosage units and, as such, represents an average. If individual dissolution values that are higher than the assay are observed , content uniformity might be to blame. The amount available for dissolution in the higher-than-assay dosage unit may indeed be higher than the amount in the assay composite. If consistently higher values are found in dissolution than in the assay, it may indicate that the validating information for the dissolution test should be reevaluated. 28
  • 29.  Physical : This calibration is carried out on monthly basis to check the critical physical parameters of the instrument.(Frequency as per sop)  Chemical : This is calibration is carried out during installation of the instrument and after every six month to check the apparatus suitability (Frequency as per sop) 29
  • 30. Sr.n.Sr.n. ParameterParameter Acceptance Criteria ( USP )Acceptance Criteria ( USP ) 0101 Head Co-PlanarityHead Co-Planarity Perfectly HorizontalPerfectly Horizontal 0202 Rotational SpeedRotational Speed ±± 2 % of the stated value2 % of the stated value 0303 Temperature checkTemperature check 3737 ± 0.5 ° C± 0.5 ° C 0404 Calibration of timerCalibration of timer ±± 2 % of the stated value2 % of the stated value 0505 Wobble checkWobble check NMT 0.5 mm for paddleNMT 0.5 mm for paddle NMT 1.0 mm for basketNMT 1.0 mm for basket 0606 Distance from paddle / basketDistance from paddle / basket bottom to the bottom of the jarbottom to the bottom of the jar 2525 ±± 2 mm2 mm 0707 Integrity check and mesh size ofIntegrity check and mesh size of basketbasket The mesh should be intact . The no. ofThe mesh should be intact . The no. of opening should be 40 per linearopening should be 40 per linear inchinch 0808 Distance between the shaft axis andDistance between the shaft axis and the vertical axis of the vesselsthe vertical axis of the vessels The centering should beThe centering should be << 2mm2mm 30
  • 31.  Use Prednisone 10mg Tablets (Current lot)and follow instruction given in related certificates for standard and test preparation and calculate % of drug release and perform PVT test Calculation of %CV:   Run 1 : x1,x2, …….., xnin natural log scale, :Ln x1, Ln x2, …….., Ln xn  Run 2 : xn+1,xn+2, …….., xnin natural log scale, :Ln xn+1, Ln xn+2, …….., Ln x2n  1st stage of two-stage for n=6, 7, 8 and Single-stage for n=12, 14:  GM1 = exp (average (Ln x1: Ln xn))   % CV = 100*sqrt(exp (var (Ln x1: Ln xn))-1)  Single-stage or 2nd stage of two-stage for n=6, 7, 8:  GM = exp (average((average (Ln x1: Ln xn)), (average (Ln xn+1: Ln x2n)))) = exp (average (Ln x1: Ln x2n))  % CV = 100*sqrt(exp (average((var(Ln x1: Ln xn)), (var(Ln xn+1: Ln x2n))))-1)  exp: exponential (ex ), var: variance, sqrt: square root, * : multiply, 100: conversion factor to percentage 31
  • 32.  Complete Validation Toolkit  Depth Setting Gauge  Tachometer ( Optical )  Thermometer 32
  • 33.  Universal Instrument Level  Vessel Centering Gauge  Vibration Meter  Wobble meter 33
  • 34. ◦ Keep the surroundings clean and tidy of dissolution apparatus. ◦ Any spillage of liquid is to be immediately mopped. ◦ Finally before leaving the place, ensure that the dissolution vessels are washed, the heater is turned off and the spindles have been removed & washed ◦ Do not start the heater if there is no water in the dissolution bath up to the indicated level. ◦ The Bath should be always filled with distilled water only. In order to avoid germs propagation the liquid can be sterilized with a suitable preservative (e.g. 0.1% w/v Benzalkonium chloride). ◦ To clean the jars and heater bath do not use any aggressive material or strong solvents which can spoil the jars 34
  • 35. ◦ Do not hold the stirrer while in operation. ◦ Do not pull or force the paddle or the basket ◦ Do not over tighten the stirring element ◦ It is not possible to lift the stirrer unit, while paddles are rotating so first stop the stirring process then lift the stirring assembly ◦ Do not disturb the sensor tube while cleaning the tank. 35
  • 36. 36