Formulation of Advanced or Complex Medicines 14 Flashcards
What is the shell of a soft capsule made from?
Gelatine (hydrolysed collagen) or polymer
Colourants
Water
Plasticisers
What is the shell of a hard capsule made from?
Gelatine or polymer
- hypromellose
- vegan
- religious groups
Colourants
Water
How are hard gelatine capsules made?
Mould pin used to determine shape of capsule shell
Gelatine solution in water
- bubble free
- coloured
- viscosity adjusted
- 50 - 55%
- overflowing weir ensures liquid is at constant height for mould pin to enter
Mould pin turns end over end to spread film evenly over pin
Gelatine film set
Drying using large volumes of controlled humidity air and minimum heat
- rate limiting step
Pins cool back to room temperature
- film dried to ~ 16% moisture content
- naturally in gelatin
After removal from the pin, the film at the edge of the shell is think so is cut off to produce a shell of correct length
Capsule shell ‘body’ combined with larger diameter ‘cap’ produced on separate production machinery
- often different colours to broaden range of coloured products available
Capsule shells packaged and shipped to manufacturers where they will be separated, filled and re-sealed before packagaing
What other materials can hard capsules be made from?
Hypromellose
AKA hydroxypropylmethylcellulose
AKA HPMC
What is the problem with using hypromellose for hard capsules?
Does not gel like gelatine
How can the problems of using hypromellose for hard capsules?
Use standard gelatine manufacturing machine
- convert solution to a gelling one by adding a network former and a network promoter
- carrageenan and potassium chloride
- gellan gum and citric acid
Use a non-standard machine
- reverse the process and dip hot mould pins into a solution at room temperature
- 60 - 70C
- the viscosity of HPMC solutions increase as the temperature rises and is sufficient to hold the wet film on the mould until it has been dried
- HMPC sets when hot!
How can capsules be identified?
Colour
- use combinations of approved soluble dyes and insoluble pigments
Printing
- use approved pigments dispersed in organic solutions of shellac
- an edible polymer
Information
- company names and logos
- identity code
- product name
- amount of API
What is the difference between dyes and pigments?
Dyes react chemically to colour a substance
Pigments are naturally that colour
What are the disadvantages of bigger capsules?
More packaging
Higher shipping costs
What can be filled in gelatine capsules?
Many different types provided they can be dosed
- powders
- granules
- pellets
- semi-solids
- liquids
- non-aqueous solutions and suspensions
- water will dissolve capsule shell
What cannot be filled in gelatine capsules?
Gelatine reactors
- formaldehyde
- cross linking -> Reduced solubility
- free moisture
- shells will swell and distort
Large doses
- high bulk volume
- pre-tapped volume
What are the advantages of using hypromellose capsules?
Do not react with formaldehyde
No known cross-linking reactions occurs
What are the important factors to filling and product performance of capsules?
Powder flow
Good flow
- bed reforms homogenously
Bad flow
- bed does not reform homogenously
What is the difference between capsules and tablets?
Capsules
- compression force 10 - 100N
- applied from one end
- high length to diameter ratio
- porous soft compact
- 40 - 50% air
Tablets
- compression force 10 - 100kN
- applied from two ends
- lower length to diameter ratio
- less porous hard compact
- 8 - 12% air
How are most soft shell capsules made?
Rotary die process
