Capsules

Question 1

Why are capsules less commonly manufactured in comparison to tablets?

Answer 1

Much more complex process to manufacture capsules as two manufacturers are required (one for the shell, one for the powder).
More expensive as more machinery is required, more people therefore profit isn’t as great.

Question 2

For which types of materials is capsule form required?

Answer 2

Used for materials that:
Degrade on compression
Are water sensitive and not easily dry granulated
Easily change polymorphic form

Question 3

How does capsule sizing work?

Answer 3

Capsules come in 8 different sizes.

The smallest lengthened capsule is size 5 (0.13ml) and the longest in size 000.

Question 4

What are capsule shells made from?

Answer 4

The shells are made from gelatin. Nowdays not all capsule shells are made from gelatin and there are more vegan options.

Question 5

How is gelatin made?

Answer 5

Hydrolysis of collagen which is derived from protein in animal connective tissues.

Question 6

What determines whether something is a hard capsules or whether it is a soft capsule?

Answer 6

The bloom scale determines whether a capsule is classified as soft or hard.
Essentially a plunger is put into the gelatin of 6.66% and how much force is required to move the piston a set distance determines if it is a soft (low bloom strength) or hard capsule (high bloom strength).

Question 7

What are the types of colourants used for hard shell capsules?

Answer 7

Insoluble pigments - this includes titanium dioxide (white) and iron oxides (black, red or yellow).

Soluble dyes- azo or non-azo, erythrosine (pink), indigo carmine and quinoline yellow.

Question 8

How does the protein percentage compare for hard shell capsules and soft shell capsules?

Answer 8

In hard shell gelatin capsules it is roughly 84-90% protein whereas in soft shell capsules it is 40-50% in soft shelled capsules.

Question 9

Describe the manufacturing process of hard shell capsules.

Answer 9

Firstly pins are dipped into a gelatin solution of desired viscosity.
The rotating spinner, rotates the pins so that they now face upwards, this allows the gelatin solution to be evenly distributed across the cap (uniform gelatin layer).
The pins then enter the drying chamber before the gelatin is stripped from the pins.
The caps are then trimmed down and then the cap and body of the capsules are joined.

Question 10

6 stages of hard shell manufacturing?

Answer 10

Dipping
Spinning 
Drying
Stripping
Trimming
Joining

Question 11

Describe the method of powder filling of capsules for bench scale production.

Answer 11

Empty shelled capsules are placed in the loading tray with the caps facing upwards. The loading tray is placing onto the bed.
The CAM handle is moved separating the body from the cap. The loading tray is then removed from the bed leaving the empty body of the capsules facing upwards. These are then dipped into the bed.
Powder is then evenly distributed into the empty body of capsules. Powder tray is removed.
Pins are pressed down into the body of the capsules, pressing the powder down. Uplift capsules and replace loading tray above the bed. Sealing tray is pressed on top, locking the body and caps making the capsules whole again.

Question 12

Explain the structure of dosator tubes.

Answer 12

A dosator consists of cylinder tube fitted with a moveable piston. The end of the tube is open and the piston is set to a particular height to equate to a volume at the end of the tube for the desired volume of powder.

Question 13

How do dosator devices work?

Answer 13

Encapsulator machine is switched on which forces the dosator into the powder bed.
Powder fills the cavity and the plunger compacts the powder (locking it).
Dosator retracts from the powder bed, containing the powder. Any excess powder at the tip is cut off.
Dosator can now eject the powder into the capsule bodies.

Question 14

How is powder released from the capsules?

Answer 14

Firstly the capsule shell must dissolve. Gelatin is soluble at about 30 degrees so it dissolves easily inside the human body.
Then the powder dissolution occurs. The rate of this is determined by the Noyes Whitney equation:

dm/dt = DA (Cs-C)/h

Question 15

What can slow powder dissolution down?

Answer 15

If powder aggregates form (clumps of particles) the surface area decrease which affects the dissolution rate (it decreases).
This can be avoided by decreasing the compaction force of the powder during filling.

Question 16

Apart from powder, what else can hard capsules be filled with?

Answer 16

Can be filled with:
Pellets
Multi particulate systems (granulation)
Liquid (banding occurs to prevent leakage)

Question 17

When are soft capsules used?

Answer 17

To increase drug oral bioavaliability
It is safe for potent and cytotoxic drugs
To avoid issues with compression
Dose uniformity of low dose drugs

Question 18

What are the disadvantages of soft shell capsules?

Answer 18

Specialist equipment required and therefore increased cost

Question 19

Describe the composition of soft capsules.

Answer 19

40-50% of the shell is gelatin
20-30% is plasticizer
30-40% is water which then decreases to 7% when it is dried

Question 20

What are the different formulations of soft capsules.

Answer 20

A soft capsule consists of the shell and the matrix (what is inside). 
The matrix can be filled with: 
Lipophilic solution 
Hydrophilic solution 
Lipophilic suspension 
Hydrophilic suspension 

And the coating can be modified to have a delayed release or enteric coating

Question 21

Describe the rotatory die process.

Answer 21

Essentially there are two rotating discs adjacent to each other but one is moving clockwise and the other anti-clockwise (two cogs turning together). The discs are connected to two tubes: one containing the gelatin liquid for the shell and the other the liquid drug. At the 12 o’clock position the gelatin is dropped into the dipped capsule hole in each disc. When the filled cogs are about to meet at the 3 and 9 o’clock position the medication is added in and then the capsule is sealed.

Question 22

What are the key differences between soft and hard capsules?

Answer 22

Soft capsules can take a vast number of shapes.

Hard capsules mainly just take solids whereas soft capsules can contain solids, liquids and semisolids.

Hard shells contain: gelatin, colour, titanium dioxide
Soft shells contain: gelatin, colour, plasticizer, water

Hard are less flexible, soft more flexible

Hard capsules are filled and then sealed but soft capsules they are filled and sealed in the same step.

Hand filling is possible with hard capsules but not soft.

Question 23

What are examples of filling materials that are not appropriate inside soft capsules?

Answer 23

Water, hygroscopic and volatile materials, due to their potential to degrade the coating. In contrast, aldehydes are also not appropriate as they can harden the shell which would affect the dissolution properties of the capsule. Acidic and alkaline solutions can’t be in the filling material as the pH may cause hydrolysis of the shell.

Question 24

What sort of materials are able to be filled in capsules?

Answer 24

Water-immiscible (lipophilic)- liquids/oils that are not able to be mixed with water

Water-miscible (hydrophilic) liquids- liquids that can be mixed with water

Self-emulsifying oils- isotropic mixtures of oils, co-solvents, surfactants, co-surfactants and rug molecules

Microemulsion and nanoemulsion systems- isotropic liquid mixtures of oil, water and surfactant, frequently in combination with a cosurfactant

Suspensions- a liquid with solid drug particles ‘suspended’ within it

Question 25

What are four of the key advantages of using soft shell capsules?

Answer 25

Increase rate of absorption
Increased bioavailability
Increase stability
Safe to manufacture for potent and cytotoxic drugs

Question 26

How would you increase the absorption of hormonal drugs?

Answer 26

Dissolve them in an oil solution. This makes the drug molecules lipophilic enabling them to cross the cell membrane, increasing the absorption rate.

Question 27

Describe how use of soft shell capsules increases the rate of absorption for poorly water soluble drugs?

Answer 27

Essentially by coating the capsules with an easily degradable material, the shell can rupture instantly releasing the material inside instead of having to wait for for the tablet to become granules. The drug molecules can be in a hydrophilic/surfactant solution which would again increase the rate of absorption.

Question 28

What happens to acid insoluble drugs in the stomach?

Answer 28

They form precipitate within the stomach, this increases the surface area and therefore the dissolution rate.

Question 29

What are chylomicrons?

Answer 29

They are lipoproteins that transport dietary lipids from the intestine to other locations within the body, some drugs are transported into the circulatory system alongside dietary proteins.

Question 30

Which types of drugs are absorbed via the lymphatic system?

Answer 30

Primarily lipophilic drugs, fat soluble vitamins and water insoluble peptide like molecules.