Manufacture and Testing of Capsules (M3)

Question 1

What are hard capsule shells made from?

Answer 1

Gelatin

Question 2

Why is gelatin a great material to make hard capsule shells from?

Answer 2

• Non toxic
• Readily soluble in biological fluids
• Good film forming material

Question 3

What is bloom strength?

Answer 3

Bloom Strength is a measure of gel strength/rigidity

• Comes from the bloom strength test, where a plunger is pushed 4mm into a gel and the force required in grams is the strength value

Question 4

What does viscosity determine in hard capsule fabrication

Answer 4

• Molds are dipped into the gelatin solution
• The more viscous the solution the thicker the film that is left on the mold

Question 5

What types of gelatin are hard gelatin capsules made from and what properties does each type offer?

Answer 5

Bone gelatin (Type B) for toughness
Pork skin gelatin (Type A) for plasticity

Question 6

What are the plasticisers often added to melted gelatin and how do they help?

Answer 6

• Glycerol or propylene glycol
• They ensure the gelatin remains flexible during its lifetime and does not get brittle

Question 7

Preservatives are also added to HGC, what do these do?

Answer 7

• HGCs have a 13% water content
• preservatives prevent bacterial growth and contamination

Question 8

What are all the ingredients to make a HGC shell

Answer 8

• Gelatin (Type A and B)
• Plasticisers (Glycerol or propylene glycol)
• Preservatives
• Colours (dyes)
• water

Question 9

How are capsule shells made?

Answer 9

• Gelatin solution is made
• Mold dips into the solution
• The dip coated molds are left to settle and dried
• the shells are stripped from the molds
• The shells are trimmed/cut to size
• capsule shells filled and joined

Question 10

What are Capsules filled with?

Answer 10

• A granule/powder consisting of:
  API
  Diluent
  Wetting agent
  Glidant
  Lubricant

Question 11

Does it matter is the diluent is soluble or not in hard capsules?

Answer 11

The diluent should have opposite soluble properties to avoid competition for bodily solute

eg, an insoluble API needs a soluble diluent, and a soluble API needs an insoluble diluent

Question 12

What is the purpose of a glidant and give an example of one

Answer 12

to improve flow properties
- talc or silicon dioxide

Question 13

Why is a lubricant needed in the powder formula for HGCs?

Answer 13

• To reduce particle metal friction and sticking during the filling process
• Allows more accurate dosing and no failures in the machinery

Question 14

Why is a wetting agent used in the powder formula for the excipient in APIs?

Answer 14

Wetting agents are substances that improve the wetting and dispersion of powders, making them easier to mix with liquids and disperse uniformly

Question 15

HGCs can also be filled with pellets, what are the advantages to these?

Answer 15

• Exceptionally free flowing
• no exhibited cohesion
• Different filling mechanism is used (less clogging)

Question 16

Filling capsules employs the double slide mechanism, how does this work?

Answer 16

1) The pellets are released from a hopper into a dosing chamber
2) The chamber is closed off from the hopper once filled
3) The outlet slide opens releasing the controlled dose into the capsule

Question 17

Hard gelatin capsules can be filled with thermosoftening mixtures, how is this done?

Answer 17

• The API is dispersed in a hot melted polymer which is pumped into the capsule and then solidifies upon cooling

Question 18

Hard gelatin capsules can also be filled with thixotropic semi-solids, how does this work?

Answer 18

• Under pressure thixotropic materials become liquid like (opposite to ooblek)
• The API dispersed in a thixotropic base is pumped into the capsule
• once the base isn’t being sheared it becomes solid

Question 19

Capsules can also be filled with tablets? why might this be useful?

Answer 19

• To achieve more optimal release characteristics (slower or delayed release)

Question 20

What are the different options for filling a HGC?

Answer 20

Question 21

There are 4 different types of filling mechanisms, but they all have the same Principle steps, what are they?

Answer 21

1) Position the capsule correctly
2) Separate the 2 halves
3) Fill the lower half with formulation
4) Replace the cap allowing air to escape during the refit
5) Lock the halves together

Question 22

What are the 4 different techniques used to actually fill the capsule?

Answer 22

1) Flooding
2) Plugging
3) Vacuum
4) Tamping

Question 23

What is flooding (technique used to fill HGCs)?

Answer 23

• Add a series of open capsules onto a grooved capsule filler (special tray)
• Once in position, flood the tray with powder
• Distribute the powder among the capsule bases
• Join the capsules together

Question 24

What is plugging (technique used to fill HGCs)?

Answer 24

• Most commonly used system
• A dosage tube containing a spring loaded plunger
  1) The dosage tube is submerged into the powder.
  2) The spring retracts pulling up the plunger syringing up a dose of powder
  3) The dose is released into a capsule

Question 25

What powder properties does plugging rely on?

Answer 25

- Cohesiveness - Powders than flow well will be lost

Question 26

How does vacuum capsule shell filling work?

Answer 26

- Similar to Plugging - Negative pressure is used to extract the powder but instead compressed air is used to expel the powder - This can be done on any powder, doesn't have to be cohesive

Question 27

Describe the capsule filling method tamping and when it is used

Answer 27

- Used for powders with poor flow rates - The hopper uses a tamping or auger device, which is like a screw with longer threads, to force out the powder

Question 28

Post filling, capsules need to be sealed, what 3 methods are there to do this?

Answer 28

- Spot welding - Banding - Locking

Question 29

Describe how capsules are sealed via locking

Answer 29

- The principle of locking is that there is a ring of indentation on the shell and cap that lock together

Question 30

What are the sealing methods banding and spot welding in terms of drug capsules?

Answer 30

Banding - A band/strip of molten gelatin is formed around the join site of the 2 halves Spot welding - A hot probe is used to weld the 2 halves together where they overlap

Question 31

Describe the size chart for capsules

Answer 31

- 8 sizes available from 5 - 000 5 is the smallest, while 000 is the largest

Question 32

What is the equation that links a capsule fill weight to vol and tapped density?

Answer 32

Question 33

What are a few advantages of hard and soft capsules over tablets? (4)

Answer 33

1) Good for masking taste and odour 2) They can look attractive (colours can elicit psychological effects) 3) Easy to administer (capsules become slippy and easy to swallow when wet) 4) Mechanically strong but flexible (not friable) 5) Fewer ingredients than tablets (less stability and manufacture problems) 6) Good bioavailability

Question 34

What are a few disadvantages of hard and soft gelatin capsules in comparison to tablets? (3)

Answer 34

1) Rate of capsule filling and sealing is much slower than tablets (165,000 to 600,000 per hour) 2) Can often have poor weight uniformity and by extension poor content uniformity 3) High cost of initial equipment

Question 35

Similar to tablets, capsules are product tested, list a few of these tests

Answer 35

- Content of API in capsule - Uniformity of mass - Disintegration test - Dissolution rate test - Sometimes appearance testing

Question 36

How must capsules be packaged?

Answer 36

- In containers impervious to moisture - Away from direct sunlight - relatively low humidity areas (<60%) - in less than 25 degrees C

Question 37

What are the 2 methods used to produce soft gelatin capsules?

Answer 37

- Globex method - Rotary Die Method

Question 38

Describe the Globex method

Answer 38

1) Hot Gelatin solution is maintained in a tank at 80 degrees C, while the excipient is in another tank 2) A dose of both solutions are pumped out of their tanks simultaneously through a double dosing tube 3) Because of the double dosing tube, the gelatin encapsulates the excipient, forming s spherical shape to reduce the interfacial free energy 4) The soft gelatin capsule falls through a cooling liquid and is collected, washed and dried at the end

Question 39

Describe the Rotary Die method

Answer 39

- two molten ribbons of gelatin are fed over 2 die rolls - As the ribbons are pressed together, the excipient is dispersed into the gap between them - The 2 ribbons are sealed together by the rotating die, enclosing the formulation - The soft gel capsules are then cut from the gelatin ribbon and allowed to cool and dried (Note this method has a lot of waste gelatin)

Question 40

In soft gel capsules how is the API usually disperesed?

Answer 40

Usually in an oily base