Formulation of Advanced or Complex Medicines 15 Flashcards
What vehicles are used to fill a soft capsule?
Water immiscible non-volatile liquids
- vegetable oils
- synthetic oils
Water-miscible non-volatile liquids
- low molecular weight
- macrogols
- PEG 400
- PEG 600
- non-ionic surfactants
- polysorbate 80
Why are non-volatile liquids used in soft capsules?
Don’t evaporate which increase pressure in capsule, or dry out
Give examples of formulation that can be used in soft capsules
Lipophilic liquids/oils
Hydrophilic liquids
- PEG 400
Self-emulsifying oils
- pharmaceutical oil plus non-ionic surfactant, polyoxyethylene sorbitan mono-oleate
Micro-emulsion and nano-emulsion systems
- fill is lipid plus surfactant(s) forms emulsion spontaneously when shell disintergrates
Suspensions
Which oral formulations are easier to swallow?
Capsules
- longer one way than the other
How can tablets be made easier to swallow?
Caplets
Why do some people struggle to swallow tablets?
Central control
- some can
- some cannot
The way people eat food
- gulpers
- chewers
- soft palette not accustomed to lumps so gag reflex
How can it be made easier to swallow tablets?
Gravity
- sit up
- stand up
Lubricants
- water
Why is it hard to swallow capsules?
Capsule floats on water and touches roof of mouth
- gag reflex
Chewers sensitive to size of object in mouth are unable to swallow
How can it be made easier to swallow capsules?
Lean forward
- capsule floats on water to back of cavity
- does not touch roof of mouth
- no signals to brain
- lift head
- bolus of capsule and water swallowed easily
How is capsule disintegration measured in vitro?
Beaker with stirrer at 60 rpm
Water at 37C
What is the rate controlling step of capsule disintegration?
Formulation of contents
What factors influence tablet or capsule formulation?
API properties
- compactibility
- fluidity
- solubility
- stability
Size of dose of API
How does the API dose influence the formulation?
Low dose (< 25mg)
- most of formulation will be the excipient
CHALLENGE - content uniformity
- big % change if you lose a few API particles
High dose (>250mg)
- most of formulation will be the API
CHALLENGE - compactibility and fluidity
API solubility important for both
- governs selection of excipient
What are the types of excipients used in tablets and capsules?
Diluent/filler
- same thing
Binder
Disintegrant
Lubricant
Glidant
Wetting agent
Stabilisers, colourants and flavours
How can a poorly soluble API be overcome to improve bioavailability?
Use a different salt of the API
- phosphate
Micronise the API powder
- increase SA
- increase rate of dissolution
Use amorphous API
- more unstable
