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QUALITY CONTROL OF
SOLID DOSAGE FORMS

TABLETS
 Tablets are solid dosage forms containing one or
more active ingredients.
 Unit-dose dosage forms.
 Obtained by single or multiple compression.
 May be uncoated or coated.
 They are usually intended for oral administration.

QC TESTS OF TABLETS
 Classified into 2 groups:
Physical tests Chemical tests
 Weight variation
 Hardness
 Thickness & diameter
 Friability
 Disintegration time
 Assay
 Content uniformity
 Dissolution

Weight variation
 Actual weight of tablet;
 determined by diameter of die &
 weight adjustment knob on machine.
 Known as – compression weight.
 Weight control – routinely adjusted to ensure that
specified wt; is reproduced.

Cont...
 Limits for uncoated tablets (USP):
 For 20 tablets
Average tablet weight Percentage deviation allowed
18 tablets 2 tablets
130 mg or less ±10% ±20%
130 to 324 mg ± 7.5% ±15%
More than 324 ± 5% ±10%

Procedure
 Weigh 20 tablets as a whole.
 Divide total weight by 20 – average wt.
 Weigh 20 tabs – individually.
 Calculate the result.

Hardness
 Important test – related to solubility.
 Mechanical hardness testers used commonly are:
 Strong-Cobb
 Stokes monsanto
 Eureka
 Pfizer
 Measures resistance to crushing of tablet.
 Average hardness limit = 5-10 kg/cm2
 German made instruments – scale in Newton (1N=9.8kg)

Manual
Strong-Cobb type
Stokes monsanto type
Pfizer type
DIFFERENT HARDNESS TESTERS

Procedure
 Eureka instrument – breaking force applied by a
beam fastened to one end to a pivot.
 Motor moves beam at constant speed.
 Increases force against tablet, on which other end of
beam rests.
 When tablet breaks – a micro-switch is activated,
that stops motor.
 Indicator shows the breaking strength on scale in kgs.

Cont...
 Proper hardness for tablets ensures that the tablet
withstand the shock of:
 handling,
 packing &
 shipping.

Thickness & Diameter
 Measured by vernier callipers.
 Initially an in-process control during
production.
 Thickness – directly related to
hardness.
 Limits for tablet thickness – depends on
tablet weight.
 Purpose – trouble free packing.

Cont...
 Thickness range = 2-4 mm (depending on diameter
of tablet).
 Diameter range = 4-13 mm.
 Apply on tablets which are not sugar coated,
enteric or film coated.
 Deviation allowed = ±5% of stated diameter.
 For diameter exceeding 12.5 mm = ±3% deviation.

Friability
 Due to friction & shock – tablets chip, cap or break.
 So equipment Roche friabilator developed.
 Cause self abrasion of tablets;
 as cylinder section rotates.
 Tablets undergo shock – as they fall 6 inches on
each turn.
 Operation time = 4 minute or 100 revolutions.
 i.e., 25 rev/min.

Cont...
 Tablets weighed & compared to their original
weight.
 Loss due to friction or abrasion – measure of
friability.
 Value – expressed in % w/w.
 Limits of wt; loss < 0.8 %.
 If capping or breaking – friability values not
calculated.
 Tablet more friable – when lose moisture.

Disintegration
 Limits of DT = 5-30 min in different
pharmacopoeias.
 Attempts to simulate in-vivo conditions.
 Test – doesn’t correlate with physiological
conditions.
 Test – cause breakdown/disintegration of tablet.
 Test doesn’t cause complete solution of tablet.

Cont...
 Complete disintegration – a state in which any
residue of tablet remaining on screen of apparatus
is a soft mass having no firm core.
 Except fragments of insoluble coating.
 USP disintegration test – specific apparatus &
method.
 describes test procedure for each type of tablet.

Cont...
 Disintegration time – given in individual
monographs & tested for compliance.
 Except for tablets – troches, chewable, sustained
release.
 So according to type of tablet – procedure is
applied on 6 or more tablets.

Apparatus
Consists of:
 Basket-rack assembly – holds the tablets.
 Suitable vessel – for immersion fluid (1L beaker)
 Thermostatic arrangement – heating fluid between
35 & 39 °C.
 Device – for raising and lowering basket in
immersion fluid.
 frequency 28 to 32 cycles/min.
 through a distance = 5-6 cm.

Cont...
 Volume of fluid in vessel at;
 Upward stroke – wire mesh 2.5 cm below surface of fluid.
 Downward stroke – wire mesh 2.5 cm above bottom of
vessel.
 Time for;
 upward stroke = downward stroke
 Change in stroke direction – smooth transition.

Cont...
 Basket-rack assembly – consists of 6 open-ended
glass tubes.
 Each glass tube;
 Length = 7.75 ± 0.25 cm
 Internal diameter = 21.5 mm
 Wall thickness = 2 mm
 Tubes held in vertical position – by 2 plastic plates.
 Diameter = 9 cm
 Thickness = 6 mm

Cont...
 6 holes in each plate – 24 mm dia.
 Holes – equidistant from centre of plate & equally
spaced.
 To under surface of lower plate – attached a
10-mesh stainless steel gauge.
 Plastic plates supported by stainless steel plates.
 Diameter = 9 cm
 Thickness = 1 mm
 6 holes – 20 mm dia.

Cont...
 Central shaft – attached to stainless steel plate.
 Length = 8 cm
 Parts of apparatus – assembled & held rigidly by 3
blots.
 Design of apparatus – may be changed.
 But specs for glass tubes & mesh sizes – maintained.

Cont...
 Disks – each tube provided with perforated
cylindrical disk.
 Purpose;
 to obtain solid to solid contact as in stomach.
 to prevent floating tablets from coming out of tubes.
 due to low specific gravity or
 air imprisonment

Cont...
 Disk specifications:
 Thickness = 9.5 ± 0.15 mm
 Diameter = 20.7 ± 0.15 mm
 Made up of transparent plastic material.
 Sp; gravity – 1.18 to 1.120
 Five 2mm holes in disks.
 One hole in middle.
 4 parallel with it equally spaced (at 6mm radius).

Cont...
 On sides of cylindrical disks – 4 notches equally
spaced.
 Notches – form V-shaped planes; perpendicular to
ends of disk.
 Notch opening on bottom of cylinder = 1.60 mm
 Notch openings on top = 9.5 mm
 All surfaces of disk – smooth.

Procedure
Uncoated tablets:
 Place 1 tablet in each of six tubes.
 A disk to each tube is added.
 Operate apparatus.
 Water as immersion fluid – unless another specified
in individual monograph.
 Fluid temp = 37 ± 2 °C.
 Time limit for operation – specified in monograph.

 At end of time limit – lift basket from fluid.
 Observe tablets.
 All tablets – should be disintegrated completely.
 If 1 or 2 tablets fail to disintegrate ;
 repeat test on 12 additional tablets.
 16 out of 18 tabs – must disintegrate completely.

Cont...
Plain coated tablets:
 Place 1 tablet in each of six tubes of basket.
 If tablet has external soluble coating – immerse basket
in water at room temp; for 5 minutes.
 A disk to each tube is added.
 Operate apparatus.
 Simulated gastric fluid – as immersion fluid.
 Fluid temp; = 37 ± 2 °C.
 Time limit for operation – 30 min.

Cont...
Enteric-coated tablets:
 Place 1 tablet in each of six tubes of basket.
 If tablet has external soluble coating – immerse basket
in water at room temp; for 5 minutes.
 Operate apparatus without disks.
 Simulated gastric fluid – as immersion fluid.
 Fluid temp; = 37 ± 2 °C.

 After 1 hr – lift basket & observe tabs.
 No disintegration, cracking or softening of tablets.
 Then add disk to each tube.
 Use simulated intestinal fluid – as immersion fluid.
 Operate – for 2 hrs + time limit specified in
individual monograph.
 At end of time limit – lift basket & observe tablets.
 Limits – same as for uncoated tablets.

Cont...
Buccal tablets:
 Apply test as for uncoated tabs –but don’t use
disks.
 Time limit for operation – 4 hrs.
 Limits – same as for uncoated tabs.
Sublingual tablets:
 Apply test as for uncoated tabs –but don’t use
disks.
 Time limit for operation – 2 min.
 Limits – same as for uncoated tabs.

Assay
 1st
step in assay – grinding of 20 tabs.
 Analysis of an aliquot – representing a certain
amount of drug, normally in single unit.
 Method of analysis – prescribed in monograph.
 Results – as percentage of active drug in tablet.
 Compared with limits in monograph.

Content uniformity
 When ingredients of tablet granulation are
homogenous – tablet weigh test can be considered
as measure of drug content.
 Content uniformity test performed – when individual
monograph requires.
 30 tabs selected.
 Out of which – 10 tabs assayed individually.

Cont...
 For 10 individual tabs:
 All tabs = 85 to 115% of average limit in monograph.
 If;
 9 tabs = 85 to 115% of average limit in monograph.
 1 tab = 75 to 125%
 Then; assay remaining 20 tabs.
 So for total 30 tabs:
 29 tabs = 85 to 115% of average limit in monograph.
 1 tab = 75 to 125%

Dissolution
 Drugs having solubility – greater than 1% w/v, have
no problem.
 But drugs having lower solubility – dissolution systems
are designed.
 So test not used for all drugs.
 USP 19 – recommends dissolution for 15 dosage
forms of different drugs.
 USP 20 – 60 drugs
 USP 21 (1985) – 400 drugs

Cont...
 Used to determine dissolution characteristics of solid
dosage forms.
 Suitable dissolution characteristics – important
property of drug product.
 Because drug absorption depends upon drug in
dissolved state.
 Two methods used for dissolution.
 Method I & method II
 Use method – prescribed in individual monograph.

Method I (apparatus 1)
Rotatory basket method
 Apparatus – consists of following:
 covered vessel – made of plastic or other transparent
material.
 motor
 metallic drive shaft
 cylindrical basket
 constant temp. bath

Cont...
 Vessel – immersed in suitable water bath.
 Water bath – maintain temperature at 37 ± 0.5°C.
 The vessel – cylindrical with slightly concave bottom.
 Height = 16 cm
 Internal diameter = 10 cm
 Capacity = 1000 ml
 Sides are flanged near top – to accept a fitted cover.

Cont...
 Cover has 4 ports – one of which is centred.
 Shaft of motor placed in centre port.
 One port for insertion of thermometer.
 1 port – for sample removal &
 1 port – for dissolution medium replacement.

Cont...
 Motor – fitted with speed regulating device.
 Speed limit of motor = 25 to 200 rpm
 Maintained – as mentioned in monograph, within ±5%.
 Shaft
 Length = 30 cm
 Diameter = 6mm
 Can be raised or lowered to position the basket.
 Shaft is centred – so basket rotates smoothly.

Cont...
 Basket – 2 parts.
 Top – attached to shaft (solid metal having 2 mm vent).
 Fitted to lower part by 3 clips – that allow removal of lower
part.
 Detachable part (lower part) – made of 40 mesh
stainless steel cloth (sieve opening = 420µm).
 Mesh is in the form of cylinder.
 Height = 3.66 cm
 Diameter= 2.5cm

Cont...
 Gold plated basket – recommended for dilute acid
media.
 Dissolution medium – as specified in individual
monograph.

Procedure
 Take 900ml dissolution medium in vessel.
 Vessel – already immersed in constant temp. Bath.
 Allow dissolution medium to – temp. 37 ± 0.5 °C.
 Place 1 tablet in the basket.
 Assemble apparatus & immerse basket in vessel.
 distance b/w basket & bottom of vessel = 2 ± 0.2cm.
 Rotate basket at rate – specified in individual
monograph.

Cont...
 After time specified – withdraw samples for
analysis.
 Analysis method – specified in individual monograph.
 Repeat test on 5 additional tablets.
 Limits
 If 1 or 2 tablets fail – repeat test on 6 additional
tablets.
 10 out of 12 tabs – must meet the requirements.

Method I (apparatus 2)
Paddle method
 Apparatus – same as apparatus 1.
 Except:
 Paddle (formed from blade) – replaced with basket.
 Distance b/w paddle & bottom of vessel = 2.5 ± 0.2cm.
 Dosage unit is allowed to sink to the bottom of the vessel
– before rotation of paddle.
 Small wire helix may be attached or placed over
dosage units.
in order to prevent floating.

Method II
Distegration appartus for dissolution
 Apparatus – same apparatus & basket rack
assembly as described under tablet disintegration
test.
 Except:
 Replace 10 mesh stainless steel cloth in basket rack
assembly – with 40 mesh.
 Also cover top of assembly with 40 mesh.

Cont...
 Adjust vessel in such a way so on downward stroke:
 Distance between assembly & bottom of vessel = 1± 0.1cm.
 Dissolution medium & procedure :
 as specified in monograph.

CAPSULES
 Capsules are solid dosage forms in which the
medication contained within gelatine shells.
 Medication may be – a powder, a liquid or a
semisolid mass.
 Usually intended to be administered orally.
 Two types – soft gelatine & hard gelatine capsules.

QC TESTS FOR CAPSULES
 Tests for capsules:
 Uniformity of weight
 Disintegration test
 Assay of active ingredients
 Content uniformity test (same as for tablets)
 Dissolution test (same as for tablets)

Uniformity of weight
 Two methods used:
 Method A
 for capsules with dry content.
 Method B
 for capsules with liquid or paste.

Method A
 Weigh a capsule.
 Open it – without loss of shell material.
 Remove contents & weigh all parts of shell.
 Difference between weight represent – weight of
contents.

Cont...
 Perform test for total of 20 caps.
 Calculate the average weight.
 Limits for weight variation:
Average capsule weight Percentage deviation allowed
18 capsules 2 capsules
120 mg or less ±10% ±20%
More than 120 mg ± 7.5% ±15%

Method B
 Weigh a capsule.
 Open it without loss of material.
 Express as much contents as possible.
 Wash shell with ether & discard washings.
 Allow shell to stand – until odour of ether is no longer
noticeable.
 Then weigh the shell.

Cont...
 Difference between weight represent – weight of
contents.
 Perform test for total of 10 caps.
 Calculate the average weight.
 Limits for weight variation:
Average capsule weight Percentage deviation allowed
9 capsules 1 capsule
All weights ±7.5% ±15%

Assay of active ingredients
 1st
step in assay – take contents of 20 capsules.
 Analysis of an aliquot – representing a certain
amount of drug, normally in single unit.
 Method of analysis – prescribed in monograph.
 Results – as percentage of active drug in tablet.
 Compared with limits in monograph.

Disintegration test
Apparatus (B.P) – consists of:
 Glass tube
 Length = 80-100 mm
 Internal diameter = 28 mm
 External diameter = 30-31mm
 Wire gauze (mesh 10) – fitted to lower end of
tube.
 To form a basket.
 Mesh 10 = 1.70mm (pore size)

Cont...
 Glass cylinder – with flat base.
 Internal diameter = 45 mm
 Contain water – not less than 15cm deep.
 Water temp. = 36-38 C
 Basket suspended centrally in cylinder.
 So that can be raised & lowered repeatedly.

Method
 Place 5 capsules in basket.
 Basket raised & lowered at 30 times/min.
 Capsules disintegrated – if no particle of solid material
present.
 Time for 5 capsules = 15 min
 Unless stated in individual monograph.
 If test fails – because of capsules aggregation
 Repeat on 5 caps – but individually.
 Longest time taken by any one capsule – disintegration
time.

Cont...
 BP used above mentioned apparatus – before
1980.
 In 1980 – BP adopted USP disintegration
apparatus.
USP method:
 Same as for uncoated tablets.
 Except – upper plate of basket rack assembly,
covered with removable wire cloth of mesh 10.

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