Procedure for rapid determination of bile-tolerant gram-negative bacteria in drugs

Abstract

The European Pharmacopoeia is a single reference study for the quality control of drugs. The official standards published within it provide a legal and scientific basis for quality control in the processes of drugs development, production and marketing. However, the long experience and the multitude of studies have demonstrated that medicinal forms represent unstable dispersed systems and can undergo various manifest or non-manifest changes, leading to drug incompatibilities. Along with the physico-chemical transformations, microbiological transformations can occur with the contamination of the final product with pathogenic, conditionally pathogenic or even saprophytic germs, especially medicines that do not undergo final sterilization or are not aseptically prepared. Microbial contamination of the drug can be an indicator of the production conditions; it can cause the instability of the product through the microbial decomposition of auxiliary substances, the alteration or definitive cancellation of the therapeutic effect of the active substances, the appearance of metabolites with toxic properties, especially those fractions of endotoxins on the wall cell of gram-negative bacteria with the development of allergenic, pyrogenic substances and the induction of the danger of local orgeneral infections. An important role is attributed to the group of bile-tolerant gram-negative bacteria as representatives of microorganisms that are inadmissible in one g/ml for the absence test and for the quantitative test <10 NCP/g/ml (probable number of bacteria), inadmissible in non-sterile medicinal products, herbal medicinal products for oral use and extracts used in their preparation. Due to the diversity of medicinal forms in terms of content, method of application, and therapeutic action, these preparations fulfil the indispensable conditions for the growth of microorganisms, therefore a primary concern is to avoid microbial contamination from the technological phase to the administration phase in order to prevent complications associated with bacterial infections. The given study reveals the testing of the procedure for the rapid determination of inadmissible microorganisms in non-sterile medicinal products and herbal drugs for oral use and the extracts used in their preparation, especially microorganisms of the group Enterobacteriaceae spp.