Source of Bacteriostatic water

{{Infobox concept | name = Bacteriostatic water | subtitle = Diluent | Composition = Water for injection with 0.9% benzyl alcohol | Function of the preservative = Inhibits microbial growth after entry | Contrast with = [[Sterile water for injection]], unpreserved }} '''Bacteriostatic water''' is sterile water containing an antimicrobial preservative, conventionally benzyl alcohol at 0.9%. The preservative does not sterilise; it inhibits the growth of organisms introduced when a container is entered, which is what makes multiple withdrawals from one container possible. See [[Multi-dose vial]].{{r|usp51}} It is a diluent, not a treatment for non-sterile material. Adding it to a powder that was never sterile produces a non-sterile solution containing a preservative — the preservative retards growth of what is there rather than eliminating it.{{r|usp797}} Benzyl alcohol is not inert. It has recognised toxicity at high cumulative exposure, is contraindicated in neonates, and can interact with certain formulations. Where a peptide is known to be preservative-sensitive, an unpreserved diluent is used and the container treated as single-entry.{{r|usp1503}} == What the preservative does == Antimicrobial effectiveness is a defined pharmacopoeial property: a preserved preparation is challenged with specified organisms and must reduce their numbers by defined amounts over defined intervals. Benzyl alcohol meets that requirement over the concentration and pH ranges in which it is used.{{r|usp51}} Inhibition is not immediate and not universal. Some organisms are more resistant than the challenge panel, and preservative efficacy falls with dilution — a preserved diluent added to a large volume of unpreserved liquid may fall below its effective concentration. The preservative also does nothing about chemical degradation. A preserved solution remains subject to [[Deamidation|deamidation]], oxidation and [[Peptide aggregation|aggregation]], and the presence of a preservative does not extend chemical stability at all.{{r|manning2010}} == Interaction with peptides == Benzyl alcohol is a small amphiphile and can promote aggregation in some proteins and peptides, an effect documented in the biopharmaceutical literature for several molecules. Whether a given peptide is affected is molecule-specific and is established experimentally.{{r|manning2010}} This is the reason preserved and unpreserved presentations of the same active substance exist. Where a molecule is preservative-sensitive, single-entry containers with unpreserved diluent are used, and the container is discarded after one withdrawal rather than dated for repeated entry. For research peptides no such compatibility data generally exist. The absence of data is not evidence of incompatibility, and the honest position is that the interaction is uncharacterised for most of the compounds this wiki covers.{{r|usp1503}} == Common misunderstandings == Three claims circulate widely and none is correct. * That bacteriostatic water sterilises a preparation. It does not; it inhibits growth. A non-sterile powder gives a non-sterile solution. * That the presence of a preservative extends the chemical stability of a peptide. It does not; the two are unrelated mechanisms. * That "bacteriostatic" and "sterile" are interchangeable descriptions of the same product. They are different products with different indications. The distinction that matters practically is between single-entry and multiple-entry use, which is what the preservative addresses. See [[Multi-dose vial]] and [[Beyond-use date]].{{r|usp797}} Nothing on this wiki is medical advice, and research-use compounds are not approved for human administration. == References == {{reflist}} <ref name="usp51">United States Pharmacopeia, General Chapter <51>, ''Antimicrobial Effectiveness Testing''.</ref> <ref name="usp797">United States Pharmacopeia, General Chapter <797>, ''Pharmaceutical Compounding — Sterile Preparations''.</ref> <ref name="manning2010">Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. "Stability of protein pharmaceuticals: an update." ''Pharmaceutical Research'' 27(4):544–575 (2010). PMID 20143256.</ref> <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> == See also == * [[Sterile water for injection]] * [[Reconstitution of lyophilised peptides]] * [[Multi-dose vial]] * [[Beyond-use date]] * [[Sterility testing]] {{DEFAULTSORT:Bacteriostatic water}} [[Category:Preparation and handling]] [[Category:Clinical practice]] [[Category:Compendial testing]]