Tablets and Capsules

 

⭐ TABLET DOSAGE FORM – FORMULATION NOTES

1. Definition (Lachman & Mehta)

A tablet is a solid unit dosage form containing one or more medicaments with or without excipients, obtained by compression or molding.

Key features:
✔ Accurate dose
✔ Most stable dosage form
✔ Easy to administer & mass-produce
✔ Good patient compliance

2. Advantages & Disadvantages (Lachman)

✔ Advantages

• Accuracy & uniformity of dose
• Lower production cost
• Compact, stable, portable
• Coating improves aesthetics & compliance
• Modified release possible

✘ Disadvantages

• Poor wetting or slow dissolution (problem for poorly soluble drugs)
• Compression issues for high-dose drugs
• Bioavailability affected by GI conditions and excipients
• Not suitable for unconscious patients and those with dysphagia

3. Types of Tablets (Lachman, RM Mehta)

A. By Route

• Oral tablets: compressed, film-coated, sugar-coated, enteric-coated, chewable, dispersible, effervescent, buccal, sublingual, ODT
• Parenteral: implantation tablets
• Vaginal: vaginal tablets/pessaries

B. By Release Pattern

• Immediate release (IR)
• Modified release (sustained/controlled/extended)
• Delayed release (enteric)
• Targeted release

Mnemonics: "COFFEE BEDS"
C – Chewable
O – ODT
F – Film-coated
F – Fast dissolving
E – Effervescent
E – Enteric
B – Buccal
E – Extended release
D – Delayed
S – Sublingual

4. Tablet Formulation Components (Excipients)

(Lachman, Mehta, Brahmankar)

Tablets = API + Excipients
Excipients ensure compressibility, flow, stability, palatability, disintegration, dissolution.

⭐ 4.1 Excipients Classification

1. Diluents / Fillers

Used when API dose is small.

Examples:

• Lactose (monohydrate, spray-dried)
• MCC (Avicel PH101/102)
• Dicalcium phosphate (DCP)
• Mannitol (chewables)
• Starch

✔ Properties: good compressibility, non-reactive
✘ DCP: Non-hygroscopic, but insoluble → slower dissolution

2. Binders / Granulating Agents

Improve cohesiveness during compression.

Examples:

• PVP (Povidone)
• HPMC
• Starch paste (10–20%)
• Gelatin solution
• Sucrose syrup

3. Disintegrants

Help breakup of tablet upon contact with fluids.

Superdisintegrants:

• CrosPovidone (CP)
• Croscarmellose sodium (CCS)
• Sodium starch glycolate (SSG)

Mechanisms:
✔ Swelling
✔ Porosity wicking
✔ Deformation recovery

4. Lubricants

Reduce friction between tablet and die wall.

Examples:

• Magnesium stearate
• Stearic acid
• Sodium stearyl fumarate

Over-lubrication → ↓ hardness, ↓ dissolution (important MCQ).

5. Glidants

Improve flow of powder during compression.

Examples:

• Colloidal silicon dioxide
• Talc

6. Anti-adherents

Prevent sticking to punch faces.

Examples: talc, starch

7. Colorants, Flavors, Sweeteners

• Colors: FDA certified lakes
• Flavors: mint, fruit
• Sweeteners: aspartame, saccharin, sorbitol

5. Tablet Manufacturing Processes (Lachman)

There are 3 core methods:

⭐ 5.1 Direct Compression (DC)

Drug + Excipients → Blend → Compress

✔ Requirements

• API must have good compressibility + flow
• Use DC grades (e.g., spray-dried lactose, MCC)

✔ Advantages

• Simple, fewer steps
• Faster, cost-effective
• Moisture/heat-sensitive drugs

✘ Disadvantages

• Not suitable for low-dose or poorly compressible drugs

⭐ 5.2 Dry Granulation

Two methods:

• Slugging (using large tablets)
• Roller Compaction →

Drug + Excipients → Slug/Roll compact → Milling → Lubrication → Compress

Used for:

• Moisture/heat-sensitive drugs
• Poorly compressible API

⭐ 5.3 Wet Granulation

Drug + Binder → Wet Mass → Screen → Drying → Sizing → Lubrication → Compression

✔ Advantages

• Good flow, compressibility
• Minimizes segregation
• Suitable for low-dose drugs

✘ Disadvantages

• Costly, time consuming
• Not suitable for moisture/heat-sensitive drugs

6. Tablet Defects (Lachman, RM Mehta)

During Compression

• Capping — top part separates
• Lamination — layers form
• Cracking — improper moisture, too much pressure
• Sticking — granules stick to punches
• Picking — material sticks in engraving
• Chipping — small breakage at edges
• Mottling — color variation

Mnemonics: "CLCS CPM"

C – Capping
L – Lamination
C – Cracking
S – Sticking
C – Chipping
P – Picking
M – Mottling

7. Evaluation of Tablets (Pre- & Post-compression)

⭐ 7.1 Pre-compression Tests

• Angle of repose
• Bulk density
• Tapped density
• Carr’s index
• Hausner ratio
• Particle size analysis
• Moisture content

⭐ 7.2 Post-compression Tests

1. Weight Variation Test (IP/BP/USP)

For ≥ 25 mg drug or 25% of tablet weight.

Limits:
± 5%: >250 mg
± 7.5%: 130–250 mg
± 10%: <130 mg

2. Hardness Test

Ideal: 4–10 kg/cm²

3. Friability

≤ 1% acceptable

4. Thickness & Diameter

5. Disintegration

Uncoated tablets: <15 minutes (IP)
Enteric-coated: No disintegration in 0.1 N HCl for 2 h

6. Dissolution

USP Apparatus I/II
Q = amount dissolved in fixed time (e.g., Q = 80% in 30 min)

7. Assay & Content Uniformity

8. Factors Affecting Tablet Bioavailability

(Brahmankar & Wolters Kluwer)

Formulation factors:

• Disintegration time
• Dissolution rate
• Particle size
• Polymorphism
• Excipients (lubricant level, binder type)
• Compression force (↑ force → slow dissolution)

Drug factors:

• Solubility, Log P
• pKa
• Stability in GI fluids
• First-pass metabolism

9. Special Tablets

Enteric-coated tablets

Coating polymers:

• Cellulose acetate phthalate (CAP)
• HPMC phthalate
• Shellac

Sustained-release tablets

Mechanisms:

• Matrix (HPMC, EC)
• Osmotic pumps (OROS)
• Coated systems
• Ion exchange resins

10. Tablet Packaging

• Blister packs (PVC, PVDC)
• Strip packaging
• Bottles (HDPE with desiccants)

11. Flowchart: Tablet Formulation (Exam Direct)

API → Preformulation → Choice of Method (DC/Wet/DRG) 

→ Excipients selection → Granulation → Drying 

→ Sizing → Blending → Lubrication 

→ Compression → Coating (optional) 

→ Evaluation → Packaging

⭐ MNEMONICS (High-yield for exams)

Excipients order (Typical):

"D-B-D-L-G-A-C"
D – Diluent
B – Binder
D – Disintegrant
L – Lubricant
G – Glidant
A – Anti-adherent
C – Color/flavor

Tablet Defects: “CLCS CPM”

C – Capping
L – Lamination
C – Cracking
S – Sticking
C – Chipping
P – Picking
M – Mottling

Superdisintegrants: “3 Cs + S”

CCS – Croscarmellose
CP – Crospovidone
SSG – Sodium starch glycolate

 

⭐ CAPSULE DOSAGE FORM – COMPLETE NOTES

1. Definition (Lachman, Mehta)

A capsule is a solid unit dosage form in which drug substances are enclosed within either a hard or soft soluble container or shell, usually made of gelatin.

✔ Used for solids, semisolids, liquids (in soft-gel), pellets, microgranules
✔ Capsule masks taste/odor and offers flexibility in formulation

2. Advantages & Disadvantages

⭐ Advantages

• Good patient acceptability
• Masks unpleasant taste/odor
• Better bioavailability than tablets (less compression)
• Can fill powders, pellets, small tablets, liquids (SGC)
• Elegant appearance
• Easy to formulate and customize dose
• Protects sensitive drugs (light-, moisture-sensitive)

✘ Disadvantages

• Costlier than tablets
• Hygroscopic, moisture-sensitive APIs incompatible with gelatin
• Capsule shells become brittle in < 35% RH
• Not suitable for children and dysphagic patients
• Risk of tampering (requires sealing)

3. Types of Capsules

A. Hard Gelatin Capsules (HGC)

Shell components:

• Gelatin (80–85%)
• Water (10–15%)
• Dyes/pigments
• Opacifiers (titanium dioxide)
• Preservatives (rare)
• Plasticizers (small amounts)

Grade: Type A (acid-treated collagen) or Type B (alkali-treated collagen)

Designs:

• Cap + Body → friction fit
• Snap-fit (IMPROVES LOCK)
• Coni-snap (tapered body for easy filling)

B. Soft Gelatin Capsules (SGC)

Shell composition:

• Gelatin
• Plasticizers (glycerin, sorbitol)
• Water
• Preservatives
• Colorants, opacifiers

Used for:
✔ Oils, hydrophobic liquids
✔ Suspensions
✔ Self-emulsifying drug systems
✔ Vitamins, essential oils

C. Special Capsules

• Enteric-coated capsules
• Sustained-release capsules
• Liquid-filled HPMC capsules
• DRcaps (delayed-release)
• Inhalation capsules (Rotacaps)
• Sprinkle capsules (pellets inside)

⭐ 4. Capsule Sizes (Lachman)

For human use: Sizes 000, 00, 0, 1, 2, 3, 4, 5.

Size	Capacity (mg for moderately dense powder)
000	1000 mg
00	600–800 mg
0	400–500 mg
1	300–400 mg
2	200–300 mg
3	150–200 mg
4	120–150 mg
5	60–100 mg

⭐ Mnemonic: “Big → Small: 000 to 5”
⭐ Size 0 is most commonly used in industry

5. Formulation of Hard Gelatin Capsules

⭐ 5.1 Ingredients added to the capsule contents

Based on Lachman (Industrial Pharmacy) and RM Mehta.

A. Diluents/Fillers

Used to increase bulk when API dose is low.
Examples:

• Lactose (monohydrate)
• MCC
• Starch
• Dicalcium phosphate
• Mannitol (chewables)

B. Glidants

Improve flow into capsule body.

• Colloidal silicon dioxide
• Talc

C. Lubricants (for powder flow, not die lubrication)

• Magnesium stearate
• Stearic acid

D. Wetting agents

For poorly wetting drugs (e.g., hydrophobic APIs)

• Sodium lauryl sulfate (SLS)

E. Disintegrants

If capsule releases pellets/tablets inside

• Croscarmellose sodium
• SSG
• Crospovidone

⭐ 6. Capsule Manufacturing & Filling (HGC)

6.1 HGC Shell Manufacturing (Lachman)

Dip-coating process:

1. Stainless steel mould pins dipped in gelatin solution
2. Rotated → uniform coating
3. Dried in controlled humidity
4. Stripped off
5. Trimmed
6. Cap & body joined
7. Sorted by size & defects

6.2 Filling Operations

Methods:

A. Hand filling (hand filling machine)

Used in pharm labs and small-scale.

B. Semi-automatic machines

Parts: rectification → separation → filling → joining → ejection

C. Automatic capsule filling machines

Filling types:

• Powder plug method
• Dosator-nozzle method
• Tamping pin method
• Auger filling (for cohesive powders)
• Pellet filling
• Tablet filling
• Liquid/semi-solid filling (special capsules)

⭐ 7. Soft Gelatin Capsule Filling (SGC)

Fill material must be:
✔ Non-aqueous
✔ Compatible with gelatin
✔ Low water activity

Examples:

• Vegetable oils
• PEG-based liquids
• Self-emulsifying drug delivery systems (SEDDS)
• Vitamins (A, D, E, K)

SGC Manufacturing:

Rotary die process
→ Two gelatin ribbons
→ Formed + filled + sealed in a single operation

8. Capsule Sealing

Used to prevent tampering & leakage.

Types:

• Band sealing (gelatin band)
• Heat welding
• Liquid sealing (hydroalcoholic glue)

9. Capsule Stability Issues

Gelatin absorbs moisture → shell softening
Low humidity → shell becomes brittle
Ideal RH: 35–45%
Stored in well-closed containers with desiccants.

10. Incompatibilities

Capsule shells incompatible with:

• Highly hygroscopic materials
• Efflorescent powders
• Volatile solvents
• Strong alkaline materials

Solutions:
✔ Use HPMC capsules
✔ Use double-shell capsules
✔ Seal capsules

⭐ 11. Capsule Evaluation Tests

A. Physicochemical Tests

• Appearance & defects
• Weight variation
• Lock integrity
• Moisture permeability
• Shell thickness (SGC)

B. Disintegration Test

Uncoated capsules: <30 min (IP)
Enteric-coated: No disintegration in acid for 2 h, then disintegrates in buffer.

C. Dissolution

Same as tablets: USP I/II
Pellets inside capsules have modified dissolution profiles.

D. Content Uniformity

Required for low-dose drugs.

E. Microbial tests

Applicable for SGC (higher moisture).

12. Bioavailability Considerations (Brahmankar)

Capsules often show faster disintegration and better bioavailability than compressed tablets.

Factors affecting BA:

• Shell dissolution rate
• Pellet size
• Lubricant levels
• Liquid-based fills show enhanced BA

⭐ 13. Capsule Defects (Important for DI Exam)

1. Brittleness

Low moisture content
→ Shell cracks

2. Softening & Stickiness

High humidity
→ Shell absorbs moisture

3. Splits & Fractures

During filling or handling

4. Dented/Deformed capsules

Due to machine impact or poor drying

5. Leakage in SGCs

Improper sealing or formulation incompatibility

⭐ 14. Flowchart – Capsule Formulation (Exam Direct)

API → Preformulation → Selection of capsule type (HGC/SGC) 

→ Excipient selection → Filling → Sealing (if needed) 

→ Evaluation (weight, disintegration, dissolution) 

→ Packaging (blisters/bottles with desiccants)

⭐ High-Yield Mnemonics

Capsule Shell Composition (HGC)

“G-WOP”
G – Gelatin
W – Water
O – Opacifiers
P – Pigments

SGC Components

“GPP-WC”
G – Gelatin
P – Plasticizer
P – Preservative
W – Water
C – Colorant

Filling Methods

“P-D-T-A”
P – Plug method
D – Dosator
T – Tamping pin
A – Auger

Capsule Defects

“BSSDL”
B – Brittle
S – Softened
S – Splits
D – Dented
L – Leaking