Capsules

Question 1

Why are capsules made?

Answer 1

• drug cannot be compressed via dry granulation.
• drug is sensitive to water so no wet granulation.
• change in the polymorphic form when compressed.
• degrade on compression.

Question 2

What drugs are capsules suitable for?

Answer 2

For drugs which require gastric protection.

Question 3

What two type of capsules are available?

Answer 3

Hard Gelatin Capsules HGC

Soft Gelatin Capsules SGC

Question 4

Describe hard gelatin capsules?

Answer 4

Two-piece system consisting of cap and body.

Has a locking system with indentations on the outside of the body and inside of the cap.

Question 5

Describe how pulsatile drug release capsules work, the Pulsincap system.

Answer 5

Consists of an insoluble body, water-soluble cap and a hydrogel plus made of hydrophilic polymer or lipid.
Plug allows a lag time for release of drug.
When taken, water-soluble cap dissolves, hydrogel plug when exposed to aqueous environment, absorbs water and expands. Results in ejection of drug from capsule body.

Question 6

Explain how dual-drug capsule systems work?

Answer 6

Two drugs are placed in a capsule. Drug A placed in the in the cap and drug B placed between body and plug. Water-soluble cap dissolves, drug A released. Plus absorbs water and expand, Drug B released.

Question 7

Describe how osmotic systems for capsules work?

Answer 7

The capsule is coated with a osmotically active semi-permeable membrane. Capsule contains drug formulations. On exposure to water, water is drawn into osmotically active layer, expands and drug is pushed out of capsule.

Question 8

How is gelatin made?

Answer 8

By hydrolysis of collagen

- collagen from animal skin, bones and white connective tissue.

Question 9

Describe gelatin.

Answer 9

It is a heterogenous mixture of single or multi-stranded polypeptides.
Stable when dry but susceptible to microbial degradation on exposure to moisture.
Naturally contains 13-16% moisture.
Alternatives are hydroxypropyl methylcellulose (HPMC) or starch hydrolysate (vegetarians).

Question 10

Why is gelatin used?

Answer 10

• non-toxic and safe
• soluble in biological fluids at body temperature
• conc (40%w/w) solutions of gelatin are mobile liquids about 45 degrees
• manipulated by temperature
• undergoes liquid to gel transition when cooled

Question 11

The grade of gelatin is characterised by bloom strength. What is this?

Answer 11

A measure of gel-rigidity.
Specifically the cohesive strength of cross-linkages between molecules.
- defines as load per weight in grams.
(high bloom strength = harder material and viscous in solution)

Question 12

What is the function of 6 dimples of the capsule?

Answer 12

Provides a pre-lock.

Question 13

Describe the features of Coni-Snap.

Answer 13

 Tapered rim to aid closure
 Air vents allow air to escape
 Six dimples to provide pre-lock
 Closely-matched locking rings

Question 14

Describe feature of Db-cap.

Answer 14

• Has a larger diameter and shorter length.
• The cap covers most of the body; impossible to hold the body and open without crushing it.
• Provides increased security of the contents.

Question 15

What are the two sealing methods for hard gelatin capsules filled with liquids?

Answer 15

• gelatin band sealing

- hydro-alcoholic solvent seal

Question 16

Why use liquids or semi-solids to fill HGCs?

Answer 16

 Powder flow problems avoided
 Avoidance of airborne particles
 Improved fill weight accuracy
 Convenient for formulations with a 
low melting point (oils, etc.)
 Can improve solubility and absorption
 Low dose/high potency drugs

Question 17

What type of liquids can be filled into capsules?

Answer 17

Non-aqueous liquids.

Question 18

What type of semi-solids can be filled into capsules?

Answer 18

Thermo-softening mixtures.
Thixotropic mixtures - low visc on mixing/shearing, high visc when shearing ceases.
Pastes.

Question 19

How are HGCs filled with semi-solids or liquids?

How does the piston work?

Answer 19

Piston filling

• volumetric dosing device
• prevents leakage
• semi-solids are filled in the liquid state if possible - after filling these revert to original state
• As piston moves left, it draws liquid in, when piston moves right, liquid leaves nozzle and can fill capsule.

Question 20

How does viscosity affect variability of fill volume to capsules?

Answer 20

Low viscosity = mixture can splash from capsule during filling causing loss of product
High viscosity = difficult to transfer mixture from nozzle of filling device to capsule body

Question 21

What is the suitable viscosities acceptable for filling HGCs?

Answer 21

0.1-20 Pa.s (Pascal seconds)

Question 22

What is EMC?

Answer 22

Equilibrium Moisture Content

- moisture content when capsule is left to equilibrate with its liquid filling

Question 23

What is an issue with using PEG <1000 as an excipient for drug added to capsules?

Answer 23

Absorbs water from the capsules resulting in moisture loss and brittleness.

Question 24

What are the plasticisers soft gel capsules made of?

Answer 24

Glycerol
Propylene glycol
Sorbitol

Question 25

What is the benefit of using SGCs?

Answer 25

Soft gelatin capsules can provide the improved dissolution associated with liquids, whilst retaining the convenience of a solid dosage form.

Question 26

What does a plasticiser do?

Answer 26

Plasticiser allows the polymer chains to slide, making the polymer more flexible.

Question 27

What are dyes?

Answer 27

Dyes are defined as intensely coloured organic substances that impart colour to a substrate by selective absorption of light.
-dyes are used in their water soluble form

Question 28

What are opacifiers?

Answer 28

e. g. titanium dioxide

- these protect from light and conceal capsule contents.

Question 29

What are pigments?

Answer 29

Pigments are defined as coloured particulate organic or inorganic solids which are usually insoluble in the
substrate. They alter appearance by selective absorption and/or scattering of light.

Question 30

What are two preservatives used in manufacture of HGCs and SGCs?

Answer 30

• esters of p-hydroxybenzoic acid (p-hydroxybenzoate = methyl paraben and propylhydroxybenzoate = propylparaben)
• sulpher dioxide