[Microbiological control of drugs with antimicrobial properties with membrane filtration: problems, proposals, prospects].
The attention to the difficulty to performing the control of sterility (and also of contamination) of pharmaceuticals with antimicrobial activity (antibiotics, chemotherapeutic agents, etc.) or containing preservatives is called. On the basis of our and others investigations, the technique of the membrane filtration (employed usually) is unable to eliminate the interferences on the microbial growth. The membranes used for the filtration of antimicrobial agents acquire antimicrobial properties, resulting in: a) appearance of inhibition zones onto agar plates previously inoculated with microbial strains; b) decrease of the number of CFU after artificial contamination of the membranes (more sensitive method); c) absence or partial growth into culture broths of microbial strains contaminant the membranes; d) antimicrobial activity of the culture broths inoculated with used membranes. The separate washing with 300 ml and upper volumes of peptone water does not eliminate completely the antimicrobial activity of the membranes. If the filtration is associated to treatments with suitable neutralisant substances, it is possible to eliminate partially the antimicrobial activity of the membranes. In No. 10 antibiotics, a total neutralization of the antimicrobial activity was obtained in No. 4 cases (40%). In No. 14 chemotherapeutic agents, We have obtained a total neutralization of the antimicrobial activity in No. 11 cases (78.57%) and a partial remission in No. 3 cases (21.43%). In No. 18 disinfectant, We have obtained a complete disappearance of the drawback in No. 16 (88.8%) cases and a partial disappearance in No. 2 (11.2%) cases. Only in the case of the preservatives (No. 3 single and 16 associations), we have obtained a total remission of the interferences in all cases. For the neutralization, some classic neutralizers (albumin, p-aminobenzoic acid, beta-lactamase, cysteine, Ca+2, egg yolk, Fe+3, heparin, hydroxylamine, thymidine, Tween 20) and a new neutralizing agent (ascorbic acid) were employed. Thus, it is necessary to find suitable neutralizing agents or to research new types of filtering membranes. In the meantime, the production of chemo-antibiotic agents should be carried out according to stingent criteria of asepsis.
Negretti
F
F
Facoltà di Farmacia, Università degli Studi di Milano.
D000890:Anti-Infective Agents / Q000592:standards*; D001681:Biological Assay; D004340:Drug Contamination / Q000517:prevention & control; D014462:Ultrafiltration
D000890:Anti-Infective Agents