prelim 3.1 - manufacture of tablets

__________ should be prevented for all products by appropriate design and operation of manufacturing facilities

Cross-contamination

__________ should be installed in such a way as to prevent any risk of error or of contamination

Equipment

In __________, before any processing operation is started, steps should be taken to ensure that the work area and equipment are clean and free from any starting materials

Line clearance

Record that contains manufacturing formulae, processing, packaging, and testing instructions

Manufacturing batch record (MBR)

Record that should be kept for each batch or part batch processed

Batch packaging record

Are solid dosage forms prepared by compression or molding that contains medicinal substances with or without suitable excipients and/or other pharmaceutical adjuncts

Tablets

Compressed, molded, hypodermic, dispensing, coated (Types of tablets according to)

Process of manufacture

Immediate-release, chewable, buccal, sublingual, vaginal, ER (Types of tablets according to)

Delivery system

Effervescent, instantly disintegrating (Types of tablets according to)

Content functions

Are manufactured with tablet machines capable of exerting great pressure in compacting the powdered or granulated material (Types of tablets)

Compressed tablets

Compressed tablets with multiple layers (Types of tablets)

Multiple compressed tablets

Tablets that are coated depending on the materials (Types of tablets)

Coated tablets

Tablets with sugar layer (Types of coated tablets)

Sugar coated

Tablets with thin layer of polymer (Types of coated tablets)

Film coated

Diluents, granulating agents, flow activator, and disintegrant are __________ excipients

Essential

Colorant, flavor and sweetener, adsorbent, and surfactants are __________ excipients

Less essential

An inert substance added to increase tablet size to a manageable size (Excipients)

Diluent (Bulking agent/filler)

Lactose, starch, dextrose, mannitol, sorbitol (Excipients)

Diluent (Bulking agent/filler)

Substance that “glue” powders together and cause them to form granules (Excipients)

Granulating agent (Binder/adhesive)

Water, alcohol, starch paste, acacia mucilage, gelatin solution (Excipients)

Granulating agent (Binder/adhesive)

Includes lubricant, glidant, and anti-adherent (Excipients)

Flow activator (Antifrictional agent)

Acts between surfaces in relative motion to prevent friction and wear (Excipients)

Lubricant

Magnesium stearate (most effective), stearic acid, SLS, liquid paraffin (Excipients)

Lubricant

Improves the flow characteristics of granulations (Excipients)

Glidant

Talc, cornstarch, Cab-O-Sil, Syloid or Aerosil, magnesium stearate (Excipients)

Glidant

Prevents granulations from sticking to the faces of the punches and die walls (Excipients)

Anti-adherent

Talc, magnesium stearate, starch, cellulose (Excipients)

Anti-adherent

To aid the break-up of the tablet when it reaches a liquid medium (Excipients)

Disintegrant

Explotab, Croscarmellose, Crospovidone, Ac-Di-Sol, starch (Excipients)

Disintegrant

Disintegrants that are mixed with other ingredients prior to granulation and thus be incorporated within the granules (Types of disintegrants)

Intragranular disintegrant

Disintegrant is mixed with the dry granules before the complete powder mix is compacted (Types of disintegrants)

Extragranular disintegrant

Facilitates water uptake; facilitates transport of liquid into the pores of the tablet to form smaller fragments (MOA of disintegrant)

Wicking

Facilitates rupture of the tablet; swelling of the disintegrant particles during sorption of water (MOA of disintegrant)

Swelling

Disguising of off-color drugs, product identification, and production of a more elegant product (Excipients)

Colorant

Dyes applied in solutions (Colorants)

FD&C and D&C dyes

Dyes that have been absorbed on a hydrous oxide and employed as dry powders for coloring (Colorants)

Lakes

To give the tablet a more pleasant taste or to mask an unpleasant one (Excipients)

Flavorant

Flavor oils (Excipients)

Flavorant

Limited to chewable tablets to exclude or limit the use of sugar in the tablets (Excipients)

Sweetener

Because tablets are made by “compression”, the stamping machines are called __________

Presses

For holding and feeding granulation to be compressed (Basic components of tablet compression machine)

Hopper

Define the size and shape of the tablet (Basic components of tablet compression machine)

Dies

For compressing the granulation within the dies (Basic components of tablet compression machine)

Punches

For guiding the movement of the punches (Basic components of tablet compression machine)

Cam tracks

Forces granules into die cavity (Auxiliary equipment)

Granulation feeding device

Monitors force at each compression station (Auxiliary equipment)

Tablet weight monitoring devices

Removes excess powder (Auxiliary equipment)

Tablet deduster

Chills the compression components to allow the compression of low melting point substance such as waxes (Auxiliary equipment)

Fette machine

Output is 200 tablets/min; small-scale production (Tablet press classifications)

Single press (Eccentric press)

Output is 10,000 tablets/min; large-scale production (Tablet press classifications)

Rotary press (Multistation press)

__________ depends on the methods of granulation

Unit operations

Process of reducing larger size solid unit masses to smaller size unit masses by mechanical means

Size reduction (Milling, sizing, crushing, grinding, pulverization)

3 basic methods of tablet compression (DDW)

Direct compression, Dry granulation, Wet granulation

Fluid energy mill, colloidal mill, ball mill, hammer mill, cutting mill, roller mill, and conical mill are used for __________

Size reduction

Involves pregranulation and/or post granulation stage of tablet manufacturing

Mixing

Oblicone blender, container blender, tumbling blending, agitated powder blender, and bin blender are used for __________

Mixing

Used for soluble drugs and potent drugs (Methods of tablet compression)

Direct compression

Spray dried lactose, Sta-Rx 1500, Emdex, Celutab, and Avicel are examples of _________

Compressible diluents

NaCl, NaBr, KCl are examples of __________

APIs

Used for drugs that do not compress well after wet granulation and for moisture and heat sensitive drugs (Methods of tablet compression)

Dry granulation

Refers to the formation of a large tablet (slug)

Slugging

Process of squeezing the mix between two rollers to produce a sheet of material

Roller compaction

Examples include aspirins (esters) and vitamins (Methods of tablet compression)

Dry granulation

Granules are formed by binding the powders together with an adhesive (Methods of tablet compression)

Wet granulation

Examples include paracetamol and amides (Methods of tablet compression)

Wet granulation

Process of massing of the powder mix using a solvent (alone or with a granulating agent)

Wet massing

2 solvents used in wet massing (WO)

Water, Organic solvents

Nonflammable, non toxic, long drying time (Solvents used in wet massing)

Water

Alternative to dry granulation; for water-sensitive drugs; rapid drying (Solvents used in wet massing)

Organic solvents

Process that breaks agglomerates of granules and removes fine material, which can then be recycled

Screening

__________ are the ones that pass through sieve 20 and are retained on sieve 40

Good granules

__________ are the ones that pass through sieve 40

Fines

Adapted for wet granulation and dry granulation using a fluid bed unit (Methods of tablet compression)

Fluid bed granulation

3 steps in fluid bed granulation (PGD)

Preblending, Granulating, Drying

Compressed tablets surrounded by sugar coating (Types of coated tablets)

Sugarcoated tablets

Provides a moisture barrier and harden the tablet surface (Steps in sugarcoated tablets)

Sealing/waterproofing

Causes a rapid buildup to round off the tablet edges (Steps in sugarcoated tablets)

Subcoating

Smooths out the subcoated surface and increases the tablet size to predetermine dimension (Steps in sugarcoated tablets)

Grossing/smoothing

Gives the tablet its color and finished size (Steps in sugarcoated tablets)

Coloring

Produces the characteristic gloss (Steps in sugarcoated tablets)

Polishing

Uses shellac, zine, and cellulose acetate phthalate (CAP) (Steps in sugarcoated tablets)

Sealing/waterproofing

Uses gum-based solution (Steps in sugarcoated tablets)

Subcoating

Uses syrup solution (Steps in sugarcoated tablets)

Grossing/smoothing

Uses syrup solution containing colorant (Steps in sugarcoated tablets)

Coloring

Uses beeswax, carnauba wax, candelila wax, or hard parrafin wax (Steps in sugarcoated tablets)

Polishing

These are compressed tablets that are covered with a thin layer or film of a water-soluble material (Types of coated tablets)

Film coated tablets

HPMC, Povidone, Na CMC, PEG, Acrylate polymers (Materials of film-coated tablets)

Film formers

Water, ethanol, methanol, isopropanol, chloroform (Materials of film-coated tablets)

Solvents

Castor oil, glycerin, lower molecular weight, PEG (Materials of film-coated tablets)

Plasticizers

Opasray and opadry (Materials of film-coated tablets)

Colorants

Titanium dioxide, silicates, carbonates, oxides, and hydroxides (Materials of film-coated tablets)

Opaquant-extenders

Flavors, sweeteners, surfactants, antioxidants, antimicrobials (Materials of film-coated tablets)

Miscellaneous coating solution components

Appearance - rounded with high degree of polish (Sugar coating or film coating)

Sugar coating

Appearance - not as shiny as sugar coat and retains contour (Sugar coating or film coating)

Film coating

Weight increase - 30-50% (Sugar coating or film coating)

Sugar coating

Weight increase - 2-3% (Sugar coating or film coating)

Film coating

Logo lines - Not possible (Sugar coating or film coating)

Sugar coating

Logo lines - Possible (Sugar coating or film coating)

Film coating

Other solid dosage forms - Coating possible but little importance (Sugar coating or film coating)

Sugar coating

Other solid dosage forms - Very important in modified release forms (Sugar coating or film coating)

Film coating