TOPIC 6: HARD AND SOFT GELATIN CAPSULES

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

1. Discuss the different type and use of pharmaceutical capsules.
2. Classify the different pharmaceutical ingredients used in the manufacture of capsules.
3. Describe the following:
i. Methods used for the manufacture of capsules.
ii. Capsule filling
4. Determine the appropriate capsule size for a specific formulation.

A. WHAT ARE CAPSULES?

Advantages of Capsules
a. Capsules avoids many unit operations

b. Increase the oral bioavailability of poorly soluble therapeutic agents

c. Ease of swallowing

d. Difficult to counterfeit

e. Stability

Disadvantages of Capsules
a. The requirement for specialized manufacturing equipment.
b. Potential stability problems associated with capsules containing liquid fills.
c. Problems regarding the homogeneity of fill weight and content may be associated with capsule formulations.

B. RAW MATERIALS
Similar raw materials have been used in the manufacture of both types of capsule. Traditionally both contains:
1. Gelatin Water is the plasticizer for gelatin capsule
- Is a mixture of proteins that is extracted from animal collagen by either partial acid or partial alkaline hydrolysis.
- A measure of relevance cohesive strength of gelatin film
- Bloom strength: is defined as the weight (in grams) required to push a standard plunger 4 mm into the gel.6/6% w/w
Measure of its rigidity, sturdiness
Typa A: skin 7-10 days Pork skin
Type B: Bones, 10x longer hydrolysis

- Viscosity
Single most important factor controlling shell thickness 100 mcm
SGC -150g

Properties of Gelatin
a. Non-toxic.
b. Soluble in biological fluids at body temperature.
c. It is a good film-forming material.
d. Solutions of high concentration, 40% w/v, are mobile at 50°C.

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 e. A solution in water changes from a sol to a gel at a temperature only a few degrees above ambient.

2. Colorants for identification and

a. Water-soluble dyes
1. Azo dyes: -N=N- linkage
2. Non-azo class
a. erythrosine
b. indigo carmine
c. quinoline yellow
b. Insoluble pigments
1. Iron oxides (black, red and yellow)
2. Titanium dioxide (white)

3. Process Aids
a. Wetting agent
SLS sodium lauryl sulfate .15%
Aids in disintegration
Enhance spreading

b. Preservative
Sulfur dioxide .15%
Not a concern for hard gel cap (13-16% moisture content is low)

C. HARD GELATIN CAPSULE

- Dry, powdered ingredients or miniature pellets. It is composed of two halves, termed the cap and the body.
- Capsule shell
o Gelatin blends
o Certified dyes/Opacifiers
o Preservatives
- Innovation: A recent innovation in capsule shell design is the Snap-Fit, Coni-Snap, and Coni Snap Supro hard gelatin
capsules.
- Moisture content: 13 to 16% w/v
- Capacity: 65mg – 1g powdered material
- Capsule sizes: 5(smallest) – 000 (largest)

CONI SNAP
Locking rings for leak-free closure

High humidity
Softening, deformation
Extreme dryness / low humidity
Brittle, crumble shell

Manufacture of hard gelatin capsule shell

35-45% gelatin
a. Dipping of pins
Pins – desired shape of the cap. Maintain temperature 35-35 dg Cfor molding
SLS facilitates spreading
b. Spinning

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 For the removal of bubbles
c. Drying
Required humidity is maintained for moisture content

d. Stripping
Removal of shells from the pins
e. Trimming
Cuts excess portions of the shells
f. Joining
Cap + body

g. Sorting
h. Imprinting

Capsule filling
a. Capsule sizes

Amount of diluent to attain size

000 – largest. 0-4 for average humans. 5 – smallest.

b. Capsule shell filling

Diluents to atain desired size
Must not react w gelatin e.g formaldehyde – causes cross-linking w gelatin – insolubility follows
Must not contain a high-level of “free moisture”
The vol of unit must not exceed the sizes caps available

Limitations in properties of materials for filling into capsules

a. Must not react with gelatin

b. Must not contain a high level of ‘free moisture’

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 Capsule capacity chart 👇
Powder Vol x Tapped Dens
Pellets Vol x bulk dens
Liquids V x Specific gravity x 0.9
c. The volume of the unit must not exceed the sizes of capsule available.

Filling of Hard Gelatin Capsule

1. Aligning and Rectification
2. Opening and separation
3. Filling of powders, granules, pellets, etc.
4. Joining and closing
5. Discharge

Types of material for filling into hard gelatin capsules.

1. Dry solids: powders, pellets (modified release), granulesMR, and tabletsMR
2. Semi-solid: thixotropic mixtures, pastes
3. Liquids: non-aqueous liquids.

Preparation of filled hard gelatin capsules

1. Developing and preparing the formulation and selecting the capsule size
2. Filling the capsule shells
3. Capsule sealing (optional)
4. Cleaning and polishing the filled capsules

Sealing of hard gelatin capsules may also be performed using two further methods:
1. Gelatin band sealing

2. Hydroalcoholic solvent seal

3. Tamper resistance/tamper evidence

Prevents inadvertent separation on handling
Makes sealing semi-solid or liquid caps possible
Excellent barriers to oxygen gas

Capsule filling machines

Principles are the same but filling method is different
1. Bench-scale filling 50,000-10,000 caps in a day
a. FETON (Belgium)
b. LABOCAPS (Denmark)
2. Industrial-scale filling
Semi-full>5,000-150,0000/hr

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 a. Dependent dosing system
i. Auger
Screw type movement agitator to guide powder downward
b. Independent dosing system – for semi or automatic dosing device to weigh powder
Accurate filling but some portions may be vacated
i. Dosator
ii. Tamping finger and dosing disc

Design of hard gelatin capsule formulations for powder fill

FIRMULATION Basic requirements:

1. Must be capable of being filled uniformly.
2. Must release their API for absorption.
3. Must comply with the requirements of regulatory authorities.

Factors in powder formulation

1. Good flow – free flowing, diluent, glidant
2. No adhesion - lubricant
3. Good cohesion – needed to form a plug during dosing

Powder formulation
1. API : dose of the drug and its solubility
2. Fillers : reproducibility of dose, flow, compressibility, dose of medicament and capsule size
: Starch, lactose and MCC
3. Glidants : fluidity of formulation. Cohesion, clumping
: Colloidal silicas, cornstarch, talc, and magnesium stearate.
4. Lubricants : dosing-metal-powder adhesion. Magnesium stearate, calcium stea- rate, and stearic acid
5. Surfactant : wetting of powder mass and enhance drug dissolution

D. SOFT GELATIN CAPSULE

- One piece hermetically, sealed soft gelatin shells containing a liquid, a suspension, or a semisolid.
Soft cap elastic
-oils, oblong shaped

Capsule shell:
a. GELATIN
b. PLASTICIZER
- glycerol, sorbitol and propylene glycol
c. WATER
d. PRESERVATIVE, COLORING, AND OPACIFYING AGENT

Moisture content: 6 – 10% moisture content

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Advantages of Soft gelatin capsules
a. Improved drug absorption and bioavailability

b. Consumer compliance and preference

c. Avoids dust handling problems during manufacture

d. API-Oils ad low melting point drugs 70C

e. Dose uniformity for low-dose drugs.

f. Good product stability

Disadvantages of Soft gelatin capsules

a. Soft gelatin capsules are not easily prepared except on a large scale and with specialized equipment.

b. They are an expensive dosage form.

c. There is a more intimate contact between the shell and its liquid contents than exists with dry-filled hard gelatin capsules.

Drug delivery systems of Soft gelatin capsules

a. Oral softgels

b. Chewable softgels

c. Suckable softgels

d. Twist-off softgels

e. Meltable softgels

Manufacture of Soft gelatin capsule

1. PLATE PROCESS
Sealing lf gelatin film betw pair of dies w fill pocket

2. ROTARY DIE PROCESS

Fill flow by gravity

3. ACCOGEL PROCESS
STERN

ROTARY DIE PROCESS BY ROBERT SCHERER 1933 – Heat sealing

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 Formulation of Soft gelatin capsules
1. GELATIN
Type B(40%). Type A. Sometimes, instead of gelatin we used Vegicaps seaweed, gluten-free stach

2. PLASTICIZER
a. 20-30% less would result to brittle, more-tacky, too flexible
b. GLYCEROL, sorbitol and propylene glycol

3. WATER
a. 30 – 40% of the wet gel formulation
b. 5 – 8%

4. COLORANTS /OPACIFIERS

Soluble dyes or insol pigments or lakes. Titanium dioxide opaque shell

5. PROCESS AID
a. PRESERVATIVE

Types of softgel fill matrices

a. Lipophilic liquids / oils
Soya

b. Hydrophilic liquids
High mw peg400

c. Self-emulsifying oils
*nonionic surfactant, poleoxyethylene sorbitan monooleate

d. Microemulsion and nanoemulsion systems

Submicron. 100nm.

e. Suspensions

Evaluation of Capsules
1. PHYSICAL APPEARANCE
2. WEIGHT VARIATION
3. CONTENT UNIFORMITY
4. DISINTEGRATION TEST
5. DISSOLUTION TEST
6. LEAKING TEST for semi-solid and liquid ingredients from soft capsules

REVIEW (for next meeting discussion)

a. Advantages and disadvantages of pharmaceutical solutions for oral administration
b. How to enhance the solubility of therapeutic agents?

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c. What is the role of micelles for the solubilization of lipophilic therapeutic agents
d. What are the types of pharmaceutical solutions
NAME: ______________________________________________ SCHEDULE: _________________________

ASSIGNMENT

Piroxicam drug has low solubility. For experimental use, HGC (powder weight of 300 mg) of 20 mg dose being made using a blend of
75% lactose anhydrous and 25% MCC and stearic acid (2mg/cap). If the final powder has a tapped density of 0.62g/cm3, select a
capsule size and calculate the amount of each ingredient needed in making a batch of 50 capsules.

Solution:

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NAME: ______________________________________________ SCHEDULE: _________________________

ACTIVITY

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