2.1 Define tablets. Classify different type of tablets with examples.

Tablets are solid dosage forms containing medicinal substances with or without suitable
diluents, prepared by compression or molding methods. They remain the most widely
used dosage form due to their convenience, accuracy, stability, and manufacturing
efficiency.
Tablets can be classified based on route of administration:
1. Oral tablets:
o Conventional immediate-release tablets (e.g., paracetamol tablets)
o Modified-release tablets:
▪ Sustained-release (e.g., Glucophage XR)
▪ Delayed-release (e.g., enteric-coated aspirin)
o Chewable tablets (e.g., antacid tablets, children's vitamins)
o Dispersible tablets (e.g., dispersible aspirin)
o Sublingual/buccal tablets (e.g., nitroglycerin sublingual)
o Effervescent tablets (e.g., vitamin C effervescent)
o Orally disintegrating tablets (e.g., Zofran ODT)
2. Non-oral tablets:
o Vaginal tablets (e.g., clotrimazole vaginal tablets)
o Rectal tablets (e.g., bisacodyl suppositories)
o Implantable tablets (e.g., hormonal implants)
Based on manufacturing method:
• Compressed tablets (most common)
• Molded tablets (lower compression force)
• Layered tablets (e.g., Adderall XR with immediate and extended release)
This diversity allows for optimal drug delivery for various therapeutic needs and patient
populations.
2.2 What is Tablet? Classify it and explain wet granulation method.
A tablet is a solid dosage form containing medicinal substances with suitable excipients,
manufactured by compression of uniform volumes of powder/granules. Tablets are
characterized by unit dosing, convenience, stability, and cost-effectiveness.
Classification:
1. By administration route: Oral (conventional, sublingual, buccal, ODT), non-oral
(vaginal, rectal)
2. By release pattern: Immediate-release, modified-release (sustained, delayed)
3. By manufacturing method: Direct compression, wet granulation, dry granulation
4. By functionality: Effervescent, chewable, dispersible, multilayered
Wet granulation method involves:
1. Weighing and blending: Active ingredient and excipients (except lubricants) are
mixed.
2. Binder solution preparation: Binders like PVP or HPMC are dissolved in suitable
solvent (water/alcohol).
3. Wet massing: Binder solution is added gradually to powder blend while mixing
until a cohesive mass forms with proper consistency.
4. Granulation: Wet mass is forced through screens/sieves to form granules.
Methods include traditional forced sieving, high-shear, or fluid-bed granulation.
5. Drying: Granules are dried (tray dryer, fluid bed dryer) to optimal moisture content
(typically 1-3%).
6. Sizing: Dried granules are passed through screens to achieve uniform size
distribution.
7. Lubrication: External phase (lubricants, glidants, disintegrants) is blended with
sized granules.
8. Compression: Final blend is compressed into tablets.
2.3 Describe excipients of tablets with give at least two brand name of each.
Tablet excipients are non-medicinal ingredients essential for manufacturing and
functionality:
1. Diluents/Fillers: Provide bulk and improve powder properties • Microcrystalline
cellulose (Avicel PH101, Emcocel) • Lactose (Tablettose, Pharmatose)
2. Binders: Provide cohesiveness to powder mixture • Povidone/PVP (Kollidon,
Plasdone) • HPMC (Methocel, Pharmacoat)
3. Disintegrants: Facilitate tablet break-up after administration • Croscarmellose
sodium (Ac-Di-Sol, Vivasol) • Sodium starch glycolate (Primojel, Explotab)
4. Lubricants: Reduce friction during ejection, prevent sticking • Magnesium
stearate (Hyqual, Sturcal) • Stearic acid (Hystrene, Pristerene)
5. Glidants: Improve powder flow • Colloidal silicon dioxide (Aerosil, Cab-O-Sil) •
Talc (Luzenac, Talcum)
6. Antiadherents: Prevent sticking to punch faces and die walls • Talc (Luzenac,
Magsil) • Magnesium stearate (Hyqual, Sturcal)
7. Sweeteners/Flavors: Improve taste • Saccharin sodium (Necta Sweet, Sweet'N
Low) • Aspartame (Nutrasweet, Equal)
8. Colorants: Identification, aesthetics • FD&C Blue #1 (Brilliant Blue FCF,
Erioglaucine) • Iron oxide pigments (Sicovit, Ferroxide)
Proper selection of these excipients ensures tablet quality, stability, and therapeutic
effectiveness.
2.4 Write on any two: 1) Diluents 2) Disintegrant 3) Binders.
Diluents: Diluents (fillers) provide necessary bulk to formulations when the active
ingredient is potent and present in small amounts. They ensure practical tablet size and
improve powder properties for processing. Selection criteria include solubility,
hygroscopicity, compressibility, flow properties, and compatibility. Commonly used
diluents include lactose (good compressibility, water-soluble but may cause problems
for lactose-intolerant patients), microcrystalline cellulose (excellent compressibility,
disintegrant properties), dicalcium phosphate (insoluble, good flow, suitable for
moisture-sensitive drugs), and mannitol (non-hygroscopic, pleasant taste, suitable for
chewable tablets). Diluents typically constitute 5-80% of tablet formulations, depending
on drug dose and desired tablet size. Direct compression grades with superior flow and
compaction properties are available for many diluents.
Disintegrants: Disintegrants facilitate tablet break-up into smaller fragments upon
contact with aqueous fluids, increasing surface area for drug dissolution. They function
through various mechanisms: swelling (water absorption causing particles to expand),
wicking (capillary action drawing water into tablet pores), deformation recovery (particles
swell to pre-compression size), and repulsion (electric repulsive forces between
particles). Super-disintegrants like croscarmellose sodium, sodium starch glycolate, and
crospovidone are effective at low concentrations (2-5%) compared to traditional
disintegrants like starch (5-15%). Disintegrants can be incorporated intragranularly
(within granules), extragranularly (after granulation), or both for optimal effect. The
choice and concentration depend on formulation characteristics, manufacturing
method, and desired disintegration time, directly influencing dissolution rate and
bioavailability.
2.5 Give four examples of disintegrating agent.
Four examples of disintegrating agents used in tablet formulations:
1. Croscarmellose sodium (Ac-Di-Sol, Vivasol): A cross-linked form of
carboxymethylcellulose sodium that works through rapid swelling and wicking
mechanisms. Effective at 2-5% concentration, it provides rapid disintegration
without excessive gel formation. It can be used both intragranularly and
extragranularly for optimal effect.
2. Sodium starch glycolate (Primojel, Explotab): A cross-linked derivative of potato
starch that exhibits rapid and extensive swelling with minimal gelling. Used at 2-
8% concentration, it swells up to 300% in volume upon contact with water. Most
effective when used extragranularly due to its tendency to lose some
disintegration capacity during wet granulation.
3. Crospovidone (Polyplasdone, Kollidon CL): A cross-linked polyvinylpyrrolidone
that works primarily through capillary action and high recovery after deformation.
Used at 2-5% concentration, it provides rapid disintegration without gel formation
and works effectively at both low and high tablet compression forces.
4. Low-substituted hydroxypropyl cellulose (L-HPC): A partially substituted
hydroxypropyl ether of cellulose that combines both swelling and wicking
mechanisms. Used at 2-10% concentration, it provides good disintegration while
also functioning as a binder in wet granulation, making it multifunctional.
2.6 Describe the granulation methods for preparation of tablets.
Granulation methods convert fine powder particles into larger agglomerates to improve
flow, prevent segregation, and enhance compressibility for tablet manufacturing:
1. Wet Granulation:
o Powder blending of API and excipients
o Addition of binder solution (aqueous/non-aqueous)
o Wet massing to cohesive consistency
o Wet screening to form granules
o Drying to optimal moisture content
o Dry screening for size uniformity
o Blending with external phase (lubricants, disintegrants)
o Advantages: Improves flow, prevents segregation, handles high drug loads
o Disadvantages: Multiple steps, moisture/heat exposure, time-consuming
2. Dry Granulation:
o Slugging: Compaction of powder into large tablets (slugs)
o Roller Compaction: Compression between rollers to form ribbons
o Milling of compacted material into granules
o Screening to desired particle size
o Lubrication and final blending
o Advantages: Suitable for moisture/heat-sensitive drugs, fewer steps
o Disadvantages: Produces more fines, lower density granules
3. Direct Compression:
o Simple blending of API with directly compressible excipients
o Addition of lubricants/glidants
o Direct compression into tablets
o Advantages: Fewest steps, cost-effective, no moisture/heat exposure
o Disadvantages: Limited to drugs with good inherent compressibility,
sensitive to excipient properties, typically limited to lower drug loads
4. Specialized Granulation Techniques:
o Fluid bed granulation: One-step process combining mixing, granulation,
and drying
o High-shear granulation: Rapid processing with mechanical agitation
o Spray drying: Atomization of drug-excipient solution/suspension
o Hot-melt granulation: Uses meltable binders instead of liquid solvents
Selection depends on drug properties, dose, stability considerations, and equipment
availability.
2.7 Give the examples of binders used for tablet formation. Explain various stages of
granulation process.
Examples of binders used in tablet formulation: • Polyvinylpyrrolidone (PVP/Povidone): 2-
10% • Hydroxypropyl methylcellulose (HPMC): 2-5% • Hydroxypropyl cellulose (HPC): 2-
6% • Methylcellulose: 1-5% • Starch paste: 5-10% • Gelatin: 1-5% • Sodium alginate: 1-
3% • Acacia: 1-5% • Polyethylene glycol: 2-10% • Pregelatinized starch: 5-10%
Stages of granulation process:
1. Material preparation: Active pharmaceutical ingredient and excipients are
weighed, screened to break lumps, and sometimes pretreated (e.g., dried to
reduce moisture content).
2. Dry mixing: Initial blending of API with diluents and other excipients (except
lubricants) to achieve homogeneous distribution using suitable blenders (V-
blender, bin blender, planetary mixer).
3. Wet massing: Addition of binder solution to powder mix while maintaining
continuous agitation until proper cohesive mass forms. Endpoint determination
is critical (power consumption, visual/tactile assessment).
4. Wet screening: Passing wet mass through appropriate size screen to form
granules of desired size and shape.
5. Drying: Removal of granulating solvent to achieve optimal moisture content
(typically 1-3%) using tray dryers, fluid bed dryers, or microwave dryers.
6. Dry screening: Sizing of dried granules to achieve uniform particle size distribution
and break agglomerates.
7. External phase addition: Blending of sized granules with lubricants, glidants, and
sometimes disintegrants.
8. Final blending: Ensuring homogeneous distribution of all components before
compression.
2.8 Differentiate: Dry granulation and direct compression.
Dry Granulation vs. Direct Compression
Process Steps: • Dry granulation: Involves compaction (via slugging or roller
compaction), milling, screening, and lubrication before compression • Direct
compression: Simply requires blending of all ingredients followed by compression
Applicability: • Dry granulation: Suitable for drugs with poor flow but adequate
compressibility, moisture/heat-sensitive materials, and medium-high dose drugs •
Direct compression: Limited to drugs with good inherent compressibility and typically
lower doses (<30%)
Equipment Requirements: • Dry granulation: Requires roller compactor/slug press and
milling equipment • Direct compression: Needs only blending equipment and tablet
press
Excipient Selection: • Dry granulation: More flexible in excipient selection • Direct
compression: Requires specialized directly compressible grades of excipients with
superior flow and compaction properties
Processing Time/Efficiency: • Dry granulation: Intermediate process time, higher energy
consumption • Direct compression: Shortest process time, most economical, lowest
energy consumption
Material Properties: • Dry granulation: Improves flow and uniformity of materials with
poor flow • Direct compression: Requires materials with good flow and compressibility
from the start
Physical Properties of Tablets: • Dry granulation: Usually produces harder tablets, more
uniform weight • Direct compression: May have higher friability, content uniformity more
sensitive to segregation
Density of Materials: • Dry granulation: Increases bulk density of materials • Direct
compression: Uses original bulk density of materials
2.9 Write a note: Slugging(Dry granulation) and its applications.
Slugging is a dry granulation technique where powder blends are compressed into large,
flat compacts (slugs) without using liquid binders. These slugs are subsequently milled
and screened to produce granules for final tablet compression.
The process involves:
1. Initial blending of API with diluents and flow aids
2. Compression into large tablets (slugs) typically 1-2 inches in diameter
3. Size reduction of slugs using oscillating granulators or mills
4. Screening to obtain desired particle size distribution
5. Blending with lubricants and other external phase excipients
6. Final compression into tablets
Applications of slugging include: • Formulations containing moisture-sensitive drugs
where wet granulation is unsuitable • Heat-sensitive materials that could degrade during
drying processes • Processing of waxy or low-melting-point compounds that would
soften in conventional granulators • Small-scale production batches where investment
in roller compaction equipment is not justified • Development-stage formulation work
requiring minimal material consumption • Emergency productions when specialized
equipment is unavailable • Formulations with significant proportions of hydrophobic
materials • Drugs with poor flowability but reasonable compressibility • Production
environments with limited solvent handling capabilities • Handling cohesive powders
that are difficult to process by direct compression
Despite being less efficient than roller compaction, slugging remains valuable for
specialized applications and small-scale operations where simplicity and material
conservation are priorities.
2.10 Explain working principle of roller compactor with labelled diagram.
A roller compactor is a dry granulation device that compresses powder between two
counter-rotating rollers to form dense ribbons or sheets, which are subsequently milled
into granules.
Working principle: The process begins with feeding powder blend into the hopper. A feed
screw (auger) transports and pre-compacts the material toward the compression zone.
As the counter-rotating rollers receive the powder, they apply high pressure (typically 5-
10 MPa) in the nip region where the rollers are closest, consolidating the powder into a
solid ribbon or sheet. The compacted material exits the rollers and passes to a
mill/granulator where it's reduced to appropriate granule size, then screened to achieve
the desired particle size distribution.
Key components:
1. Feed hopper: Holds powder blend
2. Feed screw/auger: Transports and pre-compacts powder
3. Rollers: Apply compression force (smooth, knurled, or pocketed surface)
4. Hydraulic system: Controls roller pressure
5. De-aeration zone: Removes entrapped air from powder
6. Mill/granulator: Breaks compacted sheets into granules
7. Control system: Monitors and adjusts process parameters
Process variables that affect quality: • Roller pressure: Determines ribbon density and
strength • Roller speed: Impacts residence time and throughput • Feed screw speed:
Controls material delivery rate • Roller gap: Influences ribbon thickness • Roller surface
design: Affects ribbon characteristics and process efficiency
This method is ideal for moisture/heat-sensitive materials and offers consistent granule
properties with good control over critical quality attributes.
2.11 What is roller compactor? Draw label diagram, discuss its working and process
variable affecting on its performance.
A roller compactor is a dry granulation device that densifies powder mixtures by
compressing them between two counter-rotating rollers, producing solid sheets or
ribbons that are subsequently milled into granules of desired size.
Working principle: The process begins with the powder blend fed into the hopper. A
horizontal feed screw (auger) transports material to the vertical feed screw, which
delivers and pre-densifies the powder to the roller nip area. In the compression zone, the
counter-rotating rollers apply high pressure (5-10 MPa), consolidating the powder into
cohesive ribbons or sheets. These compacted materials are conveyed to an integrated
mill/granulator where they are reduced to appropriate granule size through controlled
size reduction. Finally, the granules are classified by screening to achieve the desired
particle size distribution.
Process variables affecting performance:
1. Roller pressure: Directly impacts ribbon density, hardness, and subsequent
granule properties. Higher pressures typically produce denser ribbons but may
cause over-compaction, reducing downstream compressibility.
2. Roller speed: Affects material residence time in the compression zone and
production capacity. Optimal speeds balance throughput with sufficient
compaction time.
3. Feed screw speed: Controls material delivery rate to rollers. Must maintain
appropriate ratio to roller speed for consistent ribbon formation.
4. Roller gap: Determines ribbon thickness and influences density. Narrower gaps
generally create denser ribbons.
5. Roller surface design: Smooth, knurled, or pocketed surfaces affect material
gripping and ribbon characteristics. Knurled surfaces improve powder grip but
create more irregular ribbons.
6. Feed material properties: Particle size, distribution, density, and compressibility
significantly impact process performance and final granule quality.
7. De-aeration capabilities: Efficiency of air removal affects ribbon porosity and
strength.
8. Milling parameters: Screen size, mill speed, and design influence final granule size
distribution and properties.
Proper control of these variables is essential for producing consistent granules with
desired flow and compaction characteristics.
2.12 Describe multistation rotary tablet compression cycle with diagram.
The multistation rotary tablet compression cycle occurs on a rotating turret containing
multiple tooling stations, each completing a full compression cycle per rotation. The
cycle involves:
1. Die filling: As the turret rotates, empty dies pass under the feed frame containing
powder/granules. The die cavity fills by gravity flow, assisted by feed paddles that
promote uniform filling.
2. Weight adjustment: Excess powder is scraped off by the feed frame, and the lower
punch position determines the fill volume and ultimate tablet weight.
3. Precompression: The upper and lower punches pass between the
precompression rollers, applying initial low pressure (10-30% of main
compression). This consolidates powder, removing entrapped air to prevent
capping and lamination.
4. Main compression: Punches pass between the main compression rollers, where
maximum pressure is applied. Upper punches are driven downward while lower
punches rise slightly, compressing the powder from both directions to form a
coherent tablet.
5. Ejection: After compression, the lower punch rises as it passes over the ejection
cam, pushing the tablet to the surface of the die.
6. Tablet removal: A sweep-off blade guides the tablet from the die to the discharge
chute.
7. Punch cleaning: The upper and lower punches pass over cleaning cams that
ensure proper alignment for the next cycle.
Throughout this process, the punches move vertically while following a circular path,
guided by cam tracks that precisely control their position at each stage. A complete cycle
takes just milliseconds, with production speeds of 5,000-1,000,000 tablets per hour
depending on machine size and formulation characteristics.
2.13 Explain components and cycle of rotary tablet compression machine.
Components of rotary tablet compression machine:
1. Turret: Rotating central component containing tooling stations (ranging from 8 to
80+), driven by main motor.
2. Tooling: Sets of upper and lower punches with corresponding dies that fit into the
turret.
3. Feed system: Consists of hopper and feed frame with paddles that distribute
powder evenly to dies.
4. Compression rollers: • Pre-compression rollers: Apply initial force to remove air •
Main compression rollers: Apply principal compaction force
5. Cam tracks: Guide the vertical movement of punches throughout rotation.
6. Ejection system: Includes ejection cam and take-off bar/sweep-off blade.
7. Drive system: Main motor, transmission, and controls for turret rotation.
8. Dust extraction system: Removes excess powder/dust during operation.
9. Control panel: Controls operational parameters and monitors compression
process.
10. Weight control system: Adjusts lower punch position to control fill volume and
tablet weight.
Tablet compression cycle:
1. Die filling: Empty die passes under feed frame, lower punch position determines
fill depth.
2. Weight adjustment: Excess powder removed by feed frame edges to ensure
uniform fill.
3. Precompression: Initial low pressure (10-30% of main force) consolidates powder,
removes air.
4. Main compression: Maximum pressure applied as punches pass between main
compression rollers, forming tablet.
5. Decompression: Pressure released gradually to allow elastic recovery without
damage.
6. Ejection: Lower punch rises, pushing tablet to die surface.
7. Discharge: Sweep-off blade transfers tablet from die to discharge chute.
8. Punch cleaning and realignment: Punches pass through cleaning section before
re-entering filling zone.
This continuous cycle occurs simultaneously at multiple stations during turret rotation,
producing thousands of tablets per minute.
2.14 Write a note on tablet tooling.
Tablet tooling consists of punches and dies that directly contact the powder blend during
compression, forming tablets of specific size, shape, and appearance. As critical
components of tablet production, tooling quality directly impacts tablet quality,
production efficiency, and press wear.
Standard tooling configurations include: • TSM/IPT (Tablet Specification Manual): Most
common in North America • EU (Eurostandard): Prevalent in Europe • BB (British
Standard): Used particularly in UK/Commonwealth
Tooling components:
1. Punches: Available as upper (longer) and lower (shorter) sets • Head: Interfaces
with compression rollers • Barrel: Main body providing strength and alignment •
Tip: Directly contacts formulation, defines tablet shape/embossing
2. Dies: Cylindrical pieces with precision-bored holes • Determines tablet diameter
• Precision-machined with tight tolerances
Common punch tip designs include: • Flat-faced: Simplest design • Flat-faced beveled
edge: Reduced edge stress • Concave: Standard cup depth • Deep concave: Greater cup
depth • Special shapes: Caplets, ovals, custom designs
Materials and manufacturing: • Tool steel (S7, D3) or tungsten carbide-tipped for wear
resistance • Manufactured to precise tolerances (±0.0005") • Surface treatments include
chrome plating, PVD coating
Maintenance considerations: • Regular inspection for wear/damage • Proper storage in
protective containers • Cleaning protocols to prevent residue buildup • Documentation
of usage history and reconditioning
Multi-tip tooling (containing 2+ tips per punch) increases productivity for small tablets
but requires more robust tablet presses.
2.15 Discuss in brief Pharmacopoeial tests for tablet.
Pharmacopoeial tests for tablets ensure consistent quality, safety, and efficacy through
standardized evaluations:
1. Weight Variation Test: Determines consistency of dosage units by weighing 20
tablets individually. For tablets ≥250mg, acceptable variation is ±5% from average
weight; for tablets <250mg, limits are ±7.5-10% depending on average weight.
2. Content Uniformity: Assesses drug distribution uniformity within and between
tablets. Ten individual units are assayed, with acceptance value (AV) ≤15 and no
individual content outside 75-125% of label claim.
3. Disintegration Test: Measures time for tablet breakdown in aqueous medium at
37±2°C. Standard tablets must disintegrate within 15 minutes, enteric-coated
tablets must resist disintegration in 0.1N HCl for 2 hours but disintegrate in
phosphate buffer.
4. Dissolution Test: Evaluates drug release rate in dissolution medium at 37±0.5°C
using specified apparatus (typically USP apparatus I/basket or II/paddle). For
immediate-release tablets, Q value (percentage dissolved) must meet specified
limits, usually Q=75-80% in 45 minutes.
5. Friability Test: Measures tablet resistance to mechanical stress. Sample of tablets
are weighed, rotated 100 times in friabilator, dedusted, and reweighed. Weight
loss should not exceed 1%.
6. Hardness Test: Determines tablet resistance to crushing. While not compendial,
typical acceptable range is 4-10 kg force.
7. Identification Tests: Confirm identity of active ingredient(s) through chemical or
spectroscopic methods.
8. Related Substances/Impurities: Limits specified impurities and degradation
products according to monograph specifications.
These standardized tests ensure consistent product quality across batches and
manufacturers.
2.16 Enlist official and unofficial tests for tablet evaluation. Explain any three in
detail.
Official (Pharmacopoeial) Tests:
1. Weight variation/Uniformity of weight
2. Content uniformity
3. Disintegration
4. Dissolution
5. Friability
6. Identification
7. Related substances/Impurities
Unofficial (Non-compendial) Tests:
1. Hardness/Breaking force
2. Thickness and diameter
3. Moisture content
4. Tablet porosity
5. Wetting time
6. Water absorption ratio
7. Stability testing
8. In-vitro bioequivalence
Detailed explanation of three tests:
1. Dissolution Test: Dissolution measures the rate and extent of drug release in an
aqueous medium simulating physiological conditions. The test is performed using
USP apparatus (typically basket or paddle) at 37±0.5°C with specified dissolution
medium. Samples are withdrawn at predetermined intervals and analyzed for
drug content. Acceptance criteria for immediate-release tablets typically require
Q=75-80% drug release within 30-60 minutes using a three-stage testing
approach. This test is critical as it correlates with in-vivo performance and serves
as a surrogate for bioavailability.
2. Content Uniformity: Content uniformity ensures consistent drug distribution
throughout a batch. Ten tablets are individually assayed for active ingredient
content. The test requires that the acceptance value (AV) calculated from the
results be ≤15, and no individual tablet should contain <75% or >125% of the
labeled content. The acceptance value incorporates both the deviation from
target content and the variability between units. This test is mandatory for low-
dose drugs and ensures therapeutic reliability.
3. Friability: Friability evaluates a tablet's resistance to mechanical stress during
handling, packaging, and shipping. A sample of pre-weighed tablets
(approximately 6.5g) is placed in a friabilator drum and rotated 100 times at 25
rpm. After testing, tablets are dedusted and reweighed. Weight loss should not
exceed 1% of the initial weight. Excessive friability indicates inadequate binding,
improper lubrication, or insufficient hardness that could compromise product
integrity and appearance during its lifecycle.
2.17 Describe dissolution test and its acceptance criteria for conventional release
tablets as per IP.
The dissolution test evaluates the rate and extent of drug release from tablet
formulations, serving as an in-vitro surrogate for bioavailability. For conventional
immediate-release tablets, Indian Pharmacopoeia (IP) specifies the following
methodology and acceptance criteria:
Test methodology:
1. Apparatus: Typically USP Apparatus II (paddle) at 50-75 rpm or Apparatus I
(basket) at 100 rpm, as specified in individual monographs.
2. Dissolution medium: 500-1000mL of specified buffer or aqueous solution
maintained at 37±0.5°C.
3. Sampling: Samples withdrawn at specified time points (typically 45 minutes for
immediate-release tablets).
4. Analysis: Samples analyzed using validated analytical methods (UV
spectrophotometry, HPLC) as specified in the monograph.
Acceptance criteria (staged testing approach): Stage 1 (S1): Test 6 units
• Each unit must dissolve to an extent ≥ Q+5%, where Q is the specified amount
(typically 75% or 80%) dissolved at the specified time.
• If all units meet this criterion, the product passes.
Stage 2 (S2): If S1 fails, test additional 6 units
• Average of 12 units (S1+S2) must be ≥ Q
• No unit is less than Q-15%
• If these criteria are met, the product passes.
Stage 3 (S3): If S2 fails, test additional 12 units
• Average of 24 units (S1+S2+S3) must be ≥ Q
• Not more than 2 units less than Q-15%
• No unit less than Q-25%
This staged approach balances stringent quality requirements with practical
manufacturing considerations, ensuring consistent drug release properties while
accounting for inherent variability in pharmaceutical production.
2.18 Differentiate: Disintegration and dissolution process.
Disintegration vs. Dissolution
Definition: • Disintegration: Physical process where tablet breaks into smaller particles
in aqueous medium • Dissolution: Physicochemical process where drug substance
dissolves from solid phase into solution
Test purpose: • Disintegration: Evaluates tablet's ability to break apart under
standardized conditions • Dissolution: Measures rate and extent of drug substance
release into solution
Correlation with bioavailability: • Disintegration: Limited correlation; passing test doesn't
ensure drug absorption • Dissolution: Strong correlation; typically better predictor of in
vivo performance
Test apparatus: • Disintegration: Glass tubes with mesh bottom in oscillating basket
assembly • Dissolution: USP apparatus I (basket), II (paddle), III (reciprocating cylinder),
or IV (flow-through cell)
Test conditions: • Disintegration: Water or specified medium at 37±2°C, no quantitative
analysis • Dissolution: Specific dissolution medium at 37±0.5°C with precise pH, volume,
and agitation rate
Testing time: • Disintegration: Typically 15-30 minutes for immediate-release tablets •
Dissolution: Variable timepoints (typically 30-60 minutes) with quantitative sampling
Acceptance criteria: • Disintegration: All tablets must disintegrate within specified time
(visual endpoint) • Dissolution: Specified percentage (Q value) must dissolve within
defined time, using staged testing approach
Regulatory significance: • Disintegration: Quality control test, may be waived if
dissolution specifications are established • Dissolution: Critical quality attribute,
required for release, stability, and sometimes biowaiver decisions
2.19 Discuss defects observed in tablet compression process.
Tablet compression defects arise from formulation issues, process parameters, or
equipment problems:
1. Capping: Separation of the upper segment of tablet • Causes: Air entrapment,
excessive fines, high punch speed, insufficient binding • Remedies:
Precompression stage, reduce turret speed, increase binder, reduce fines
2. Lamination: Horizontal splitting of tablets into layers • Causes: Air entrapment,
expansion of compressed air upon ejection, excessive lubricant • Remedies:
Precompression, reduce compression force, optimize lubricant level
3. Sticking: Adherence of formulation to punch faces • Causes: High moisture
content, insufficient lubricant, tacky materials • Remedies: Reduce moisture,
increase lubricant, modify punch surface finish
4. Picking: Small amount of material removed from tablet surface (especially where
embossing exists) • Causes: Punch surface imperfections, formulation stickiness
• Remedies: Polish punches, modify formulation, reduce embossing depth
5. Binding: Tablet edges are rough or "scuffed" • Causes: Excessive die wall friction,
inadequate lubrication • Remedies: Increase lubricant, polish dies, check punch-
die clearance
6. Mottling: Unequal distribution of color on tablet surface • Causes: Color
migration, inadequate mixing, API/excipient color differences • Remedies:
Change colorant, improve mixing, use color-matched excipients
7. Weight variation: Inconsistent tablet weights • Causes: Poor flow, uneven die
filling, worn machinery, segregation• Remedies: Improve flow with glidants, force
feeder adjustment, reduce vibration
8. Hardness issues: Tablets too soft or too hard • Causes: Compression force
variation, elastic recovery, lubricant level • Remedies: Optimize compression
force, binder adjustment, control lubricant
9. Double impression: Multiple debossing marks • Causes: Punch rotation during
compression or ejection • Remedies: Check turret timing, punch guide tolerance,
reduce press speed
10. Chipping: Edges breaking during ejection • Causes: Brittle formulation, excessive
pressure, deep concave punches • Remedies: Increase binder, reduce
compression force, modify punch design
Proper formulation development, process optimization, and equipment maintenance
can prevent these defects, ensuring consistent tablet quality.
2.20 Discuss the defects observed in tablet and its remedies.
Tablet defects arise from formulation issues, process parameters, or equipment
problems:
1. Capping and Lamination: • Defect: Tablet separates horizontally (cap) or splits
into layers • Causes: Air entrapment, excessive compression speed, poor
granulation, high moisture • Remedies: Implement precompression stage, reduce
turret speed, increase binder content, reduce fines, optimize moisture content
2. Sticking and Picking: • Defect: Material adheres to punch faces (sticking) or
creates pits on tablet surface (picking) • Causes: Insufficient lubrication, high
moisture, tacky materials • Remedies: Increase lubricant concentration, control
environmental humidity, modify formulation with less hygroscopic excipients,
polish punch surfaces
3. Weight Variation: • Defect: Inconsistent tablet weights beyond acceptance limits
• Causes: Poor powder flow, uneven die filling, segregation, worn equipment •
Remedies: Add glidants, optimize particle size distribution, adjust feed frame
settings, check/replace worn parts
4. Friability Issues: • Defect: Tablets chip, abrade, or break during handling • Causes:
Insufficient binder, low compression force, poor granulation • Remedies: Increase
binder concentration, optimize compression force, improve granulation
technique
5. Hardness Problems: • Defect: Tablets too soft or too hard • Causes: Compression
force variation, formulation issues, lubricant level • Remedies: Standardize
compression force, adjust binder content, control lubricant level
6. Mottling: • Defect: Uneven color distribution on tablet surface • Causes:
Chemical incompatibilities, API/excipient color differences, migration during
drying • Remedies: Use color-matched excipients, improve blending, reformulate
with different colorants
7. Content Uniformity Failure: • Defect: Variable drug content among tablets •
Causes: Poor mixing, segregation, wide particle size distribution • Remedies:
Optimize mixing parameters, reduce particle size differences, consider wet
granulation
8. Dissolution Failure: • Defect: Insufficient drug release within specified time •
Causes: Excessive compression force, poor disintegration, hydrophobic
excipients • Remedies: Adjust compression force, increase disintegrant level,
reconsider excipient selection
Preventing these defects requires systematic formulation development, process
optimization, equipment maintenance, and robust quality control.
2.21 Describe the compression processing defects in tablet and give its remedies.
Compression processing defects in tablets result from issues during the compression
stage of manufacturing:
1. Capping: • Description: The top or bottom crown separates from the main body of
the tablet • Causes: Air entrapment during compression, excessive punch speed,
expansion of elastic materials • Remedies: Implement precompression step,
reduce turret speed, optimize moisture content (1-2%), increase binder
concentration, reduce fines content
2. Lamination: • Description: Separation of the tablet into horizontal layers •
Causes: Air entrapment between granules, excessive magnesium stearate,
stratified powder bed • Remedies: Reduce compression force, optimize lubricant
concentration, ensure uniform granule density, improve granulation process
3. Sticking: • Description: Formulation adheres to punch faces during compression
• Causes: Insufficient lubrication, high moisture content, tacky materials •
Remedies: Increase lubricant level, reduce moisture content, polish punch
surfaces, adjust formulation with less hygroscopic materials
4. Picking: • Description: Small amounts of material pulled from tablet surface, often
in embossed areas • Causes: Punch surface imperfections, insufficient binding,
adhesive formulation • Remedies: Polish or replace punches, increase binder
concentration, simplify embossing design
5. Binding in die: • Description: Tablets stick to die wall during ejection causing rough
edges • Causes: Insufficient lubrication, excessive die wall friction, rough die
surface • Remedies: Increase lubricant, polish die walls, check punch-to-die
clearance, check for worn dies
6. Double impression: • Description: Multiple impressions or debossing marks on
tablets • Causes: Tablet rotation during ejection, loose punch guides • Remedies:
Check turret timing, adjust ejection cam, verify proper punch guide tolerance
7. Weight variation: • Description: Inconsistent tablet weights • Causes: Poor
powder flow, uneven die filling, worn feeder components • Remedies: Add flow
enhancers, adjust fill depth, check feed frame components for wear, reduce
vibration
8. Hardness fluctuation: • Description: Variable tablet hardness within batch •
Causes: Inconsistent compression force, variable powder density • Remedies:
Check and calibrate compression force control, improve powder uniformity, verify
force feedback system
Addressing these defects requires systematic investigation of formulation properties,
process parameters, and equipment condition to implement appropriate corrective
measures.
2.22 Discuss different film coating defects.
Film coating defects can compromise tablet appearance, stability, and functionality:
1. Orange Peel Effect: • Appearance: Rough, uneven surface resembling orange peel
• Causes: Excessive spray rate, improper atomization pressure, inadequate
droplet formation • Remedies: Reduce spray rate, optimize atomization pressure,
adjust viscosity of coating solution
2. Picking/Sticking: • Appearance: Surface imperfections from tablets sticking
together or to equipment • Causes: Overwetting, insufficient drying, excessive
tablet bed moisture • Remedies: Reduce spray rate, increase drying air
temperature/volume, adjust tablet bed movement
3. Coating Erosion: • Appearance: Partial removal of coating during process •
Causes: Excessive tablet-to-tablet or tablet-to-pan attrition, inadequate film
formation • Remedies: Reduce pan speed, optimize tablet load, increase
plasticizer content
4. Cracking/Splitting: • Appearance: Visible cracks in film coating • Causes:
Insufficient plasticizer, rapid drying conditions, film-tablet core expansion
differences • Remedies: Increase plasticizer concentration, reduce drying
temperature, modify coating formulation
5. Peeling/Flaking: • Appearance: Film separates from tablet surface • Causes: Poor
adhesion, tablet surface contamination, incompatible subcoat • Remedies:
Improve tablet surface cleanliness, add adhesion promoter, implement
appropriate subcoating
6. Blistering: • Appearance: Bubbles or blisters in coating • Causes: Entrapped
air/moisture expanding during heating, solvent entrapment • Remedies: Modify
heating profile, reduce spray rate, adjust coating solution composition
7. Bridging of Logo/Breaking Line: • Appearance: Filling in of embossed details •
Causes: Excessive coating thickness, improper atomization, inadequate pan
speed • Remedies: Reduce total coating applied, optimize spray pattern, increase
pan speed, adjust spray gun distance
8. Color Variation: • Appearance: Uneven color distribution across tablets • Causes:
Segregation of colorants, inconsistent spray pattern, improper mixing • Remedies:
Improve coating suspension uniformity, optimize spray gun positioning, ensure
adequate tablet bed mixing
9. Twinning: • Appearance: Two or more tablets stuck together • Causes:
Overwetting, insufficient separation of tablets in pan • Remedies: Reduce spray
rate, increase pan speed, optimize tablet load
10. Edge Wear/Chipping: • Appearance: Coating damage at tablet edges • Causes:
Excessive attrition, insufficient coating strength, brittle coating • Remedies:
Increase plasticizer, reduce pan speed, modify tablet design to reduce edge
sharpness
Preventing these defects requires careful optimization of coating formulation, process
parameters, and equipment configuration.
2.23 Describe the coating defects in tablet and give its remedies.
Tablet coating defects can significantly impact product quality, appearance, and
performance:
1. Orange Peel Effect: • Description: Rough, textured surface resembling orange peel
• Causes: Premature droplet evaporation, excessive spray rate, improper
atomization • Remedies: Lower inlet air temperature, reduce spray rate, optimize
atomization pressure, adjust coating solution viscosity
2. Picking/Sticking: • Description: Areas where coating is removed due to tablets
sticking together • Causes: Overwetting, insufficient drying, tackiness of coating
material • Remedies: Reduce spray rate, increase drying efficiency, adjust pan
speed, add anti-tacking agents
3. Bridging of Logos/Scoring: • Description: Coating fills embossed areas or score
lines • Causes: Excessive coating thickness, improper atomization, tablet design
issues • Remedies: Reduce coating application, optimize spray parameters,
modify embossing depth
4. Color Variation: • Description: Inconsistent color across tablet surface or
between tablets • Causes: Inadequate mixing of coating suspension, improper
spray pattern, segregation of colorants • Remedies: Improve suspension
homogeneity, optimize spray gun positions, ensure proper agitation
5. Cracking/Splitting: • Description: Visible cracks in coating film • Causes:
Insufficient plasticizer, tablet core expansion, rapid drying conditions • Remedies:
Increase plasticizer concentration, adjust drying parameters, modify coating
formulation flexibility
6. Peeling/Flaking: • Description: Coating separates from tablet core • Causes: Poor
adhesion, core surface contamination, incompatible subcoat • Remedies: Ensure
clean tablet surfaces, add adhesion promoters, implement appropriate
subcoating
7. Blistering: • Description: Bubble-like formations in coating layer • Causes:
Entrapped air/moisture expanding during drying, solvent entrapment • Remedies:
Optimize drying profile, adjust spray rate, ensure complete drying between
coating layers
8. Edge Wear/Chipping: • Description: Coating erosion at tablet edges • Causes:
Excessive tablet-to-tablet attrition, insufficient coating strength • Remedies:
Reduce pan speed, increase coating flexibility with plasticizers, modify tablet
design
9. Dulling: • Description: Loss of coating gloss • Causes: Improper drying conditions,
moisture absorption, plasticizer migration • Remedies: Optimize drying
parameters, adjust plasticizer type/concentration, control storage conditions
10. Twinning: • Description: Tablets adhering together during coating • Causes:
Excessive spray rate, inadequate tablet bed movement • Remedies: Reduce spray
rate, optimize pan load, increase pan speed
Preventing these defects requires systematic control of formulation parameters, process
conditions, and equipment variables throughout the coating operation.
2.24 Give the reasons for enteric coating of tablet. Enlist enteric and non enteric film
former materials. Write note on plasticizer.
Reasons for enteric coating of tablets:
1. Protection of acid-sensitive drugs from gastric degradation (e.g., enzymes,
probiotics)
2. Prevention of gastric irritation from certain drugs (e.g., aspirin, NSAIDs)
3. Targeted drug delivery to the intestinal tract for local action
4. Delayed release for pulsatile drug delivery systems
5. Protection of gastric mucosa from irritating drugs
6. Masking unpleasant taste or odor without immediate dissolution in mouth
Enteric film-forming materials: • Cellulose acetate phthalate (CAP) • Hydroxypropyl
methylcellulose phthalate (HPMCP) • Methacrylic acid copolymers (Eudragit L, S series)
• Polyvinyl acetate phthalate (PVAP) • Shellac • Cellulose acetate trimellitate (CAT) •
Shellac • Sodium alginate
Non-enteric film-forming materials: • Hydroxypropyl methylcellulose (HPMC) •
Methylcellulose (MC) • Ethylcellulose (EC) • Polyvinyl alcohol (PVA) • Hydroxypropyl
cellulose (HPC) • Methacrylic acid copolymers (Eudragit E, RL, RS series) •
Polyvinylpyrrolidone (PVP) • Sodium carboxymethylcellulose (Na-CMC)
Plasticizers: Plasticizers are essential additives in film coating formulations that enhance
the physical properties of polymeric films. They work by positioning themselves between
polymer chains, reducing intermolecular forces and increasing chain mobility. This
results in more flexible, less brittle films with lower glass transition temperatures.
Key functions of plasticizers include: • Reducing film brittleness and preventing
cracking/flaking • Lowering the minimum film formation temperature • Improving film
adhesion to tablet surface • Enhancing film elasticity and stress resistance • Reducing
residual stresses within films during drying
Common plasticizers include: • Polyethylene glycols (PEG 400, 6000) • Propylene glycol
• Glycerin • Dibutyl sebacate • Triethyl citrate • Acetylated monoglycerides • Diethyl
phthalate (less common now due to safety concerns)
Plasticizer concentration typically ranges from 10-30% of the polymer weight, with
selection based on compatibility with the film former, desired mechanical properties,
and stability considerations.
2.25 Discuss advantages and formulation of film coating for tablets.
Advantages of film coating:
1. Process efficiency: Significantly shorter process time compared to sugar coating
(2-3 hours vs. days)
2. Weight gain economy: Minimal weight increase (2-3% vs. 50-100% for sugar
coating)
3. Mechanical strength: Minimal impact on tablet hardness and friability
4. Process flexibility: Adaptable to various tablet shapes and embossing designs
5. Functional modifications: Can incorporate modified release properties (enteric,
extended release)
6. Stability enhancement: Protection from light, moisture, and environmental
factors
7. Identity preservation: Maintains tablet identification features and score lines
8. Taste/odor masking: Effective barrier for unpleasant organoleptic properties
9. Improved appearance: Elegant, uniform surface with color options
10. Automation compatibility: Suitable for high-speed packaging operations
Film coating formulation components:
1. Film formers (40-65%): • Cellulosic polymers: HPMC, HPC, EC • Acrylic polymers:
Eudragit® series • Vinyl polymers: PVP, PVA • Selection based on desired release
profile, solubility, and coating method
2. Plasticizers (5-30% of polymer weight): • Purpose: Reduce brittleness, lower glass
transition temperature • Examples: PEG, propylene glycol, triacetin, citrate esters
• Selection based on compatibility with film former
3. Solvents/Vehicles (30-80%): • Aqueous systems: Water-based dispersions
(environmentally preferred) • Organic solvents: Alcohols, ketones (faster drying
but environmental/safety concerns) • Selection impacts drying efficiency,
sustainability, and safety
4. Colorants (0.1-2%): • Water-soluble dyes: FD&C, D&C colors • Pigments: Iron
oxides, titanium dioxide, aluminum lakes • Selection based on stability and
regulatory status
5. Other additives: • Opacifiers: Titanium dioxide for light protection •
Sweeteners/flavors: For chewable tablets • Surfactants: Improve spreading and
wetting • Antimicrobial preservatives: For aqueous systems
The formulation is typically prepared as a solution or suspension with 8-15% solids
content and applied using perforated pan coaters or fluid bed equipment under
controlled temperature and airflow conditions.
2.26 Explain following terms and remedies to prevent it: 1. Orange peel effect 2.
Mottling 3. Cracking 4. Chipping 5. Lamination
1. Orange Peel Effect: • Description: Rough, textured coating surface resembling
orange peel • Causes: Premature droplet evaporation before adequate spreading,
high spray rate, improper atomization, excessive inlet air temperature • Remedies:
Reduce inlet air temperature (5-10°C reduction), decrease spray distance,
increase atomization pressure, reduce coating solution viscosity, adjust spray rate
downward, add appropriate plasticizer
2. Mottling: • Description: Uneven color distribution creating light and dark areas on
tablet surface • Causes: Migration of soluble dyes with drying front, drug/excipient
color bleeding through coating, color incompatibility with tablet components •
Remedies: Use pigments instead of dyes, increase coating thickness, formulate
with opacifiers (TiO2), implement subcoating layer, ensure uniform spray pattern
and drying, modify core formulation to reduce migrating components
3. Cracking: • Description: Visible fractures in the coating film • Causes: Insufficient
plasticizer, internal stresses during drying, thermal expansion differences
between core and coating, brittle film formation • Remedies: Increase plasticizer
concentration (5-10% additional), reduce drying temperature, implement gradual
cooling process, select more flexible polymer system, decrease coating thickness
per pass, modify curing conditions
4. Chipping: • Description: Pieces of coating breaking off, particularly at tablet edges
• Causes: Poor coating adhesion, excessive tablet attrition in pan, insufficient
coating strength, sharp tablet edges • Remedies: Increase coating flexibility with
appropriate plasticizer, reduce pan speed, optimize tablet load, modify tablet
tooling for rounded edges, improve tablet core integrity, adjust pan baffles to
reduce tablet impact
5. Lamination: • Description: Separation of tablet into horizontal layers after
compression • Causes: Air entrapment during compression, excessive fines,
improper granulation, high compression speed, elastic recovery • Remedies:
Implement precompression step, reduce turret speed, optimize granulation
process to reduce fines, modify formula with better binders, adjust compression
force, ensure adequate dwell time, control granule density
Each of these defects can significantly impact product quality and performance,
necessitating careful optimization of formulation components, process parameters, and
equipment settings to prevent their occurrence.
2.27 Comment: Eudragit E is an enteric coating polymer.
The statement "Eudragit E is an enteric coating polymer" is incorrect.
Eudragit E (specifically Eudragit E PO/E 100) is a cationic copolymer based on
dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate. It has
properties directly opposite to enteric coating polymers:
1. Solubility profile: Eudragit E is soluble in gastric fluid up to pH 5.0 but insoluble in
intestinal environment above pH 5.5. This is contrary to enteric polymers, which
are insoluble in acidic pH but dissolve at higher intestinal pH.
2. Functional application: Eudragit E is used for immediate release formulations in
the stomach, taste masking, and moisture protection. It dissolves rapidly in the
stomach, releasing drug promptly.
3. Chemical nature: As a cationic polymer, it contains dimethylaminoethyl
functional groups that become protonated and soluble in acidic conditions. True
enteric polymers typically contain carboxylic acid groups that remain unionized
(insoluble) at low pH.
Enteric coating polymers include Eudragit L and S series, cellulose acetate phthalate,
and HPMC phthalate, which remain intact in acidic gastric conditions but dissolve in the
higher pH of the intestine.
Eudragit E is therefore classified as a protective or functional coating polymer for
immediate gastric release, not an enteric coating material.
2.28 Write a short note on Fluidized bed coater.
A fluidized bed coater is an advanced pharmaceutical equipment that combines several
unit operations (mixing, granulation, drying, and coating) in a single system. It utilizes the
principle of air suspension, where upward-flowing air suspends solid particles in a
controlled fluidized state while coating solution is sprayed onto the particles.
Key components: • Product container with air distribution plate • Expansion chamber
with filters • Spray system (nozzles and pump) • Air handling unit (heater, blower, filters)
• Control systems for temperature, airflow, spray rate • Collection systems for exhausted
air
Configuration types:
1. Top-spray: Spray nozzle positioned above the fluidized bed, most commonly used
for granulation
2. Bottom-spray (Wurster process): Nozzle positioned at bottom with cylindrical
partition creating organized particle flow, ideal for uniform coating
3. Tangential-spray: Rotating disk at bottom creating centrifugal force combined
with fluidization, suitable for both granulation and coating
Advantages: • All-in-one processing (drying and coating in same equipment) • Excellent
heat and mass transfer efficiency • Uniform coating distribution • Shorter processing
times compared to pan coating • Suitable for coating smaller particles (pellets, granules,
mini-tablets) • Automated process control capabilities • Closed system reducing
contamination risk
Process parameters requiring optimization: • Inlet/outlet air temperature • Air flow rate •
Spray rate and atomization pressure • Solution concentration and viscosity • Nozzle
position and design • Processing time
Applications include film coating of multiparticulates, taste masking, modified release
coating, granulation, and pellet manufacturing, making it versatile equipment for modern
pharmaceutical production.