DDS LEC - Solid Dosage Forms: Tablets Part I

Tablets

• Solid dosage form which may or may not contain medicinal substances with or without diluents prepared either by compression or molding

• Can be made in various shape, weight, hardness, thickness, disintegration, and dissolution characteristics

• Can be scored/grooved for altering dose and easier administration

  • Not applicable for sugar-coated

Advantages of Tablets

• Precision of Dosage

• Convenience of Administration

• Physicochemical Stability

• Durability

Active Pharmaceutical Ingredient (API)

• Components intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure or function of the body

• Example:

  • Paracetamol

Diluents/Fillers/Bulking Agents

• Inert filler to create desired bulk, flow properties, and compression characteristics of tablets and capsules

• Examples:

  • Lactose

  • Starch

  • MCC

  • Mannitol

  • Dextrose

Binders or Adhesives

• Substances used to cause adhesion (glues powders to form granules) of powder particles in tablet granulations

• Examples:

  • Acacia

  • Tragacanth

  • PVP

  • Starch Paste

  • Sodium Alginate

Disintegrants

• Promotes disruption of the mass into smaller particles more readily dispersed or dissolved

  • Intragranular Disintegrant

  • Extragranular Disintegrant

  • Superdisintegrant

Intragranular Disintegrant

• Promotes disruption from small particles (granules) into powders

• Added prior to granulation

Extragranular Disintegrant

• Promotes disruption from tablets to small particles

• Added prior to compression

Superdisintegrants

• Has both intragranular and extragranular properties

• Added prior to compression

  • Croscarmellose - swells up to 10x

Croscarmellose

A cross-linked cellulose that swells up to 10x when in contact with water, crospovidone, Sodium starch glycolate

Flow Activators

• Enhances the flow of granules during compression

  • Lubricant

  • Glidant

  • Anti-adherents

Lubricant

Agents that act between surfaces in relative motion to prevent punches and dies.

• Stearic acid

• Polyethylene Glycol (PEG)

• Sodium Lauryl Sulfate (SLS)

Glidant

Agents that improves the flow characteristics of granules through the tablet press.

• Talc (5%)

• Corn Starch

• Magnesium stearate (≤1%)

• Cab-O-Sil

Anti-adherents

Prevents tablet ingredients from sticking to punches and dies during production (stickin) - a tablet defect.

• Magnesium stearate

• Talc

• Starch

• Cellulose

Miscellaneous Adjuncts

Provide color and flavor

• FDC Red 40 (allura red)

• FDC Yellow 6 (sunset yellow)

• FDC Yellow 5 (tartrazine)

• FDC Blue 2 (indigotine)

Compressed Tablets

• Manufactured with tablet machines capable of exerting great pressure in compacting the powdered or granulated material

• After compression, _____ _____ can be coated with various materials

  • Sugar-coated

  • Enteric-coated

  • Film-coated

Multiple Compressed Tablets

• Prepared by subjecting the fill material to more than 1 compression

• Starts by initial compaction of fill material in a die followed up by additional fill material and compression

• Results to a multiple-layer tablet or a tablet within a tablet

• Done to combine 2 APIs in 1 dosage form

• Done to increase its pharmaceutical elegance

Synergistic Activity

An interaction between 2 or more drugs that causes the total effect of the drugs to be greater than the sum of the individual effects of each drug

Film-Coated Tablets

• Compressed tablets coated with a thin layer of a polymer capable of forming a skin-like film

• Same function with sugar-coated tablets but less bulky, less time-consuming, and more durable

• Designed to rupture and expose the core tablet at the desired location in the GI tract

Gelatin-Coated Tablets

• Capsule-shaped compressed tablet

  • Gelatin - Primary component of capsule shells

• More tamper resistant than unsealed capsules

• Innovator Product: Gelcap

Enteric-Coated Tablets

• Compressed tablets coated with substances that resist acid degradation in the stomach but disintegrated in the intestine to allow drug absorption

• Example:

  • Bisacodyl (Dulcolax) - Pro-drug, converted to bis-hydroxyphenylpyridylmethane (BHPM) upon reacting with intestinal deacetylase enzyme

Methods of Tablet Manufacture

• Dry Granulation

• Wet Granulation

• Fluid Bed Granulation

Dry Granulation

• Making granules by applying pressure

• Powder → Granules → Tablets

• Involves compaction of the components of a tablet formulation into slugs, followed by milling and screening prior to final compression

• Used for moisture and heat-sensitive drugs

Granules

Dry aggregates of powdered particles

Slugs

Granules produced in dry granulation

Dry Granulation Process

1. Grinding/Milling - reduces particle size to desired size or size range

2. Mixing - utilizes V-shape blender for homogenous mixing

3. Slugging - creation of slugs using roller compactor; crushed to create granules

4. Screening - ensure particle size uniformity

5. Mixing - addition of lubricants or flow activators

6. Compaction/Compression - passes through the tablet press machine to create the tablet

Wet Granulation

• Process of converting the drug and excipient into granules that flows well into dies

• Involves wet massing and wet screening of the powders

Wet Granulation Process

1. Grinding/Milling - reduces particle size to desired size or size range

2. Mixing - utilizes V-shape blender for homogenous mixing

3. Wet Massing - add binder solutions to create wet mass or agglomerate (big lump); undergo screening; mesh #4

4. Drying - moisture content must be within 2-3%

5. Screening - ensure particle size uniformity

6. Mixing - addition of lubricants or flow activators

7. Compaction/Compression - passes through the tablet press machine to create the tablet

Fluid Bed Granulation

• The entire process of wet granulation is done in a continuous process

• Using fluid bed granulator

Fluid Bed Granulation Process

1. Pre-Blending

2. Wet Granulation - spraying of liquid binder solution

3. Drying - drying to desired moisture content (2-3%)

Tablet Compression Stages

1. Filling - powdered granules are loaded into the die cavity of the tablet press

2. Metering - ensures equal amounts of granules will be loaded into the cavity

3. Compression - granules are compressed or pressed to form a solid tablet

4. Ejection - the formed tablet is released from the cavity aided by the ejection cam

Tablet Compression Stage Filling

Powdered granules are loaded into the die cavity of the tablet press

Tablet Compression Stage Metering

Ensures equal amounts of granules will be loaded into the cavity

Tablet Compression Stage Compression

Granules are compressed or pressed to form a solid tablet

Tablet Compression Stage Ejection

The formed tablet is released from the cavity aided by the ejection cam

Basic Parts of a Tablet Press Machine

• Hopper

• Feed Shoe

• Die Cavity

• Upper Punch & Lower Punch

Hopper

Stores the granules for compression

Feed Shoe

• Distributes the granules in the die cavity

• Feeds the granules from the hopper to the die cavity

Die Cavity

• The mold of the tablet machine

• It controls the size and shape of the tablet

Upper Punch & Lower Punch

Compresses the granules

Compression-Related Tablet Defects

• Capping

• Cracking

• Mottling

• Soft Tablet

Capping

• Separation of a portion of upper or lower tablet

• Due to:

  • Air Entrapment - presence of air in granules before compression

  • Excessive Fine Granules - excessive fines, doesn’t follow the golden ratio

Cracking

• Presence of fine cracks around the surface of the tablet

• Due to:

  • Overcompression - pressured exerted by upper & lower punch is too excessive

  • Poor Granulation - can have excessive fine granules just like capping

Mottling

• Improper coloration/blemishes on the surface of the tablet

• Due to:

  • Poor Tablet Design - improper coloration shows that there’s incompatibilities or reaction in drug/excipients

Soft Tablet

• Brittle Tablet

• Easily breaks down

• Due to:

  • Undercompression - tablet easily breaks upon handling

Tablet Coating Mechanisms

• Sugar Coating

• Film Coating

• Fluid Bed Coating

Sugar Coating

Coating that increases tablet weight by 30-50%

Steps in Sugar Coating

1. Sealing/Waterproofing - applied to tablet core to protect against water penetration; includes Shellac, Cellulose Acetate Phthalate (CAP), and Hydroxypropylmethylcellulose (HPMC)

2. Sub-coating - rounds the tablet edges which increases tablet weight; include Scrose & Binder Solution and Gum Solution

3. Grossing/Smoothing - making the sub-coat surface smooth and even using Syrup Solution (60-70%)

4. Coloring - gives tablet its color and finished size; uses dyes and lakes

5. Polishing - produces characteristic gloss; uses besswax and carnauba wax

Sealing/Waterproofing

• Applied to tablet core to protect against water penetration

• Includes:

  • Shellac

  • CAP - Cellulose Acetate Phthalate

  • HPMC - Hydroxypropylmethylcellulose

Sub-coating

• Rounds the tablet edges which increases tablet weight

• Include:

  • Sucrose & Binder Solution - used if it will be done under a lamination process

  • Gum Solution - used if it will be ddone under a suspension process

Sucrose & Binder Solution

Used if sub-coating will be done under a lamination process

Gum Solution

Used if sub-coating will be done under a suspension process

Grossing/Smoothing

Making the sub-coat surface smooth and even using Syrup Solution (60-70%)

Coloring

• Give color and finished size to tablet

• Uses:

  • Dyes

  • Lakes

Polishing

• Produces characteristic Gloss

• Uses:

  • Besswax

  • Carnauba Wax

Film Coating

Coating that may be non-aqueous or aqueous

Nonaqueous Solutions Component

• Film Former - produces a smooth thin film

• Alloying Substance - provides water solubility or permeability to the film

• Plasticizer - produces flexibility and elasticity of coat

• Surfactant - enhances spreadability

• Opaquant and Colorants

• Sweeteners and Flavorants

• Glossant - provides a luster to the tablets

• Volatile Solvent - allows spread of other components over the tablets

Film Former

Produces a smooth thin film

• Cellulose Acetate Phthalate (CAP)

Alloying Substance

Provides water solubility or permeability to the film

• Polyethylene Glycol (PEG)

Plasticizer

Produces flexibility & elasticity of coat

• Castor Oil

Aqueous Solutions Component

• Film-forming polymer (7% to 18%)

• Plasticizer (0.5% to 2.0%)

• Colorant (2.5% to 8%)

• Vehicle (qs. ad. to 100%)

Fluid Bed Coating

• Spray coating of powders, granules beads, pellets, or tablets held in suspension by a column of air

• Utilizes the continuous stream of air to evenly administer/apply the coating or granulation solution in the granules

Top-Spray Fluidized-Bed Coating

Coating solution is applied at the top of the floating tablets

Botton-Spray Fluidized-Bed Coating

Coating solution is applied at the bottom of the floating tablets

Tangential-Spray Fluidized-Bed Coating

Coating solution is applied at the middle of the floating tablets

Coating-Related Tablet Defects

• Blistering

• Chipping

• Cratering

• Picking

• Blooming

• Blushing

• Infilling

• Mottling

Blistering

• The film becomes locally detached from the substrate forming a blister

• Due to:

  • Air Entrapment Due to Overheating - too high temperature used during the coating process upon drying to make the coat stick to the coat tablet

Chipping

• Chipped and dented at the edges of the tablet

• Due to:

  • Rough Coating Pan - edges of the coating pan are too rough, resulting in possible dents or chips around the tablet

Cratering

• Volcano-like crater appearance

• Due to:

  • Inefficient Drying - moisture or solvent in the coating layer fails to evaporate

  • Excessive Rate of Coating - applying the coating solution too quickly or in excessive amounts

Picking

• Some areas of the film pull away from the surface

• Due to:

  • Uneven Sticking - film did not stick evenly to the surface of the core tablet

Blooming

• Dulling (pamumutla) of the coating

• Due to:

  • Excessive Plasticizer - can lead to migration of the plasticizer to the surface over time, creating a dull or “bloomed” look

Blushing

• Whitish specks or haziness in the film

• Due to:

  • Precipitation of Polymers - precipitate out if the coating environment is not controlled properly which causes the polymers to separate from the solution, forming whitish or cloudy areas in the film coating

Infilling

• Same effect as bridging, logo, or the monogram is filled with solidified foam structure

• Due to:

  • Foam Formation - there are solidified foams that enter on the imprints making it less viable

Molded Tablets

• Can be called Tablet Triturates

• Usually made from moist material

• Usually soft and are rapidly soluble in water

• Triturate mold is used to give a cylindrical shape

  • Upon molding, add alcohol into molds to have a unified size and for it to stick into a molded tablet

• Diluent: Lactose and Sucrose

Hypodermic Tablets

• Soft, readily-soluble tablets used for preparation of solutions to be injected

  • Dissolved in sterile water and then injected

• Disadvantage: Difficulty in ensuring sterility of the preparation

  • Since there is a creation of a sterile solution, it needs to have a sterile area for it to be made

• No _____ _____ have been recognized in compendia

Dispensing Tablets

• Contains large amounts of highly-potent drugs substances to obtain pre-measured amounts for compounding multiple dosage units

• No longer in use as this had the dangerous potential of being inadvertently dispensed to patients

  • It needs to be diluted into pre-measured amounts, resulting in errors in compounding and possible toxic effects due to overdose

Lozenges

Made using a high degree of compression to produce harder than ordinary tablets so that they dissolve and integrate slowly in the mouth

• Strepsils

Vaginal Tablets

• Uncoated bullet-shaped or ovoid tablets inserted into the vagina for local effects

• Packaged with a plastic inserter for convenient placement of the tablet in the vagina

  • Clotrimoxazole (Canesten)

Lollipops

Sugar-based lozenge on a stick

• Fentanyl Citrate

Pills

• Small, round dosage forms intended for oral administration

• Prepared by wet massing before molding

  • Contraceptives