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i- Organic mercury compounds, e.g. phenyl mercury nitrate (toxic)
ii- Phenols and cresols (irritant to mucous membrane)
iii-Benzyl alcohol
iv-Sorbic acid and potassium sorbate (discoloration)
v-Quaternary ammonium compounds (benzalkonium Cl)
vi-High % of alcohol or propylene glycol greater than 30%, no need for preservative

▪ In creams, the problem with preservation arises from the fact that creams are multiphase (contain
water and oil), so microbes attack the water phase

▪ Preservatives are active in their unionized from and they will partition in favor of the oil so, low
sub effective concentration of the preservative will be present in aqueous phase

▪ This could be solved be
i- Use high concentration of preservative (4 times) that used for aqueous solution
ii- Add propylene glycol to increase partition of preservative in water phase

3. Water loss and Humectants:
▪ Creams and gels may lose water either during storage or when applied to the skin leading to
thickening of the product and decrease in its spreadability.
▪ That could be solved by: addition of humectants such as propylene glycol and glycerol
which bond water and minimize water lose during storage and application.

4.Poor permeability and permeation enhancers:
▪ Some topical semisolid preparations are intended to penetrate the skin for subcutaneous or
systemic treatments and for those with poor permeability, penetration enhancers could be
used to improve permeation.
▪ Examples of penetration enhancers include,
i-Propylene glycol (change skin structure)
ii-Dimethyl sulphoxide (DMSO)
iii- Dimethyl isosorbide
iv-Occlusive base (increase skin hydration and porosity and subsequently permeation)

5. Additional/alternative solvents
▪ These are hydrophobic liquid components that may be added to ointment bases
(hydrophobic or absorption bases). Examples of these include:

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