Preservation Flashcards
What is the potential fate of preservative molecules in pharmaceutical products?
Much depends on the state ionisation of the molecules.
- Partitioning into oil droplets or surfactant micelles can occur, as well as adsorption onto suspend solids
- Adsorption, sorption or permeation of plastic closures can occur, leaving less active form in the aqueous phase
What is the fate of preservative in suspension?
What is the potential fate of preservative in emulsion?
What reduces preservative efficacy? Provide some examples.
Adsorption onto the surfaces of suspended drug and cosmetic ingredients can also significantly reduce preservative efficacy
- Parabens onto magnesium trisilicate
- Chlorhexidine onto mineral earths such as kaolin and calamine
- Parabens onto cosmetic pigments
- Benzoic acid onto sulphadimidine particles
What is a particular problem with adsorption in preservatives and plastic containers?
In some cases, adsorption is followed by absorption into the solids– a particular problem with preservatives and plastic container
- Phenolics and parabens absorb appreciably into nylon and plasticised PVC
- Chlorobutanol is absorbed appreciably into polyethylene bottles during autoclaving
Preservatives first adsorb to walls of the container and then preservatives absorbs into container walls and may evaporate
Discuss the use of preservation in suspensions.
- Naturally occurring additives such as acacia and tragacanth may be sources of microbes and spores.
- Preservative action may be diminished because of adsorption of the preservative onto solid particles of drug, or interaction with suspending agents.
Useful preservatives in extemporaneous preparation include chloroform water, benzoic acid, and hydroxybenzoate
What are some magnesium mixtures?
Magnesium trisilicate mixture BP has sodium methyl hydroxybenzoate and sodium propyl hydroxybenzoate
What preservative does cefalexin sandoz have
Powder for oral suspension (orange/ yellow colour, fruity flavour), 125 mg/5 mL, 250 mg/5 mL
Suspension:. Saccharin sodium, iron oxide yellow CI77492, simethicone, anhydrous citric acid, strawberry, apple, raspberry and tutti frutti artificial flavouring, guar gum, sodium benzoate and sucrose
Poweder for oral suspensions: Before mixing: store below 25 deg. C. Protect from light and moisture. After mixing: store at 2 to 8 deg. C. (Refrigerate. Do not freeze) and discard unused portion 14 days after reconstitution.
What preservative does Mylanta heartburn relief have?
Each 20 mL contains:
- aluminium hydroxide-dried (equiv. aluminium oxide 50%) 400 mg,
- magnesium hydroxide 400 mg,
- calcium carbonate 500 mg,
- sodium bicarbonate 500 mg,
- alginic acid 310 mg;
- sodium 6.4 mmol,
- butyl hydroxybenzoate,
- propyl hydroxybenzoate
- saccharin sodium.
What do preservative molecules do in a multiphase formulation (eg o/w emulsion)
Preservative molecules will distribute themselves in an unstable equilibrium between the bulk aqueous phase and
- The oil phase by partition
- The surfactant micelles by solubilization
- Container surfaces by adsorption
- Microorganisms present
What is the distribution coefficient?
C1/C2 = K
C1 and C2 are the equilibrium concentrations of the substance in solvent 1 and solvent 2, respectively.
K = equilibrium constant.
> Solvent 1 and solvent 2 are immiscible, solute does not undergo molecular association in organic phase or ionic dissociation in aqueous phase
What is the formula for partitioning between oil and water? What effect does partition coefficient have in preservative levels?
Cw = C (ϕ +1) / (Kow * ϕ + 1)
C = total preservative concentration
Cw = concentration of preservative in aqueous phase
ϕ= oil/water ratio
Kow = partition coefficient
- If Kow is high, then it becomes extremely difficult to maintain adequate preservative levels in the aqueous phase without an excessive total preservative concentration.
- If Kow = 1 (C is fixed), changes in ϕ (oil water rate ) does not influence preservative concentration
- If Kow > 1 (C is fixed), increase in ϕ, will cause decreased Cw (concentration of preservative in aqueous phase)
- If Kow < 1 (C is fixed), increase in ϕ, will cause increased Cw (concentration of preservative in aqueous phase)
See attached example
Why are o/w emulsions more susceptible to spoilage?
- o/w emulsions are particularly susceptible to spoilage as the water in the continuous phase allows contaminants to spread throughout the product.
> Preservatives generally exert their influence only within this phase and at its boundaries.
- Concentration depends on their relative solubilities in the particular oil and in water, and on the oil water ratio in the emulsion.
What does the addition of an emulgent do?
The inclusion of an emulgent in the system results in a redistribution of the preservative between the total aqueous phase and the oil.
- Emulgent (nonionic) is a third component and is considered to be present in aqueous phase (A)
What is the relationship between preservatives and non-ionic surfactant?
Possess no intrinsic activity, generally a diminution of antimicrobial activity
- Interaction of preservatives with non-ionic surfactants could be the result of either micellar solubilization or complex formation between the two molecules
- The amount of preservative bound to a nonionic surfactant is directly related to the surfactant concentration: R = SC + 1
R: ratio of total to free (unbound) preservative concentration;
C: surfactant concentration
S: a constant, which has a unique value for each surfactant-preservative mixture, which increases in value as the lipid solubility of the preservative increases
What is the formula for oil/water surfactant?
