Poor preservation efficacy versus quality and safety of pediatric extemporaneous liquids.
BACKGROUND
Most medicines are available only as solid, adult-strength dosage forms from which oral extemporaneous liquids are often prepared for children. There are few comprehensive reference lists for the preparation of pediatric extemporaneous formulations. Some pediatric reformulations are made by diluting the suspending vehicle, and a shelf life of up to 3 months can be used without documented microbial stability. Although most commercially available ready-to-use vehicles are supplied as preserved formulations, it is still common practice in many European dispensaries to prepare and dilute these vehicles as required for specific prescriptions.


OBJECTIVE
To determine what influence dilution of vehicles has on the preservation efficiency of extemporaneous formulations.


METHODS
Suspending vehicles were made by diluting methylcellulose 1% and simple syrup, BP (British Pharmacopoeia) in ratios of 1:1 and 1:4. The efficacy of antimicrobial preservation was tested according to the 2007 standards required by the BP.


RESULTS
Dilution in ratios greater than 1:1 failed the BP 2007 criteria. Such dilution represents a potential biohazard, especially to premature, newborn, or immunocompromised children, exposing them not only to possible organoleptic changes of the preparation, but also to ingestion of either dangerous numbers of microorganisms or medicines that may have undergone biotransformation, rendering them inactive or toxic.


CONCLUSIONS
Significant concerns have been raised regarding the quality of extemporaneous preparations. We call for further research in this neglected area to address issues of antimicrobial preservation, including revision of existing quality assurance monographs. Moreover, these monographs should take into account testing that simulates multiple dosing from a single storage container during the intended in-use shelf life of multidose extemporaneous preparations.
Ghulam
Asif
A
The School of Pharmacy, University of London, London, England.
Keen
Kate
K
Tuleu
Catherine
C
Wong
Ian Chi-Kei
IC
Long
Paul F
PF
D000890:Anti-Infective Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D015169:Colony Count, Microbial; D004304:Dosage Forms; D004339:Drug Compounding / Q000592:standards*; D004355:Drug Stability; D005060:Europe; D006801:Humans; D008747:Methylcellulose / Q000737:chemistry; D010226:Parabens / Q000494:pharmacology; D010372:Pediatrics; D004364:Pharmaceutical Preparations / Q000592:standards*; D014677:Pharmaceutical Vehicles; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D013395:Sucrose / Q000737:chemistry
D000890:Anti-Infective Agents; D004304:Dosage Forms; D010226:Parabens; D004364:Pharmaceutical Preparations; D014677:Pharmaceutical Vehicles; D011310:Preservatives, Pharmaceutical; D013395:Sucrose; D008747:Methylcellulose