Preservation of liquid drug preparations for oral administration.
The aim of this study was to investigate functional interactions between sorbic acid, alcoholic cosolvents, and pH with respect to pharmacopeial requirements for the antimicrobial preservation of oral liquids. Twenty-seven test formulations of sugar-free syrups with varying amounts of glycerol (18-36%), propylene glycol (4-21%), and sorbic acid (0-0.15%) and with different pH values (5-8) were tested for antimicrobial preservation efficacy after inoculation with spores of Aspergillus niger. Multivariate data analysis revealed that at pH 5 the minimum concentration of sorbic acid necessary for a tenfold decrease of viable spores ranges between 0.08% and 0.10% exhibiting only minor dependence on the cosolvents concentration. Various interactions between sorbic acid and cosolvents could be observed and were discussed on basis of the degree of dissociation and distribution of sorbic acid. All tested preparations, even those free of sorbic acid, met the criteria for oral products with aqueous bases according to USP32-NF27 and JP XV which claim no increase from the initial spore count at 14 and 28 days. The EP requirement, not less than 1 log(10) reduction from the initial count at 14 days, was only met by preparations with pH 5 and not less than 0.15% sorbic acid.
Scheler
Stefan
S
Department of Pharmaceutical Technology, Friedrich Schiller University of Jena, Jena, Germany. stefan.scheler@sandoz.com
Saupe
Sebastian
S
Herre
Angela
A
Fahr
Alfred
A
D000284:Administration, Oral; D001234:Aspergillus niger / Q000187:drug effects / Q000254:growth & development; D015169:Colony Count, Microbial; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology; D005990:Glycerol / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D015999:Multivariate Analysis; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000737:chemistry / Q000592:standards*; D011310:Preservatives, Pharmaceutical / Q000737:chemistry* / Q000494:pharmacology; D019946:Propylene Glycol / Q000737:chemistry / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry / Q000494:pharmacology; D013011:Sorbic Acid / Q000737:chemistry / Q000494:pharmacology; D013172:Spores, Fungal / Q000187:drug effects / Q000254:growth & development
D005079:Excipients; D019999:Pharmaceutical Solutions; D011310:Preservatives, Pharmaceutical; D012997:Solvents; D019946:Propylene Glycol; D005990:Glycerol; D013011:Sorbic Acid