TOPIC 5: TABLETS

At the end of the topic, the students should be able to:

a. Enumerate the following:

i. Advantages and disadvantages of tablets.

ii. General properties of tablet dosage forms.

2. Classify the different pharmaceutical ingredients used in the manufacture of tablets.

3. Understand various pharmaceutical processes involved for solid dosage form.

a. Describe the following:

i. Methods used for the manufacture of tablets.

ii. Tablet coating

4. Discuss the different tablet defects encountered in the manufacture of tablets.

5. Discuss the pharmaceutical tests conducted to ensure good quality of tablets.

A. WHAT ARE TABLETS?

Solid pharm dfs containing drug substances

Can be compressed or molded

Advantages of tablets

1. Production Aspect

a. Large scale production at lowest cost

b. Easiest and cheapest to package ship

c. High stability (compared to liquids but not as high as capsule)

2. User aspect (doctor, pharmacist, patient)

a. Easy to handle; lightest and most compact

b. Greatest dose precision and least content variability

c. Mask unpleasant tastes

d. Improve px compliance

Disadvantages of tablets

1. Px w difficulty in swallowing tabs or unconscious px

2. Some drugs resist compression into dense compacts

3. Drugs w poor wetting, slow dissolution, intermediate to large dosages

4. Bitter taste drugs, drugs w an objectionable odor, or sensitive to oxygen moisture

Ideal properties of tablets

2. Have the strength to withstand the rigors of mechanical shocks encountered in its production, packaging,
shipping and dispensing

3. Release the medicinal agents in the body in a predictable and reproducible manner

4. Elegant product, acceptable size and shape

5. Chemical and physical stabilities

B. TYPES OF TABLETS

1. Based of routes of administration

a. Oral

Tablets ingested orally:

i. Compressed tablet

ii. Multiple compressed tablet

iii. Modified-release tablet

iv. Sugar coated tablet

v. Film coated tablet

vi. Effervescent tablet

vii. Chewable tablet

Tablets used in oral cavity

i. Buccal tablet

ii. Sublingual tablet

iii. Troches or lozenges

iv. Dental cone

Tablets administered by other route:

i. Implantation tablet

ii. Vaginal tablet

2. Production Process

a.

Compressed tablets

i. Multipe compressed tablets (Neozep – active ingredients are incompatible)

Prepared by subjecting the fill material to a more than a single compression

Multiple layer tablet

Inner tablet (core), outer portion (shell) – tablet within a tablet

ii. Sugarcoated tablets

Protect from environment such as O2, improve taste and mask odor, enhance appearance, identification

May add up to 50% to the wt and bulk of the uncoated tab

iii. Film-coated tablets

Compressed tab coated w a thin layer of polymer capable of forming skinlike film

More durable, less bulky, and less time consuming in coating compared to sugarcoated tabs

iv. Gelatin-coated tablets

Innovator product: gelcap (1/3)

Capsule-shaped compressed tab

Allows the coated product to be about 1/3 smaller than a capsule filled w an equivalent amt of powder

v. Enteric-coated tablets

Have delayed-release features

Designed to pass unchanged through the stomach to the intestines

vi. Buccal & sublingual tablets

Flat, oval tab intended to be dissolved in the buccal ouch (buccal tabs) or beneath the tongue (sublingual
tabs)

Bypass gastric degradation

vii. Chewable tablets

Smooth, rapid disintegration when chewed or allowed to dissolve in the mouth, have a creamy base, usually
of specially flavored

viii. Effervescent tablets

Prepared by compressing granular effervescent salts that release gas when in contact with water

“Bubble action” assist breaking up the tabs and enhancing the dissolution of active drug (tartaric acid)

ix. Immediate-release tablets

Designed to disintegrate and release their medication w no special rate-controlling features, such as special
coatings an other techniques

x. Instantly disintegrating or dissolving tablets

Characterized by disintegrating or dissolving in the mouth within 1 min, some within 10 sec

Within approx 15-30 sec; anything slower would not be categorized as rapidly dissolving

xi. Extended-release tablets

AKA controlled-release tablets

Designed to release their medication in a predetermined manner over an extended period

xii. Vaginal tablets

Aka vaginal inserts

xiii. Modified release tablets

>Extended-release tab. >Delayed release tab

Molded Tablets

i. Tablet triturates

Tabs containing small amts of potent drugs

ii. Hypodermic tablets

Originally used by docs in extemporaneous preparation of parenteral solns

Obsolete

iii. Dispensing tablets

Aka compounding tabs

Phs used them to compound

C. PHARMACEUTICAL INGREDIENTS

Active Pharmaceutical ingredients (API)

Excipients

Excipients criteria:

1. They must be non-toxic and acceptable to the regulatory agencies.

2. They must be commercially available in an acceptable grade.

3. Their cost must be acceptably low.

4. They must be physiologically inert.

5. They must be physically and chemically stable.

6. They must be free of any unacceptable microbiologic load.

7. They must be color compatible.

8. Diluents and other excipient must be approved direct to food additives.

9. They must have no deleterious effect on the bioavailability of the drug(s) in the product.

Commonly used excipients in tablet manufacturing

1. Diluents

To improve cohesion and improve qualities of powder blend

Examples:

1. LACTOSE : Hydrous (reacts w/ alkaline so causes Mailard reaction), anhydrous (preferred bc it prevents
Maillard reaction – brown coloration due to alkaline reaction), spray dried (20-25% incorporated for direct
compression)
 2. STARCH : corn, wheat, potatoes

3. MCC microcrystalline cellulose (+acid to cellulose) : Avicel pH-101 (powder) and pH-102 (granules)

4. MANNITOL : Chewable tablets (exhibits excellent flow properties)

5. Others : Dibasic calcium phosphate, Sugar, Sorbitol - sugar substitute, also used in chewable tabs(sugar
alcohol)

2. Binders

Binding force required – ad

Compatibility with other components

Quantity added

Form: soln or dry form

Wet granulation-direct

Dry-incorporate binder

Examples:

SUGAR

Sucrose Liquid glucose

NATURAL BINDERS SYNTHETIC/ SEMISYNTHETIC POLYMER

Acacia Methylcellulose
Tragacanth Ethylcellulose
Gelatin Hydroxypropylmethylcellulose Starch Paste and Polyvinyl Pyrrolidone (PVP) Pregelatinized starch
Alginic acid Polyethylene Glycol (PEG) Cellulose

3. Disintegrants

Promote breaking up for dissolution

Ideal disintegrating time: 15 minutes

Mechanism of Action:

1. May increase the porosity and wettability of the compressed tablet matrix.

-surface active
a. Starch, MCC, Sodium Starch glycolate

2. May operate by swelling in the presence of aqueous fluids

-increase internal pressure by swelling

b. Sodium starch glycolate; croscarmellose sodium; crospovidone; pregelatinised starch

3. Tablet disintegration may also be mediated by the production of gas whenever the tablet contacts aqueous fluids.

-super-disintegratants very fast: 30 secs. Used in low amount 1-5% by wt.

a. Effervescent tablets

Lubricants
Antiadherent, and

Glidants (promote flow of powder within hopper into tab dye.

4. Lubricants:

Reduce friction between dye and tablet

The concentration of lubricant used is an important consideration in the subsequent disintegration and dissolution of
the drug from the tablet.

1. If the concentration is too low:

i. Picking

ii. Sticking

iii. Capping

2. If the concentration is too high:

i. Decrease in tab hardness

ii. Inability to compress into tabs

iii. Decrease in disintegration time and dissolution rate

Classification of lubricants
a. Water Insoluble Lubricants (Hydrophobic)

 -  Most widely used lubricant today.

 -  Good lubricants and usually effective at low concentrations.

 -  May have both anti-adherent and glidant properties.

INSOLUBLE LUBRICANTS

Talc

Waxes

Liquid paraffin Notes:

CONC.

1 -2

1-5

Up to 5

COMMENTS

Insoluble but not hydrophobic Moderately effective.

-----

Dispersion problem Inferior to stearates

Stearates(Magnesium Stearate, Calcium Stearate, Sodium stearate)

Less than 1% bc it is very effective

Reduce tablet strength Prolong disintegration Widely used.

b. Water Soluble Lubricants (Hydrophilic)

--

i.

ii.

iii.

Used when a tablet is completely soluble or when unique disintegration and dissolution time are required. Shows
higher dissolution rate.

PEG

-great amounts are used.

Polyoxyethylene stearates

-Nonionic. 1-2% used

Lauryl sulphate salts

-Anionic

Examples:

1. Magnesium stearate –, most common. Hydrophobic

2. Talc – glidant, lubricant (1-2%). Aka magnesium silicate

3. Colloidal silicon dioxide –glidant (0.2% by wt) aka aerosil, cap o sil, colloidal silica. Very
small particle size adhering to other ingredients

Antiadherents:

Examples:
ANTIADHERENTS %( W/W)

-will not stick to dye

Cornstarch 3–10

Notes:

COMMENT

Lubricant with excellent antiadherents properties

Talc 1–5 Lubricant with excellent antiadherents properties

Stearates < 1 Antiadherents with water insoluble lubricant

Miscellaneous excipients used in the formulation of tablets

1. Adsorbents

-powder must be dry before compression, this is used.

Examples:

i. Magnesium oxide –light and heavy types depends on density. Glidant. Alkaline

ii. Magnesium carbonate – hydrate, basic and anhydrous. Diluent. Alkaline

iii. Kaolin/Bentonite – hydrated aluminum silicate is responsible for their hydrating action (1-2% w/w)

2. Coloring Agents

Certified FD & C OR D& C colorants

Approved and certified by FDA

refer to pic

3. Sweetening Agents

-improve palatability and acceptability. For chewable tabs. Refer to pic!

4. Surface-active Agents

-improve wetability., penetration to gastric, enhancing tab disintegration. For poorly soluble. Must be used
carefully

D. PROCESSES FOR SOLID DOSAGE FORM

- The process of making a compressed tablet requires the drug-excipient mixture to be free-flowing from the hopper
of the tablet press into the die cavities for high speed compression of the powder mix into tablets.

Size reduction, segregation, granulate, tab production.

Diagram: (refer to pic)

The choice of method for the manufacture of tablets is dependent on a number of factors:

i. The physical and chemical stability of the therapeutic agent during the manufacturing process

ii. The availability of the necessary processing equipment

iii. The cost of the manufacturing process

iv. The excipients used to formulate the product.

Powder fluidity:

Hopper into the die

Consistent wt

Mechanically by the use of vibrators, incorporate the glidant

Powder compressibility:

Stable, intact (refer to pic)

Methods used for the manufacture of tablets

i. Wet Granulation

Longer process. Costly.

iii. Direct Compression – for crystalline

Starch, spray dried lactose, microcrystalline cellulose, sugar (specific for direct compression MUTAB)

Advantages:

a. Reduced production cost

b. Improved stability

c. Faster dissolution rate

Disadvantages

a. Tendency of diff particle size promoting segregation which leads to non uniformity

b.

c.

Steps:

a. Die filling

b. Tab formation

c tab ejection

TABLET MANUFACTURING

 -  Tablets are prepared by forcing particles into close proximity to each other by powder compression, which
enables the particles to cohere into porous, solid specimen of defined geometry

 -  The process of tableting can be divided into 3 stages:

1. Die filling (lower punch and upper punch-will descend)

Gravitational flow. Powder is put into die. We may need agitators for those w low fluidity. Hopper to die.

2. Tablet formation

Punching. Max applied force. Force also responsible for disintegration. Maintain tab shape.

3. Tablet ejection

removed from die. Followed by compression. Lower punch and upper punch moves upward to
eject tab after compression.

TYPES OF TABLET PRESSES

1. Single-punch press

Aka eccentric press. Hopper + hopper shoe (guides tab). 200tab/min produced. Time consuming so use is
limited. Circular and oval punches.

2. Rotary press

Aka multistation press. 10,000tab/min. Series of upper and lower punches. Hopper to die – fluidity is
important which is by gravitation. Fill Cam tracks are guiding the punches
E. TABLET COATING

- Coating may be applied to a wide range of oral solid dosage forms, including tablets, capsules, multiparticulates
and drug crystals.

Reasons for coating

1. Protection of the drug (improve stability)

2. Modifying drug release

3. Masking unpleasant taste or odor of drug

4. Aesthetic/ distinction

5. Increase mechanical strength of the product

Types of coating process

1. SUGAR COATING – smooth, rounded, contour, w even color coverage and a glossy finish.

Steps involved:

a. SEALING >shellac>>CAP>PAP(polyvinyl acetate pthalate)

b. SUBCOATING >Calcium carbonate+ sucrose (adds 50-100% to size) (bulking agent to fill rounded tab) > Talc
(anti-adherant) > Acacia (binder to ensure subcoat is efficiently applied. No brittleness) > rough product

c. SMOOTHING > rounding and smoothing. Makes use of sucrose still (5-10 additional coatings)

d. COLORING >visual elegance (Titanium dioxide opaquent whiten) > water-soluble dyes > water-insoluble pigments

e. POLISHING > glossy finish > beeswax and carnauba wax

f. PRINTING > identification processes > edible inks > inkjet and padprinting process

2. FILM COATING > spraying > wetting > recrystallisation > coated particle

 -  Places a thin, skin-tight coating of a plastic-like material over compressed tablet.

 -  Developed to produce coated tablets having essentially the same weight, shape, and size as the originally
compressed

tablet.

Difference of film coating vs sugar coating REFER TO PIC

Types of film coating (based on the intended effect of the applied coating to drug release characteristics.

1. Immediate-release film coating (HPMC – most common film)

1. Non-functional coatings

2. No effect on biopharmaceutical properties

2. Modified-release film coating (methylcellulose, hydrocypropycellulose coats)

1. Functional coatings

2. Delayed-release coatings (enteric coat)

ii. Acid-labile drugs

iii. Gastric irritant drugs

3. Extended-release coatings

i. Insoluble in water

ii. Ensure drug release in consistent manner

FILM-COATING FORMULATIONS

1. Film-formers

a. Immediate-release
i. Cellulose derivatives

1. HPMC( most common;mechanical strength), HPC, and MC

ii. Vinyl derivatives

1. PVP and PVA (polyvinyl alcohol – more commonly used due to good barrier capacities and adheres to tabs)

b. Modified-release
1. Cellulose derivatives

i. Ethyl cellulose and cellulose acetate

2. Methylmethacrylate copolymers and Methacrylic acid copolymers

3. Phthalate esters

i. HPMCP(Hypromellose pthalate), CAP(cellulose acetate pthalate), and PVAP

4. Plasticizers

1. Polyols (PEG)

2. Organic esters (Diethyl phthalate and triethyl phthalate (DEP and TEP)

3. oils/glyceride (coconut oil, castor oil)

5. Opaquants & colorants

1. Iron oxide

2. Titanium dioxide

3. Aluminum lakes

6. Solvents

a. Organic solvents (non aqueous)

Disadvantages

i. Expensive solvents

ii. Release of potentially toxic solvents to atmosphere.

iii. Solvent residue issues. (Portion of solvent is retained in tab. Harmful to px if ingested)
 iv. Safety issues

Advantage

i. Film adheres quickly to tablet surface (volatility of the solvent).

b. Aqueous solvent

Advantages

i. inexpensive
ii. possess no environmental problem

Disadvantages

i. slow evaporation of solvent.

ii. appearance of picking and peeling of film fragments.

iii. tablet coating defects

7. Others

1. Alloying substance (

2. Surfactant

Used for psreading

3. Glossant

Provide luster to our product

Film coating vs. Sugar coating

3. COMPRESSION COATING

Dried probiotic bacteria inside gel-forming coating material

Reasons for compression coating:

1. Tablet core cannot tolerate organic solvent or water and yet needs to be coated for taste masking.

2. To provide delayed or enteric properties to the finished product.

3. Avoid incompatibility by separating incompatible ingredients.

4. Coat is uniform in thickness

5. Less coating material is required

Coating Equipment

1. Standard coating pan (30 deg angle)

1. Pellegrini pan system (buffled pan + air diffuser to dry coating material)
 2. Immersion sword system (sworn inside pan where air can pass through to facilitate drying)

3. Immersion tube system (tube provides color)

2. Perforated pan system

1. Accela-Cota

2. Hi-coater system

3. Glatt coater system

4. Driacoater system

3. Fluidized bed coater

Fluid Bed Technology Processes:

1. Bottom spray (Würster process)

2. Top spray (Granulator process)

3. Tangential spray (Rotor process)

F. TABLET DEFECTS

Problem in tablets are either related to imperfections in any one or more of the following factors:

a. Process related
i. Capping and Lamination – separation of a portion of a tablet. Lamination complete or incomplete
separation (bottom or upper surface 2 or more layers). Capping 1 layer

ii. Cracking - upper and bottom layer. Due to rapid expansion of tab bc of using deeply concave punch

iii. Chipping – portion of tab chips off. Due to mis-set of ejection take off

b. Formulation related

i. Picking and Sticking

ii. Binding

iii. Twinning

iv. Orange peel (inefficiency of the spreading of the color into the tab)

v. Bridging filling the logo in the tab) high percentage of the solids can cause bridging

vi. Erosion – disintegration before it is consumed. Soft tabs. Pan may be turning too fast, over-wetted tab
surface. Inadequate tabs. Lack tab strength.

vii. Blistering – coat blisters and chips off. Local detachment of film from the tab forming a blister. Entrapment of
gases during heating.

viii. Blooming – characterized by the dull appearance. Due low molecular wt ingredients usually the plasticizers

ix. Blushing – whitish specs. Haziness

x. Color variation – dark portion. Higher inetnsity of color. Improper mixing, insufficient coating, spraying
variation

c. Machine related
xi. Double impression – loosely attached punch.
d. Defect related to more than one factor

Xii. Mottling – tiny specs of color variation due to colored API, improper mixing, dirt in granular material, oil spots due
to oily lubricant

G. TABLET PACKAGING

Role of packaging

1. Protection

2. Information

Types of tablet packaging

1. Blister pack > plastic and aluminum > PVC PET PP and LDPE. Thermoform blister. Cold form
blister. Tropicalised blister (more protection)

2. Strip pack – formed by feeding 2 webs of heat sealable flexible film through a heating crimping
roller. The product is dropped into the pocket formed before forming the final set of seals.
Cellophane

3. Bottles. Glass (type II or III). Plastic LDPE HDPE PP

Types of blister pack

1. Thermoform blister

2. Cold form blister

c. Tropicalised blister

2. Strip pack
- Is formed by feeding 2 webs of a heat sealable flexible film through a heating crimping roller. The product is
dropped into

the pocket formed before forming the final set of seals.

3. Bottles

1. Glass
i. Type III (solids)

ii. Type I (parenterals)

2. Plastic
i. Low Density Polyethylene (LDPE)

ii. High Density Polyethylene (HDPE) iii. Polypropylene (PP)

v. Cyclo-olefin Copolymer (COC)

Evaluation of primary packaging materials

1. LEAKAGE TEST

2. HYDROLYTIC RESISTANCE

3. COLLAPSIBILITY
 4. RESIDUE ON IGNITION

5. BUFFERING CAPACITY

6. LIGHT TRANSMISSION

7. WATER VAPOR PERMEATION

8. HEAVY METALS AND NON-VOLATILE RESIDUE

H. QUALITY CONTROL TESTS FOR TABLETS

- In tablet formulation development and during manufacturing of tablets, a number of procedures are used to assess
the quality of the tablets.

1. GENERAL APPEARANCE

i. Size and Shape

ii. Organoleptic Properties

2. DRUG CONTENT AND RELEASE

i. Content Uniformity

ii. Weight Variation test

iii. Tablet Thickness

iv. Disintegration test

v. Dissolution test (Apparatus 1 and 2)

MECHANICAL STRENGTH OF TABLET

i. Friability – tendency of tab to form fragment.

ii. Tablet Hardness