Tablets
UNIT III
V.MANIMARAN
LECTURER
DEPARTMENT OF PHARMACEUTICS
SRM COLLEGE OF PHARMACY
Introduction
Solid medicaments may be administered orally as powders, pills, cachets, capsules
or tablets .These dosage forms contain a quantity of drug which is given as a single
unit and they are known collectively as solid unit dosage forms, even in the case of
sustained action preparations which, technically, contain the equivalent of several
normal doses of drug .The stringent formulation requirements of modern
medicaments, the many advantages of tablet and capsule medication, coupled
with expanding health services and the commitment need for large‐scale
economic manufacture, have led to a steady decline in the prescribing of powders
and pills .Tablets and capsules, on the other hand, currently account for well over
two third of the total number and cost of medicines produced all over the world.
Tablet is defined as a compressed solid dosage form containing medicaments with
or without excipients. According to the Indian Pharmacopoeia Pharmaceutical
tablets are solid, flat or biconvex dishes, unit dosage form, prepared by
compressing a drugs or a mixture of drugs, with or without diluents. They vary in
shape and differ greatly in size and weight, depending on amount of medicinal
substances and the intended mode of administration. It is the most popular
dosage form and 70% of the total medicines are dispensed in the form of Tablet.
All medicaments are available in the Tablet form except where it is difficult to
formulate or administer.
The advantages of the Tablet dosage form are:
1. They are unit dosage form and offer the greatest capabilities of all oral dosage form
for the greatest dose precision and the least content variability.
2. Cost is lowest of all oral dosage form.
3. Lighter and compact.
4. Easiest and cheapest to package and strip.
5. Easy to swallowing with least tendency for hang‐up.
6. Sustained release product is possible by enteric coating.
7. Objectionable odour and bitter taste can be masked by coating technique.
8. Suitable for large scale production.
9. Greatest chemical and microbial stability over all oral dosage form.
10. Product identification is easy and rapid requiring no additional steps when
employing an embossed and/or monogrammed punch face.
Disadvantages of Tablet dosage form are:
1. Difficult to swallow in case of children and unconscious patients.
2. Some drugs resist compression into dense compacts, owing to amorphous nature,
low density character.
3. Drugs with poor wetting, slow dissolution properties, optimum absorption high in GIT
may be difficult to formulate or manufacture as a tablet that will still provide adequate or
full drug bioavailability.
4. Bitter testing drugs, drugs with an objectionable odor or drugs that are sensitive to
oxygen may require encapsulation or coating. In such cases, capsule may offer the best
and lowest cost.
2
General properties of Tablet dosage forms:
1. A tablet should have elegant product identity while free of defects like chips, cracks,
discoloration, and contamination.
2. Should have sufficient strength to withstand mechanical shock during its
production packaging, shipping and dispensing.
3. Should have the chemical and physical stability to maintain its physical attributes
over time
4. The tablet must be able to release the medicinal agents in a predictable and
reproducible manner.
5. Must have a chemical stability over time so as not to follow alteration of the
medicinal agents.
Different types of Tablets
(A) Tablets ingested orally:
1. Compressed tablet, e.g. Paracetamol tablet
2. Multiple compressed tablet
3. Repeat action tablet
4. Delayed release tablet, e.g. Enteric coated Bisacodyl tablet
5. Sugar coated tablet, e.g. Multivitamin tablet
6. Film coated tablet, e.g. Metronidazole tablet
7. Chewable tablet, e.g. Antacid tablet
(B) Tablets used in oral cavity:
1. Buccal tablet, e.g. Vitamin‐c tablet
2. Sublingual tablet, e.g. Vicks Menthol tablet
3. Troches or lozenges
4. Dental cone
(c) Tablets administered by other route:
1. Implantation tablet
2. Vaginal tablet, e.g. Clotrimazole tablet
(D) Tablets used to prepare solution:
1. Effervescent tablet, e.g. Dispirin tablet (Aspirin)
2. Dispensing tablet, e.g. Enzyme tablet (Digiplex)
3. Hypodermic tablet
4. Tablet triturates e.g. Enzyme tablet (Digiplex)
Tablet Ingredients
In addition to active ingredients, tablet contains a number of inert materials known
as additives or excipients. Different excipients are:
1. Diluent
2. Binder and adhesive
3. Disintegrents
4. Lubricants and glidants
5. Colouring agents
6. Flavoring agents
7. Sweetening agents
1. Diluent: Diluents are fillers used to make required bulk of the tablet when the drug
dosage itself is inadequate to produce the bulk. Secondary reason is to provide better
tablet properties such as improve cohesion, to permit use of direct compression
manufacturing or to promote flow. A diluent should have following properties:
1. They must be non toxic
2. They must be commercially available in acceptable grade
3. There cost must be low
4. They must be physiologically inert
5. They must be physically & chemically stable by themselves & in combination
with the drugs.
6. They must be free from all microbial contamination.
7. They do not alter the bioavailability of drug.
8. They must be color compatible.
Commonly used tablet diluents
1. Lactose‐anhydrous and spray dried lactose
2. Directly compressed starch‐Sta Rx 1500
3. Hydrolyzed starch‐Emdex and Celutab
4. Microcrystalline cellulose‐Avicel (PH 101and PH 102)
5. Dibasic calcium phosphate dehydrate
6. Calcium sulphate dihydrate
7. Mannitol
8. Sorbitol
9. Sucrose‐ Sugartab, DiPac, Nutab
10. Dextrose
2. Binders and Adhesives: These materials are added either dry or in wet‐
form to form granules or to form cohesive compacts for directly compressed
tablet.
Example: Acacia, tragacanth‐ Solution for 10‐25% Conc.
Cellulose derivatives‐Methyl cellulose, Hydroxy propyl methyl
cellulose, Hydroxy propyl cellulose
Gelatin‐ 10‐20% solution
Glucose‐ 50% solution
Polyvinylpyrrolidone (PVP)‐ 2% conc.
Starch paste‐10‐20% solution
Sodium alginate
Sorbitol
3. Disintegrants: Added to a tablet formulation to facilitate its breaking or
disintegration when it contact in water in the GIT.
Example: Starch‐ 5‐20% of tablet weight.
Starch derivative – Primogel and Explotab (1‐8%)
Clays‐ Veegum HV, bentonite 10% level in colored tablet only
Cellulose
Cellulose derivatives‐ Ac‐ Di‐Sol (sodium carboxy methyl
cellulose)
Alginate
PVP (Polyvinylpyrrolidone), cross‐linked
Superdisintegrants: Swells up to ten fold within 30 seconds when contact
water.
Example: Crosscarmellose‐ cross‐linked cellulose, Crosspovidone‐ cross‐linked
povidone (polymer), Sodium starch glycolate‐ cross‐linked starch. These cross‐
linked products swell upto 10n fold with in 30 seconds when in contact with water.
A portion of disintegrant is added before granulation and a portion before
compression, which serve as glidants or lubricant. Evaluation of carbon dioxide
in effervescent tablets is also oneway of disintegration
4. Lubricant and Glidants: Lubricants are intended to prevent adhesion of
the tablet materials to the surface of dies and punches, reduce inter particle
friction andmay improve the rate of flow of the tablet granulation.
Glidants are intended to promote flow of granules or powder material by reducing
the friction between the particles.
Example: Lubricants‐ Stearic acid, Stearic acid salt ‐ Stearic acid, Magnesium
stearate, Talc, PEG (Polyethylene glycols), Surfactants
Glidants‐ Corn Starch – 5‐10% conc., Talc‐5% conc., Silica derivative ‐ Colloidal
silicas such as Cab‐O‐Sil, Syloid, Aerosil in 0.25‐3% conc.
5. Coloring agent: The use of colors and dyes in a tablet has three purposes:
(1) Masking of off color drugs
(2) Product Identification
(3) Production of more elegant product
All coloring agents must be approved and certified by FDA. Two forms of colors are
used in tablet preparation – FD &C and D & C dyes. These dyes are applied as
solution in the granulating agent or Lake form of these dyes. Lakes are dyes absorbed
on hydrous oxide and employed as dry powder coloring.
Example: FD & C yellow 6‐sunset yellow
FD & C yellow 5‐ Tartrazine
FD & C green 3‐ Fast Green
FD & C blue 1‐ Brilliant Blue
FD & C blue 2 ‐ Indigo carmine
D & C red 3‐ Erythrosine.
D & C red 22 – Eosin Y
6. Flavoring agents: For chewable tablet‐ flavor oil are used
7. Sweetening agents: For chewable tablets: Sugar, mannitol.
Saccharine (artificial): 500 time’s sweeter than sucrose
Disadvantage: Bitter aftertaste and carcinogenic
Aspartame (artificial)
Disadvantage: Lack of stability in presence of moisture.
Granulation technology on large scale by various techniques
Tablet Compression Machine
Tablets are made by compressing a formulation containing a drug or drugs with
excipients on stamping machine called presses. Tablet presses are designed with
following basic components:
1) Hopper for holding and feeding granulation
2) Dies that define the size and shape of the tablet.
3) Punches for compressing the granulation within the dies.
4) Cam tracks for guiding the movement of the punches.
5) A feeding mechanism for moving granulation from hopper into the
dies
Evaluation of Tablet
1. General Appearance: The general appearance of a tablet, its identity and
general elegance is essential for consumer acceptance, for control of lot‐to‐lot
uniformity and tablet‐to‐tablet uniformity. The control of general appearance
involves the measurement of size, shape, color, presence or absence of odor, taste
etc.
2. Size & Shape: It can be dimensionally described & controlled. The thickness of
a tablet is only variables. Tablet thickness can be measured by micrometer or by
other device. Tablet thickness should be controlled within a ± 5% variation of
standard value.
3. Unique identification marking: These marking utilize some form of
embossing, engraving or printing. These markings include company name or
symbol, product code, product name etc.
4. Organoleptic properties: Color distribution must be uniform with no
mottling. For visual color comparison compare the color of sample against
standard color.
5. Hardness and Friability: Tablet requires a certain amount of strength or
hardness and resistance to friability to withstand mechanical shakes of handling
in manufacture, packaging and shipping. Hardness generally measures the tablet
crushing strength
6.Friability: Friability of a tablet can determine in laboratory by Roche friabilator.
This consist of a plastic chamber that revolves at 25 rpm, dropping the tablets
through a Distance of six inches in the friabilator, which is then operate for 100
revolutions. The tablets are reweighed. Compress tablet that lose less than 0.5 to 1.0
% of the Tablet weigh are consider acceptable.
2. Drug Content and Release:
(I) Weight Variation test (U.S.P.): Take 20 tablet and weighed individually. Calculate
average weight and compare the individual tablet weight to the average. The tablet pass the
U.S.P. test if no more that 2 tablets are outside the percentage limit and if no tablet differs by
more than 2 times the percentage limit.
(II) Content Uniformity Test: Randomly select 30 tablets. 10 of these assayed individually.
The Tablet pass the test if 9 of the 10 tablets must contain not less than 85% and not more than
115% of the labeled drug content and the 10th tablet may not contain less than 75% and more
than 125% of the labeled content. If these conditions are not met, remaining 20 tablet assayed
individually and none may fall out side of the 85 to 115% range.
(III) Disintegration Test (U.S.P.): The U.S.P. device to test disintegration uses 6 glass
tubes that are 3” long; open at the top and 10 mesh screen at the bottom end. To test for
disintegration time, one tablet is placed in each tube and the basket rack is positioned in a 1‐L
beaker of water, simulated gastric fluid or simulated intestinal fluid at 37 ± 20 C such that the
tablet remain 2.5 cm below the surface of liquid on their upward movement and not closer than
2.5 cm from the bottom of the beaker in their downward movement. Move the basket
containing the tablets up and down through a distance of 5‐6 cm at a frequency of 28 to 32
cycles per minute. Floating of the tablets can be prevented by placing perforated plastic discs on
each tablet.
According to the test the tablet must disintegrate and all particles must pass through the 10
mesh screen in the time specified. If any residue remains, it must have a soft mass.
Disintegration time: Uncoated tablet: 5‐30 minutes
Coated tablet: 1‐2 hours
3.Dissolution Test (U.S.P.): Two set of apparatus:
Apparatus‐1: A single tablet is placed in a small wire mesh basket attached to the
bottom of the shaft connected to a variable speed motor. The basket is immersed in
a dissolution medium (as specified in monograph) contained in a 100 ml flask. The
flask is cylindrical with a hemispherical bottom. The flask is maintained at
37±0.50C by a constant temperature bath. The motor is adjusted to turn at the
specified speed and sample of the fluid are withdrawn at intervals to determine the
amount of drug in solutions.
Apparatus‐2: It is same as apparatus‐1, except the basket is replaced by a paddle.
The dosage form is allowed to sink to the bottom of the flask before stirring. For
dissolution test U.S.P. specifies the dissolution test medium and volume, type of
apparatus to be used, rpm of the shaft, time limit of the test and assay procedure
for. The test tolerance is expressed as a % of the labeled amount of drug dissolved in
the time limit.
Tablet Coating
Tablet coatings perform one or more of the following functions. They may: mask the taste
of unpalatable drugs, protect the drug from deterioration due to light, oxygen or moisture,
separate incompatible ingredients, control the release of medicament in the
gastrointestinal tract, and provide an elegant or distinctive finish to the tablet.
The materials used for coating may largely comprise sucrose (sugar coating), water‐soluble
film‐forming polymers (film coating) or substances which are soluble in the intestinal
secretions but not in those of the stomach (enteric coating). These types of coating can all
be applied by the pan or fluid‐bed processes; the compression coating technique is suitable
for sugar and enteric coatings, but not for film coating.
Types of Coating
Different coating processes are: Pan coating, Fluid Bed Coating, Compression coating
A. Pan Coating
B. Fluid‐Bed Coating
Compression Coating Machines
Other methods of coating equipments:
Perforated Pan Systems
Accela‐Cota: It is a prototype of perforated cylindrical drum providing high
drying air capacity. Therefofe it is preferred for film coating.
Hi‐coater system: The drying air is directed into the drum is passed through the
tablet bed, and is exhausted through the perforations in the drum.
SUPERCELL™ Tablet Coater
Revolutionary tablet coater that accurately deposits controlled amounts of coating
materials on tablets, even if they are extremely hygroscopic or friable.
Problems in tableting
1 Capping
2 Lamination / Laminating
3 Chipping
4 Cracking
5 Sticking / Filming
6 Picking
7 Binding
8 Mottling
9 Double impression
Problems and remedies for tablet coating
1 Blistering
2 Chipping
3 Cratering
4 Picking
5 Pitting
6 Blooming
7 Blushing
8 Colour variation
9 Infilling
10 Orange peel/Roughness
11 Cracking/Splitting
THE CAUSES AND REMEDIES OF CAPPING RELATED TO ‘FORMULATION’ (GRANULATION)
Sr. No. CAUSES REMEDIES
Remove some or all fines through 100
1. Large amount of fines in the granulation
to 200 mesh screen
Moisten the granules suitably. Add
Too dry or very low moisture content
2. hygroscopic substance e.g.: sorbitol,
(leading to loss of proper binding action).
methyl‐ cellulose or PEG‐4000
3. Not thoroughly dried granules. Dry the granules properly.
Increasing the mount of binder OR
Adding dry binder such as pre‐
Insufficient amount of binder or improper
4. gelatinized starch, gum acacia,
binder.
powdered sorbitol, PVP, hydrophilic
silica or powdered sugar.
Increase the amount of lubricant or
5. Insufficient or improper lubricant.
change the type of lubricant.
6. Granular mass too cold to compress firm. Compress at room temperature.
THE CAUSES AND REMEDIES OF CAPPING RELATED TO ‘MACHINE’ (DIES, PUNCHES AND TABLET PRESS)
Sr. No. CAUSES REMEDIES
Polish dies properly. Investigate
1.
Poorly finished dies other steels or other materials.
Deep concave punches or Deep concave punches or
2.
beveled‐edge faces of punches. beveled‐edge faces of punches.
Lower punch remains below the Make proper setting of lower
3.
face of die during ejection. punch during ejection.
Incorrect adjustment of sweep‐off Adjust sweep‐off blade correctly
4.
blade. to facilitate proper ejection.
Reduce speed of turret (Increase
5. High turret speed.
dwell time).
The Causes and Remedies of Lamination related to MACHINE (Dies, Punches and Tablet Press)]
Sr. No. CAUSES REMEDIES
1. Rapid relaxation of the peripheral regions of a tablet, Use tapered dies, i.e. upper part of the die bore has an
on ejection from a die. outward taper of 3° to 5°.
2 Rapid decompression Reduce turret speed and reduce the final compression
Use pre‐compression step. pressure.
THE CAUSES AND REMEDIES OF CHIPPING RELATED TO FORMULATION (GRANULATION) ARE AS FOLLOWS
CAUSES REMEDIES
Sr. No.
1. Sticking on punch faces Dry the granules properly or increase lubrication.
2. Too dry granules. Moisten the granules to plasticize. Add hygroscopic substances.
3. Too much binding causes chipping at bottom. Optimize binding, or use dry binders.
THE CAUSES AND REMEDIES OF CHIPPING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
Sr. No. CAUSES REMEDIES
1. Groove of die worn at compression point. Polish to open end, reverse or replace the die.
2. Barreled die (center of the die wider than ends) Polish the die to make it cylindrical
3. Edge of punch face turned inside/inward. Polish the punch edges
4. Concavity too deep to compress properly. Reduce concavity of punch faces. Use flat punches.
THE CAUSES AND REMEDIES OF CRACKING RELATED TO FORMULATION (GRANULATION)
Sr. No. CAUSES REMEDIES
1. Large size of granules. Reduce granule size. Add fines.
2. Too dry granules. Moisten the granules properly and add proper amount of binder
3. Tablets expand. Improve granulation. Add dry binders.
4. Granulation too cold. Compress at room temperature
THE CAUSES AND REMEDIES OF CRACKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
Sr. No. CAUSES REMEDIES
1.
Tablet expands on ejection due to air entrapment. Use tapered die.
.
removing tablets
2. Deep concavities cause cracking while
Use special take‐off
THE CAUSES AND REMEDIES OF STICKING RELATED TO FORMULATION (GRANULATION)
CAUSES REMEDIES
Sr. No.
Dry the granules properly. Make moisture analysis to determine
1. Granules not dried properly.
limits.
2. Too little or improper lubrication Increase or change lubricant.
3. Too much binder Reduce the amount of binder or use a different type of binder.
4. Hygroscopic granular material. Modify granulation and compress under controlled humidity.
5. Oily or way materials Modify mixing process. Add an absorbent.
6. Too soft or weak granules. Optimize the amount of binder and granulation technique.
THE CAUSES AND REMEDIES OF STICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
Sr. No. CAUSES REMEDIES
1. Concavity too deep for granulation. Reduce concavity to optimum.
2. Too little pressure. Increase pressure.
3. Compressing too fast. Reduce speed
THE CAUSES AND REMEDIES OF PICKING RELATED TO FORMULATION (GRANULATION)
Sr. No. CAUSES REMEDIES
1. Excessive moisture in granules. Dry properly the granules, determine optimum limit.
Increase lubrication; use colloidal silica as a ‘polishing agent’, so
2. Too little or improper lubrication.
that material does not cling to punch faces.
Low melting point substances, may soften from the heat of Add high melting‐point materials. Use high meting point
3.
compression and lead to picking. lubricants.
4. Low melting point medicament in high concentration. Refrigerate granules and the entire tablet press.
Compress at room temperature. Cool sufficiently before
5. Too warm granules when compressing.
compression.
Reduce the amount of binder, change the type or use dry
6. Too much amount of binder.
binders.
THE CAUSES AND REMEDIES OF PICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
Sr. No. CAUSES REMEDIES
1. Rough or scratched punch faces. Polish faces to high luster.
Design lettering as large as possible.
Embossing or engraving letters on punch faces such as B, A, O, R, P,
2. Plate the punch faces with chromium to produce a smooth
Q, G.
and non‐adherent face.
3. Bevels or dividing lines too deep. Reduce depths and sharpness.
4. Pressure applied is not enough; too soft tablets. Increase pressure to optimum.
THE CAUSES AND REMEDIES OF BINDING RELATED TO FORMULATION (GRANULATION)
CAUSES REMEDIES
Sr. No.
1. Too moist granules and extrudes around lower punch. Dry the granules properly.
2. Insufficient or improper lubricant. Increase the amount of lubricant or use a more effective lubricant
Reduce granular size, add more fines, and increase the quantity of
3. Too coarse granules.
lubricant.
4. Too hard granules for the lubricant to be effective. Modify granulation. Reduce granular size.
5. Granular material very abrasive and cutting into dies. If coarse granules, reduce its size. Use wear‐resistant dies.
6. Granular material too warm, sticks to the die. Reduce temperature.
THE CAUSES AND REMEDIES OF BINDING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS)
CAUSES REMEDIES
Sr. No.
1. Poorly finished dies. Polish the dies properly.
2. Rough dies due to abrasion, corrosion. Investigate other steels or other materials or modify granulation.
Rework to proper size.
3. Undersized dies. Too little clearance.
Increase clearance.
Reduce pressure. OR
4. Too much pressure in the tablet press.
Modify granulation.
THE CAUSES AND REMEDIES OF MOTTLING
CAUSES REMEDIES
Sr. No.
1. A coloured drug used along with colourless or white‐ Use appropriate colourants.
coloured excipients.
2. A dye migrates to the surface of granulation while drying. Change the solvent system,
Change the binder,
Reduce drying temperature and
Use a smaller particle size.
3. Improperly mixed dye, especially during ‘Direct Mix properly and reduce size if it is of a larger size to prevent
Compression’. segregation.
4. Improper mixing of a coloured binder solution. Incorporate dry colour additive during powder blending step, then add
fine powdered adhesives such as acacia and tragacanth and mix well
and finally add granulating liquid.
PROBLEMS AND REMEDIES FOR TABLET COATING
THE CAUSE AND REMEDY OF BLISTERING
CAUSES REMEDIES
Sr. No.
Effect of temperature on the strength, elasticity and
1. Use mild drying condition.
adhesion of the film
THE CAUSE AND REMEDY OF CHIPPING
High degree of attrition associated with the coating Increase hardness of the film by increasing the molecular
1. process. weight grade of polymer.
THE CAUSES AND REMEDIES OF CRATERING
1. Inefficient drying. Use efficient and optimum drying conditions.
Increase viscosity of coating solution to decrease spray
2. Higher rate of application of coating solution.
application rate.
THE CAUSES AND REMEDIES OF PICKING
Use optimum and efficient drying conditions or increase the
Inefficient drying.
1. inlet air temperature.
Decrease the rater of application of coating solution by
2. Higher rate of application of coating solution
increasing viscosity of coating solution.
THE CAUSE AND REMEDY OF PITTING
Dispensing with preheating procedures at the initiation of
coating and modifying the drying (inlet air) temperature such
1.
Inappropriate drying (inlet air ) temperature that the temperature of the tablet core is not greater than the
melting point of the batch of additives used.
THE CAUSE AND REMEDY OF BLOOMING
High concentration and low molecular weight of Decrease plasticizer concentration and increase molecular
1.
plasticizer. weight of plasticizer
THE CAUSES AND REMEDIES OF BLUSHING
1. High coating temperature Decrease the drying air temperatur
Use of sorbitol in formulation which causes largest fall in
Avoid use of sorbitol with Hydroxy Propyl Cellulose, Hydroxy
the thermal gelation temperature of the Hydroxy Propyl
2. Propyl Methyl Cellulose, Methyl Cellulose and Cellulose
Cellulose, Hydroxy Propyl Methyl Cellulose, Methyl
ethers.
Cellulose and Cellulose ethers.
THE CAUSE AND REMEDY OF COLOUR VARIATION
Improper mixing, uneven spray pattern, insufficient
Go for geometric mixing, reformulation with different
1. coating, migration of soluble dyes‐plasticizers and other
plasticizers and additives or use mild drying conditions.
additives during drying.
THE CAUSE AND REMEDY OF INFILLING
Bubble or foam formation because of air spraying of a
1. Add alcohol or use spray nozzle capable of finer atomization.
polymer solution
THE CAUSES AND REMEDIES OF ORANGE PEEL/ROUGHNESS
1. Rapid Drying Use mild drying conditions
2. High solution viscosity Use additional solvents to decrease viscosity of solution.
THE CAUSE AND REMEDY OF CRACKING/SPLITTING
Use lower molecular weight polymers or polymeric blends.
1. Use of higher molecular weight polymers or polymeric blends.
Also adjust plasticizer type and concentration.
Thank ‘u’