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TABLETS

Solid dosage forms containing medicinal substance with diluents/excipients



Advantages of tablets over other dosage forms
Precision of dosage form
Durability of physical characteristics for extended period of storage
Stability of chemical and physiologic activity of drugs
Convenience of administration

Quality Attributes of Tablets
Tablet should include the correct dose of the drug
The appearance of the tablet should be elegant and its weight, size and appearance should be consistent
Drug should be released from the tablet in a controlled and reproducible way
Tablet should be biocompatible, i.e. not include excipients, contaminants, and microorganisms that could cause
harm to patients
Tablet should be of sufficient mechanical strength to withstand fracture and erosion during filling
Tablet should be chemically, physically, and microbiologically stable during the lifetime of the product
Tablet should be formulated into a product acceptable by the patient
Tablet should be packed in a safe manner

Classification of Tablets According to Method of Manufacture
Compressed tablets
o Usually prepared by large scale production methods
Molded tablets (Tablet triturates/hypodermic)
o Involve small scale operations

Compressed Tablets
Sugar coated tablets
Film coated tablets
Enteric coated tablets
Multiple compressed tablets
o Layered tablets
o Press coated tablets
Prolonged action tablets
Tablets for solution
Effervescent tablets
Tableted suppositories or inserts
Buccal and sublingual tablets

Molded Tablets/Tablet Triturates
Dispensing tablets
Hypodermic tablets

Compressed Tablet
Ability to withstand the rigors of the mechanical treatment involved in production, packaging, shipment, and
dispensing
Freedom from defects
Reasonable chemical and physical stability during average storage condition
Ability to release the medicament in reproducible and predictable manner

Components that must be added to the Therapeutic Ingredient are classified according to their purpose and are
grouped into:
Essential components
o Diluent or bulking agent, binders or granulators, distintegrants
Compression aids
o Glidants, lubricants, antiadhesives
Supplementary components
o Colors, flavors, sweetening agents, adsorbents

Diluents
Substances that make up the major portion of the tablet
Lactose, starches, mannitol, sorbitol, sucrose, microcrystalline cellulose

3 factors for choosing diluent
Cost
Biocompatible with other ingredients
Moisture content

Binders
Substances that glue powders together and cause them to form granules
Impart cohesive qualities to the powdered material
Liquid binder if API is not affected by water
Dry if API affected by water
Overwetting too much binder
Underwetting kulang binder
Added in 3 portions
1. Together with API
2. Added to form granules
3. Added before compression
Dependent on the choice of the proper binding agent, quantity used and form of the binder when added
Starch paste (10-20%), aqueous gelatin solution (10-20%), aqueous glucose solution (25-50%), alcoholic solution
of ethylcellulose (5%)

Disintegrant
Material that help the tablet break up and dissolve to release the medicament for rapid dissolution
Starches (corn and potato), clays, cellulose, aligins, gums, effervescent mixtures

Glidants
Materials added to the formulation to enable the granules to flow from a hopper of the tablet press to the die
and for consistent and uniform fill
Talcum, corn-starch
Lubricants
Materials which aid in releasing the compressed tablet from the die
Metallic stearic acid, high melting point waxes, corn starch

Antiadhesives
Materials needed to preven tth eformation of residue fills of tablet granulation on the punches
Talcum, metallic, corn starch



Colorants
FD&C, D&C, free dyes and lakes
Lakes are best adsorbed in aluminum hydroxide. They are almost completely insoluble in water, in which they
may bleed slightly
Photosensitive in varying degrees
Main problem encountered mottling

Flavors and Sweeteners
Frequently used in chewable tablets
Flavors are available as oils and as spray dried beadlets. They are never incorporated during wet processing,
since subsequent drying would reduce the concentration of these volatile ingredients
Aqueous flavors are not recommended since water would interfere with tableting by causing sticking
Lactose, sucrose, mannitol, dextrose, saccharin (500x as sweet as sucrose but with bitter aftertaste)

Adsorbent
Substance capable of holding quantities of fluids in an apparently dry state
Useful when ethereal oils, ethereal solutions of oil-soluble drugs, fluid extracts, and eutectic melts are part of
the tablet formulation
Silicon dioxide possesses a vast surface area, it can hold up to 50% of its weight in water and still as free flowing
powder
Magnesium carbonate, magnesium hydroxide, bentonite, kaolin, magnesium aluminum silicate, tricalcium
phosphate, and dried starch

Tablet Presses
Tablets are formed by the compression of various materials on stamping machines called presses
Basic components of a tablet press consist of hopper, feed frame, dies, punches, and cams
All other parts of a tablet press are designed to control the functioning of those listed above. Features such as
capacity, speed, maximum weight, and pressure vary with the design of the equipment, but the basic elements
remain essentially the same
Basic mechanical unit table compression involves the operation of two steel punches (upper and lower) within a
steel die cavity. These toolings form the tablet.
The tablet assumes the size and shape of the punches and dies used
Curvature of the faces of the punches determines the curvature of the tablets
Weight of the tablet is determined by the volume of the material which fills the die cavity
Thickness can vary due to the density of the granules, pressure applied to the tablet or the speed of tablet
compression

5 basic elements of a tablet press
Hopper san nilalagay the granules
Feed shoe/feed frame transport granules form hopper to die
Upper punch descend to compress
Lower punch ascend to eject
Die decide tablet size and shape

2 Types of Tablet Compression
Single punch - <1000tabs/min
Multistation rotary presses- <100,000tabs/min




Care of Compression Machines


Proper maintenance of punches and dies cannot be overemphasized for a number of valid reasons
Do not allow the punches to drop on concrete or similar hard surfaces which will chip the fine edge.
Never allow the upper and lower punch faces to come in contact with each other
After the completion of a compression run, the roolings are removed from the machine, washed throroughly in
warm soapy water, then dried with clean towel or cloth
Storage in hard paper tubes in which punches are shipped form the factory, or hanging them in wooden racks.
Thorough lubrication is recommended.

Tablet Machines should receive the best possible care to insure maximum operating capacity and Observe the
following rules:
Keep the machines clean
Keep parts properly lubricated
Avoid overloading
Insert dies carefully

Tablet Granulation
Granulation
o Pharmaceutical process that attempts to convert powdered materials into aggregates called granules
o Granules should posses
! Fluidity and
! Compressibility

Good tablet granulation should
Contain particles which approach spherical shape
Present a range of particle sizes that resembles a normal distribution curve, with a small percentage of coarse
and fine particles and with the rest in a narrow range between
Have a uniform distribution of all the ingredients in the formulation
Possess compressible components that will confer physical strength and form to the tablet

Tablet Manufacturing Techniques
Dry Method direct compression and granulation by compression
Wet Granulation Method wet granulation and special procedures/relation granulation processes
o widely used by manufacturer

Dry method
Preferred to wet methods by most manufacturers for economic reasons and stability considerations
Dry processes do not require equipment and handling expenses required in wetting and drying procedures
May obviate loss of activity with those drugs that are moisture- and heat-senstive

Disadvantages of Dry Method
Limited to crystalline substances, such as inorganic salts, NaCl, which may compress directly
Compression of a simple substance may produce tablets that do not disintegrate
When other components are needed, these may interfere with the compressibility of the active ingredient and
then minimize the usefulness of the method
Effective dose of many drugs is so small that direct compression would be impractical and unenconomical
To mitigate these problems, the active ingredients is mixed with a directly compressible vehicle such as sptray
dried lactose, anhydrous lactose, calcium phosphate, mannitol, sorbitol, microcrystalline cellulose



Granulation by Compression
Also known as dry granulation, precompression or double compression method
Involves compaction of finely divided powdered materials into large, poorly formed but firm masses called slugs.
These are subsequently screened or milled in order to produce a granular form of tableting material possessing
the essential characteristics of a good granulation

Dry granulation method includes the following steps
Weighing of ingredients
Mixing of ingredients in a suitable mixer of blender
Slugging by using flat face punches 7/8 to 1 inch diameter
Dry screening of slugs through a mesh screen (by hand) or through a Fitzpatrick comminuting mill
Lubrication through a suitable blender
Compression into final tablets
Bolting - addition of lubricant prior to compression

Wet Granulation
Most widely used and most general method for preparing a tablet granulation that will satisfy the physical
requirements for the compression of good tablets

Disadvantages of Wet method
Involves several separate steps
Requires longer processing time
Labor cost is high

Steps in the Wet Method
Weighing of the ingredients
Mixing them in a suitable mixer of blender
Granulating them into a damp mass by the addition of a binding solution
Screening the mass by forcing through a 6- or 8- mesh screen
Drying in suitable ovens of fluid bed dryers
Dry screening through smaller mesh screen (see next table)
Lubrication in a suitable blender (Bolting)
Compression into final tablets
Recommended Screen size for Dry Screening Granulation
Tablet size (diameter)
Screen size
Up to 3/16 inch

20 mesh

7/32 to 5/16 inch

16 mesh

11/32 to 13/32 inch

14 mesh

7/16 inch and larger

12 mesh


Special Procedures to Promote Fluidity and Compressibility of Materials by Forming beads:
Spheronization
Spray drying
Spray congealing or spray chilling

Spheronization
Form of pelletization which consists of extruding a wet granulation containing the API, diluent and binder into
the spheronization equipment called Meramurizer machine

Extruded rob shaped cylindrical segments are shaped into spheres by centrifugal and frictional forces on a
rotating screen.
The pellets are then dried by conventional methods, mixed with suitable lubricants and compressed into tablets


Advantage of spheronization
Production of granules which are regular in shape size and surface characteristics
Low friability resulting in fewer fines
Ability to regulate the size of the spheres

Spray drying
Consists of bringing together a highly dispersed liquid and a sufficient volume of hot air to produce evaporation
and drying of the liquid droplets
The feed liquid may be a solution, slurry, emulsion, gel or paste, provided it is pumpable and capable of being
atomized

Spray-Congealing or Spray-Chilling
Similar to spray drying and uses the same basic equipment
Main difference lies in the absence of heat in the process
Consists of melting solids and reducing them to beads of powder by spraying the molten feed into a steam of
ambient or cooled air or other gas. The choice of the latter depends on the freezing point of the product

Processing Problems
Cappping
o Partial or complete separation of the top or bottom of the tablet from the main body
Chipping
o Separation of small piece of tablet after ejection
Lamination
o Separation of a tablet into 2 or more distinct layers
Picking
o Removal or material from the surface of the tablet, and its adherence to the face of the punch
Sticking
o Adhesion of granulation to the die wall
Mottling
o Unequal distribution of color on the surface of the tablet, with light or dark areas standing out in an
otherwise uniform surface
Capping, chipping and lamination might be due to uneven distribution or uneven size or granules

Factors that may cause Splitting of Tablets
Excess fines or powder with entraps air in the tablet mixture
Deep markings on tablet punches
Worn and imperfect punches
Worn dies
Too much pressure
Unsuitable formula
Moist and soft granulation
Poorly machined punches
Remedies to prevent picking or sticking
Desing letterings as large as possible particularly on punches with small diameters
Reformulate to produce a larger tablet
Plate the punch surface with chromium to produce smooth nonadherent face
Add a polishing agent such as colloidal siliva
Add more binder or change the binder to make granules more cohesive

Dilution of low melting API or additive with high melting materials will prevent softening of the granules due to
heat of compression and may increase tablet size
Refrigeration of the press and granulation containing high concentration of low melting medicaments
Redry the granulation
Several factors which may cause mottling
A drug that differs in color from its excipients or whose degradation products are highly colored. The former is
masked by the use of a dye
Migration of dye during a granulation can be remedied by change of the solvent system, reduction of drying
temp, reduction of granulation to smaller particle size
Addition of hot colored adhesive solution to a much cooler powder mixture will produce mottling because the
adhesive that comes out of the solution carries most of the color with it. Remedies to this situation are further
setting, incorporate the adhesive before adding the granulating fluid and disperse the dry color additive during
the powder blending

USP official test for tablets
Weight variation
Hardness variation
Double impression only for tablets
Tablet disintegration
Tablet dissolution
Tablet friability

Tablet coating Application of a coating material to the exterior of a tablet with the intention of conforming benefits
and properties to the dosage form over uncoated variety.

Solid dosage form are coated for several reasons
To mask unpleasant taste
To protect components form atmospheric degradation
To prevent contact with a drug which is irritating or potentially allergenic
To separate reactive ingredients
To control the site of drug release (enteric coating)
To delay or prolong absorption of the drug component by retarding release of drug from the dosage form
(sustained release)
To improve appearance
To change the physical surface characteristics of ing. (surface modification)

Tablet coating have been classified into 4 basic categories:
Sugar coating
Film coating ( non-enteic and enteric)
Compression
Other new concepts

Basic processes used in the application of coating
Pan coating
Air suspension coating
Dip coating
Tablet compression coating

Pan coating parang cement mixer
Process is used in both sugar and film coating
Makes use of coating pans provided with hot and cold air input system and an exhaust system to remove
moisture and find powder generated during the coating operation

Other necessary equipment includes stem jacketed tanks for the preparation of the liquids used, drying ovens
necessary in the process and polishing drums
Most widely used by the industry


Air suspension coating parang fluidized bed dryer
Most dependable methods for applying film coats
Film materials is atomized and applied to tablets as they are suspended inside the columnar coating chamber by
means of a stream of hot air
Major problems associated with the air suspension coater is breakage
As the tablets travel up the center of the column in the main stream, velocities are so high that collusions
between tablets and the wall of the coating chamber may produce excessive tablet breakage. Therefore, it is
essential that tablets to be subjected to the process be formulation for minimum friability and be strong enough
to withstand the harsh coating conditions

Dip coating quezo de bolaahhh :O
Materials to be coated are usually placed in baskets and dipped into containers of coating solutions. The wet
tablets are then agitated or tumbled in coating pans during drying to prevent adherence to each other. The
process can be repeated a number of times after each coat is sufficiently dry
Has not been widely accepted because of difficulties encountered during coating procedure and lack of coat and
uniformity

Compression coating
Makes possible some special dosage forms
Two incompatible drugs may be separated by placing one in the core, the other in the coating
Slow release formation may be placed in a core coated with a fast releasing granulation for immediate effect.
Cores may also be enteric coated for delayed release
2 types of equipment have been created: One compresses a coating around the cored that have been made on
another press, the other compresses the cores on one turret and immediately transfers them to second for the
application of the coating
Sugar coating
Most widely used
Involves several basic steps
1. Sealing done to separate the core from the water that is used in the coating process. Waterproofing
materials such as cellulose acetate phthalate, zein, shellec, and specific resins are adhesivs in nature

- Dusting compounds such as asbestos- free talc and terra alba are applied in between 2 seal
coats up to 6 seal coasts to prevent the tablets from sticking with one another and to the coating pan
2. Subcoating applied to round off the tablet contour rapidly, to improve the bond between the seal coat and
the sugar coat, and to build up or standardize tablet size. Solutions used to subcoat are usually gelatin
and/or acacia
3. Syruping syrup containing and dyeing phase of the process is particularly demanding. It usually involves 3
basic phases such as grossing, heavy sugar coating and regular sugar coating
4. Finishing initiated when the desired color is attained. Three or 4 coated of regular syrup are applied rapidly
without permitting the tablet bed to become dusty
5. Polishing- done in a canvas polishing pan by allowing the coated tablets to roll in wax solution until high
luster is produced
6. Printing not talaga kasama sa steps of coating
- Any print should be distinct, no smudging or broken print

Common coating fault for sugar coated tablets
Process defects spitting of coat on storage caused by inadequate drying during the coating application






Film coating
Recent development which makes use of cellulose polymers, povidone and low to medium MW glycols as film
polymers
One step lang : deposition spray lang a thin film of polymer surrounding the tablet core
The coating liquid/solution contain a polymer in a suitable liquid medium together with the other ing. like the
pigment or plasticizer (not sure, ang hina ng voice ni maam huhu )
The solution is sprayed in a rotating mix tablet bed or fluid bed, drying condition permit the removal of the
solvent so as to leave a thin deposition of coating material around each tablet core.

Film coating suspension formulation
Polymer cellulose derivatives (hydroxypropyl methylcellulose), methacrylate amino ester copolymer
Plasticizer PEG 400, organic esters (diethyl phthalate), oils/glycerides (fractionized coconut oil)
Colorants iron oxide pigments, titanium dioxide, aluminum lakes
Solvents organic solvents
****Drawback is the use of organic solvent kasi expensive, volatile, therefore flammable and leaves residues, and
can cause environmental hazards

Brand of Machine for film coating
Accela Cota UK
Hi coater Japan
Driacoater Germany
HTF-150 - Italy
IDA- France

Basic process requirement for film coating
Adequate means of atomizing the spray liquid for application to the tablet core
Adequate mixing and agitation of the tablet bed
Sufficient heat input in the form of drying air to provide the latent heat of evaporation of the solvent
Good exhaust facilities to remove dust and solvent laden air

Ideal characteristics of film coated tablets
Should display an even coverage of film and color
there should be no abrasion of tablet edges of crowns
Logos and break lines should be distinct and not filled in
Tablet must also be compliant with finished product specifications and any relevant compendial requirements

Coating faults (film)
Processing - inadequate drying conditions will permit coating previously deposited on the tablet surface to stick
against neighboring tablets. When parted, this will reveal original core surface underneath
Formulation faults film cracking or bridging of breaking lines

Advantages of film coating in place of sugar coating
Reduction in coating time and material cost
No significant increase in tablet weight
No undercoate or waterproof coat required
Durability and resistance of chipping and cracking
Allows monogramming identification of product

Provides effective protection to light, air and moisture


No adverse effect on disintegration time
Pharmaceutically elegant
Provide the opportunity to use non-aqueous coating solutions
Standardization of process and materials
Major differences between sugar and film coated tablets
Features
Sugar Coating

Film coating

Time

At least 8 hrs

1.5 2 hours

Appearance

Rounded with high degree of polish

Retains contour of original core


Usually not as shiny as sugar coat
types

Weight increase due to coating 30-50%


materials

2-3%

Logo or break lines

Not possible

Possible

Other solid dosage forms

Coating possible but little industrial Coating of multiparticulates very


importance
important in modified release forms



Other types of coating
Compression coating
Electrostatic coating
Laminated coating

Compression coating
Makes use of sophisticated tablet compression machine which compresses a coating or shell around a core that
has been compressed on another press

Electrostatic coating
Employed to apply films to conductive materials by imparting an ionic charge to the substrate and an opposite
charge to the coating materials. This ensures a thin and continuous film to the surface
Laminated coating
Provides a second action or layer of medicament for tablet as in
1. A repeat action tablet, in which a portion of the drug is in the outer lamina or coating
2. Enteric tablets, in which one drug may be made available for gastric absorption and another ( or more of the
same) is released in the intestine
3. Buccal swallow tablet, which is admistered first SL, and upon signal, such as release of a flavor from the
inner core, tablet is swallowed and proceeds to disintegrate as a normal per oral(?) tablet.

Mangifera indica haha;)