Jan exam Flashcards
pass January exam
Classifications of common preservatives and characteristics
Acids and esters - active against bacteria and fungi
Alcohols - broad spectrum; poor penetration of organic matter, volatile
Biguanides - active against Gram + bacteria; inactivated by organic matter; limited antifungal activity
Heavy metals (mercury)- Broad spectrum of antibacterial activity; low capacity to organic matter; toxicity issues
Phenol - cheap; activity against fungi and Gram + bacteria; low water solubility; adsorbed by rubber; volatile; irritant; pH dependent
Quaternary ammonium compounds (QACs) - Actviity agianst Gram + bacteria; organic matter affects activity; pH dependent; non toxic
Common preservatives in oral products
alkyl - Parabens
Acids
QAC
Common preservatives in parenteral products
Alcohols Parabens Phenol Heavy metal Biguanides
Common preservatives in topical products
QACs paraben Alcohols Acids Phenols
Common preservatives in Ophthalmic
QACs Heavy metals Acids Biguanides diazolidinyl urea (imidurea)
The use of which preservatives is discouraged and why
Phenols and organo mercurial use in topical and oral products has been discouraged but they are still used to preserve parenteral
Use of older preservatives been largely discontinued largely due to safety issues
MOA for preservative that target cell wall
Lysis due to enzyme inhibition (e.g. phenol and organo mercurial)
Irreversible cross-linking at the cell wall (e.g. glutaraldehye)
MOA of preservatives that target cell membrane
changes to membrane potential, enzymatic function and permeability
Cetrimide, chlorhexidrine, 2-phenoxyethanol, parabens and phenols affect membrane permeability (leading to leaking of cell constituents and cell death)
Sorbic acid inhibits transport mechanisms across the membrane
Chlorhexidrine inhibits membrane ATPase (at higher concentrations causes precipitation of cytoplasmic nucleic acid ad related proteins)
Chelators com-promise membrane integrity by chelating Ca2+ and Mg2+ (this potentiates other anti-microbial agents)
QACs bind strongly to the cytoplasmic membrane (particularly phospholipid bilayer) and cause damage and leaking
MOA of preservatives cytoplasm
Uncoupling of oxidative and phosphorylation processes or interference with active transport mechanisms
Other preservatives inhibit electron transport chains
Benzoic acid and parabens inhibit folic acid synthesis
Bronopol and organomercurials target thiol enzymes
Imidurea act on he carboxylic acid amino enzymes
Phenols and alcohols cause protein denaturation
Preservatives must …?
Exert a wide spectrum of antimicrobial activity at low concentration
remain essentially in aqueous phase multiphase products
Maintain activity throughout product manufacture, shelf life and usage
Not compromise the quality or performance of the product, pack or deliver system
not adversely affect patient safety or tolerance of the product
How does concentration affect preservative efficacy
The higher the concentration of the biocide the greater the rate of killing
What is the concentration exponent (or dilution coefficient)
Is a measure of changes in the preservative concentration on cell death rate
Calculated by comparing the time taken to achieve a similar rate level of killing and different concentrations of biocide
given by the formula
(C1/C2)^n = T2/T1
n = concentration exponent
Preventatives combination
Benzalkomin chloride is inefefctvie agianst some strains of psudomonas aeruginosa (combinations with EDTA, alcohols can enhance anti-Pseudomonas activity)
Parabens activity increase with increase of alkyl chain (but solubility decrease) as a result parabens are usually used in combination (short chain plus and long chain e.g. methyl and propyl-paraben)
Parabens show some synergy with EDTA, 2-phenylethanol and imidurea
Safety and side effects of preservatives
Alcohols are generally considered to be safe (benzyl alcohol can cause fatal toxic syndrome in low weight neonates)
Carboxylic acids can be gastric irritants and, mildly irritant to skin, eye and mucous membranes
Parabens are considered unsuitinble for parenteral and opthalmic use due to irritancy
Use of organo mercurial preservatives is restricted to due to concerns of toxicity. (still widely used in topical and parenteral formulations)
What does a high or low concentration exponent tell you about a preservatives killing time
The killing time of preservatives with low concentration exponents are less affected by changes in concentration
The killing time of preservatives with high concentration exponents values are greatly effected by changes in concentration
