CHAPTER 7: CAPSULES

I. Introduction
Enteric coated
- Pass through stomach
Extended release
- Prolonged release
Sublingual/Buccal
- Dissolve under tongue/ in mouth
CAPSULES are solid dosage form enclosed in a small
piece of gelatin
a. SOFT GELATIN CAPSULES
b. HARD GELATIN CAPSULES
II. Hard Gelatin Capsules
Composition:
Gelatin, Sugar Water
Colorant: FD&C And D&C
Opaquant: Titanium Dioxide
13%-16% Moisture content
Content uniformity and weight variation
A. Gelatin is obtained by partial hydrolysis of collagen
obtained from the skin, white CT and bones of animals
- Stable in air when dry but prone to microbial
decomposition when moist distorted when exposed to
higher moisture brittle in extreme dryness
SOLUTION: DESSICANT
- Prolonged exposure to high humidity can affect
vitro capsule dissolution
As observed in
Tetracycline
Chloramphenicol
Nitrofurantoin
- Possible substitute: Cellulose polymers
- Gelatin is insoluble, but SOFTENS in cold
water, SOLUBLE in hot water, SOLUBLE in
warm gastrointestinal fluid
- Gelatin is a protein digested by proteolytic
enzymes
B. Tracking passage of Capsules
1. Scintigraphy

- Gamma ray emitting radiotracer in the

formula + Gamma camera

For drugs of lower dose or when small particles are

required, micronization is employed = 1-20mm

2. Pharmacoscintographic Evaluation
- Transit & Rate of drug absorption
- Effective in:
Vitro & Vivo bioavailability
Integrity & transit time
Drug dosage form
evaluation
3. Heidelburg Capsule
- No. 0 Gelatin capsule size
- Measure gastric pH

Powder mix/Granules should be free flowing

- Addition of lubricant/ Glidant
o Fumed silicon Dioxide
o Magnesium Stearate: water proof
characteristics Retard penetration by
GI, delay dissolution Surface active
agent (Sodium Lauryl Suldate) is used by
wetting GI Fluid
o Calcium Stearate
o Stearic Acid
o Talc
Gelatin capsules are unsuitable for aqueous liquids
because water softens gelatin

C. Manufacturing of Hard Gelatin Capsules

The shells are produced industrially by the
mechanical dipping of pins/pegs Made of Manganese
Bronze, into reservoir of gelatin mixture
How to prepare distinctive looking capsules:
1. Tapering end of the body
2. Tapering both ends
3. Snap fit: Locking grooves
4. Coni Snap: Rim of body is not straight
5. Coni Snap Supro: Upper capsule
extends so far that only the rounded edge of the latter is
visible
D. Capsule Size
000-5 (Largest-Smallest) 65mg-1g
E. Developing Formulation and Capsule Size
Diluent/Filler: produce proper volume & cohesion
Lactose
Microcrystalline
Cellulose
Starch
Disintegrants: Assist break up and distribution in the
stomach ; To achieve uniform drug distribution, density
and particle size should be similar
Progelatinized starch
Croscarmellose
Sodium starch glyconate

Eutectic mixtures may be mixed with absorbents

Magnesium Carbonate
Light Magnesium Oxide
Kaolin
F. Filling hard capsule shells
1. Punch Method
2. Hand operated filling machine
24-300 caps
G. Capsule Sealing
Seal with colored bands
Heat welding process
Liquid wetting agent
III. Soft Gelatin Capsules
Composition:
Gelatin
Glycerin / Polyhydric Alcohol (Sorbitol)
Preservative
Methylparaben
Propyl PAraben
Opaquants
A. Preparation
1. Plate Process
- Using set of molds
2. Rotary Die process
- 1933, Robert Scherer

3. Reciprocating Die Process

B. Uses
Water immiscible and non volatile liquid
Vegetable & Aromatic oil
Aromatic and Aliphatic hydrocarbons
Chlorinated hydrocarbons
Ethers
Esters
Alcohol
Organic Acids
Water miscible non volatile liquids
Polyethylene glycol
Nonionic surface active agents
Polysorbate80
Water miscible non volatile compounds
Propylene glycol
Isopropyl alcohol

NOTE: Water above 5%, alcohol, ketone, acid, amine,

esters are not allowed

disintegrate completely into soft mass with no palpably

firm core

IV. Requirement for capsules

A. Added Substance
Harmless in quantities used
Do not exceed minimum amount required to
provide for effect
Do not impair bioavailability
Do not interfere with requisite compendial assays
and tests.

B. Container: Tight well closed, light resistant

D. Dissolution Test

C. Disintegration Test
Capsules are placed in basket rack assembly,
which is immersed 30x per minute into a
thermostatically fluid at 37C Capsule must

E. Content Uniformity
85% - 115% of label claim for 9/10 dosage unit
F. Oral Administration
Esophageal ulceration occur during dry ingestion
Alendronate Sodium Tablet
6oz-8oz water upon rising in the
morning
Half an hour before food/beverage
Atorvastatin
Should not be administred with grapefruit
juice because it inhibits CYP 34A
isoenzyme Higher plasma concentration