Manufacture and Testing of Capsules (M3) Flashcards
Mark Lecture 3 of 4
What are hard capsule shells made from?
Gelatin
Why is gelatin a great material to make hard capsule shells from?
- Non toxic
- Readily soluble in biological fluids
- Good film forming material
What is bloom strength?
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
What does viscosity determine in hard capsule fabrication
- Molds are dipped into the gelatin solution
- The more viscous the solution the thicker the film that is left on the mold
What types of gelatin are hard gelatin capsules made from and what properties does each type offer?
Bone gelatin (Type B) for toughness
Pork skin gelatin (Type A) for plasticity
What are the plasticisers often added to melted gelatin and how do they help?
- Glycerol or propylene glycol
- They ensure the gelatin remains flexible during its lifetime and does not get brittle
Preservatives are also added to HGC, what do these do?
- HGCs have a 13% water content
- preservatives prevent bacterial growth and contamination
What are all the ingredients to make a HGC shell
- Gelatin (Type A and B)
- Plasticisers (Glycerol or propylene glycol)
- Preservatives
- Colours (dyes)
- water
How are capsule shells made?
- 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
What are Capsules filled with?
- A granule/powder consisting of:
API
Diluent
Wetting agent
Glidant
Lubricant
Does it matter is the diluent is soluble or not in hard capsules?
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
What is the purpose of a glidant and give an example of one
to improve flow properties
- talc or silicon dioxide
Why is a lubricant needed in the powder formula for HGCs?
- To reduce particle metal friction and sticking during the filling process
- Allows more accurate dosing and no failures in the machinery
Why is a wetting agent used in the powder formula for the excipient in APIs?
Wetting agents are substances that improve the wetting and dispersion of powders, making them easier to mix with liquids and disperse uniformly
HGCs can also be filled with pellets, what are the advantages to these?
- Exceptionally free flowing
- no exhibited cohesion
- Different filling mechanism is used (less clogging)
Filling capsules employs the double slide mechanism, how does this work?
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
Hard gelatin capsules can be filled with thermosoftening mixtures, how is this done?
- The API is dispersed in a hot melted polymer which is pumped into the capsule and then solidifies upon cooling
Hard gelatin capsules can also be filled with thixotropic semi-solids, how does this work?
- 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
Capsules can also be filled with tablets? why might this be useful?
- To achieve more optimal release characteristics (slower or delayed release)
What are the different options for filling a HGC?
There are 4 different types of filling mechanisms, but they all have the same Principle steps, what are they?
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
What are the 4 different techniques used to actually fill the capsule?
1) Flooding
2) Plugging
3) Vacuum
4) Tamping
What is flooding (technique used to fill HGCs)?
- 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
What is plugging (technique used to fill HGCs)?
- 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
What powder properties does plugging rely on?
- Cohesiveness
- Powders than flow well will be lost
How does vacuum capsule shell filling work?
- 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
Describe the capsule filling method tamping and when it is used
- 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
Post filling, capsules need to be sealed, what 3 methods are there to do this?
- Spot welding
- Banding
- Locking
Describe how capsules are sealed via locking
- The principle of locking is that there is a ring of indentation on the shell and cap that lock together
What are the sealing methods banding and spot welding in terms of drug capsules?
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
Describe the size chart for capsules
- 8 sizes available from 5 - 000
5 is the smallest, while 000 is the largest
What is the equation that links a capsule fill weight to vol and tapped density?
What are a few advantages of hard and soft capsules over tablets? (4)
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
What are a few disadvantages of hard and soft gelatin capsules in comparison to tablets? (3)
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
Similar to tablets, capsules are product tested, list a few of these tests
- Content of API in capsule
- Uniformity of mass
- Disintegration test
- Dissolution rate test
- Sometimes appearance testing
How must capsules be packaged?
- In containers impervious to moisture
- Away from direct sunlight
- relatively low humidity areas (<60%)
- in less than 25 degrees C
What are the 2 methods used to produce soft gelatin capsules?
- Globex method
- Rotary Die Method
Describe the Globex method
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
Describe the Rotary Die method
- 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)
In soft gel capsules how is the API usually disperesed?
Usually in an oily base
