Formulation of Advanced or Complex Medicines 18 Flashcards
What is the function of flavourings?
Used for taste masking of bitter active
Give examples of colourants that can be used in tablets and capsules
Soluble dyes
Insoluble pigments
What is the difference between a dye and a pigment?
Dyes
- water soluble
- azo
- non-azo
Pigments
- water insoluble
- titanium dioxide
- iron oxides
- yellow
- red
- black
- although all look brown!
- lake form of soluble dyes
- makes it insoluble
What are the proportions of API and excipients in a direct compression tablet?
API
- 1 part
Diluent
- 2 - 3+ parts
- brittle fracture
- plastic
= 95% of tablet
Disintegrant
- super disintegrant
- 2 - 4%
Glidant
- colloidal silicon dioxide
- 0.5% - 1.0%
Lubricant
- magnesium steraate
- 0.5% - 1.0%
How does an effervescent tablet work?
Disintegration by release of gas
- carbon dioxide
- fizzing
What chemicals are in an effervescent tablet to make them fizz?
Reaction between carbonate or bicarbonate and weak acid
- citric acid
- tartaric acid
How is an effervescent tablet made?
Prepared by direct compression or by
- wet fusion
- citric acid is moistened and added to sodium bicarbonate and granulated
- most citric acid acts to partially fuse the powders
- granules are then dried at 70C
- heat fusion
- dry powders are blended with citric acid monohydrate and heated to produce granules
How do chewable tablets work?
Mechanical disintegration in the mouth
No disintegrant in the formulation
Diluents chosen for their sensory properties
- mannitol
- coolant
- negative heat enthalpy
- sobitol
Flavours added to improve taste
How do buccal/sublingual tablets work?
Standard tablets, small size
- formulated for fast disintegration
Designed for absorption in buccal cavity achieve rapid action or to avoid first-pass metabolism
Sublingual
- placed under tongue
- glyceryl trinitrate (GTN)
- buprenorphine
Buccal
- placed in side of cheek
- prochlorperazine (Buccastem)
- NOW WITHDRAWN
How do orally disintegrating tablets (ODT) work?
Disintegrate in mouth in < 10 seconds
- not designed for buccal absorption
- equivalent to standard immediate release tablets
Designed for aiding compliance of patients who have difficulty in swallowing standard tablets and capsules
- elderly
- children
- bed-ridden
Active people who have no access to water for swallowing standard Solid Oral Dosage form
Formulation
- many patented processes
- proprietary information
Give examples of orally disintegrating tablets (ODT)
Standard tablets
Compression moulded tablets
Freeze-dried tablets
Taste masking of API, flavours and sweeteners not sufficient
Coating of powder particles with polymers that do not completely dissolve until stomach
- using effervescence
What is the formulation of orally disintegrating tablets?
Rapidly soluble compounds
- sucrose
- amorphous
- mannitol
- cool feel
- negative heat of solution
- lactose
- amorphous
- partly amorphous
Super disintegrants
- up to 10% w/w
Moderate compression forces
- less air pushed out
- achieve high porosity with adequate hardness and friability
How are freeze-dried tablets made?
Solution made and dispensed into pre-formed blisters
Passed through a cryogenic freezing process that controls ice crystal size, hence tablet porosity
Frozen blisters transferred to large freeze driers
Finally open blisters have lids added and heat sealed
Why is only a sample of drug powder tested for quality assurance?
It is destructive so can’t be used for patients
It would take a long time!
What is the best method for sampling solid raw materials?
Take from a moving stream
Take number of samples, test identity of each one, then combine for assay
