Formulation of Advanced or Complex Medicines 22 Flashcards
Why does viscosity need to be carefully controlled in eye drops?
Increasing viscosity does not necessarily increase drug penetration and can reduce tolerability
- much more irritating
- increased blinking
- reduced drug diffusion
- increased tears
What do weak bases in eye drops form?
Hydrochloride
Sulphate
- gentamicin sulphate
Nitrate
Acetate
- hydrocortisone acetate
Phosphate
Hydrobromide
What do weak acids in eye drops form?
Sodium salts
- diclofenac sodium
- flurbiprofen sodium
How are non-soluble formulated for eye medication?
Oily or aqueous suspensions
What are the particle sizes in eye suspensions?
Solid particles must be very finely divided (micronised) and comply with Particle Size Test
- not more than 20 particles > 25 um
- not more than 2 of these > 50 um
- none > 90 um
in an area corresponding to 10 ug solid phase
Give examples of wetting agents used in eye suspensions
Non-ionic surfactants are less toxic than cationic or anionic surfactant
- polysorbate 80
What are the problems with the stability of eye drops?
Oxidation
pH/buffering
Tonicity
Give examples of antioxidants that are used in eye drops
Sodium metabisulphite
Sodium sulphite
Ascorbic acid
Acetylcysteine
Why is controlling tonicity in eye drops important?
Ophthalmic solutions should be isotonic with lachrymal secretions
- ideally equivalent to 0.9% NaCl
Acceptable range 0.7 - 1.5%
How can hypotonic solutions be adjusted for tonicity?
NaCl
KCl
glucose
glycerol
buffers
Why are preservatives needed in eye drops?
- Poor blood supply inside eyeball capillaries in eye are not very accessible
- Isn’t aseptic preparation sufficient? most eye preparations come as multidose containers
- Eye preparations for multi-use should contain a suitable antimicrobial preservative (NB not if used in surgery – single use) pt could touch container with eye or finger (contamination)
- preservative needs to be suitable for product
- Remember - the Cornea is sensitive to chemicals (toxic conjunctivitis)
Why is benzalkonium chloride used in eye drops as a preservative?
Well tolerated in the eye at concentrations up to 0.02%
- normally used at 0.01%
Non-volatile
Stable to autoclaving
Bactericidal against a wide range of Gram positive and Gram negative bacteria
What is the problem with using benzalkonium chloride as a preservative in eye drops?
Some people can be hypersensitive
Why is chlorhexidine used in eye drops as a preservative?
Effective at 0.01% against most bacteria
- especially Gram positive
How is the activity of chlorhexidine preservatives in eye drops be reduced?
Metal ions and anionics and incompatible with sulphates
