NOVEL APPROACH TO THE ASSESSMENT OF PRESERVATION EFFECT FOR ORAL LIQUID PHARMACEUTICAL PRODUCTS

Abstract

Preservation of multidose pharmaceutical products is essential criterion for both the efficacy and the safety of medicinal products for human consumption. Yet, there are still several reports of contamination of several products either for treatment of hospitalized or outpatients. This current study aims to provide new approach for assessing the preservation of medicinal product using dose-response model of infection. This will involve the most infective bacteria for the route of administration and the application of repeated recontamination of the product using simulation study as a method for risk evaluation. Three different non-sterile oral liquid formulae were subjected to this study. All products passed the preservative efficacy test (PET) with the iron supplement syrup showing the highest rate of microbial count reduction followed by antitussive syrup then antidiarrheal suspension – especially after 14 days of the test - when using Escherichia coli as an indicator microorganism. The application of simulated multi-spot contamination model integrated with both PET and dose-response model of infection showed the reverse order of descending risk of microbial infection. The relative probabilities values of the geometric means for both types of the infection models were approximately 1 : 1.2 : 1.4 for iron supplement : antitussive : antidiarrheal products, respectively. However, these products means did not differ significantly from each other using One-way ANOVA at 95 % confidence interval. On the other hand, the exponential model of enterohemorrhagic (EHEC) E. coli showed from 20 to 34 times higher risk of infection than Beta-Poisson model depending on the level of contamination of the liquid product during in-use application. The study offered new approach of assessing the risk of infection from consumption of contaminated multidose product from in-use application quantitatively.