DEVELOPMENT OF METHODS FOR MICROBIAL RECOVERY: PHARMACEUTICAL DOSAGE FORMS INCLUDING DRUGS WITH ANTIMICROBIAL PROPERTIES (STUDY III)

Mostafa Essam Eissa* and Ahmed Mohamed Mahmoud

ABSTRACT

Bioburden determination and detection in the drug products is a crucial attribute in pharmaceutical manufacturing industry that affects both the patients and the reputation of business holders. Establishment and verification of the sensitivity for bioburden detection and enumeration in the dosage forms is critical in minimizing the potential hazard of delivering unsafe products with masked contamination to the market. In the present study, selected group of non-sterile dosage forms – including drugs with known antimicrobial properties - were tested for the ability to recover low level inoculums of pharmacopeial standard strains after applying specific neutralization and processing steps. The neutralization techniques included dilution, filtration, chemical neutralizers or combination of two or more of them together in a single procedure. Preliminary test was conducted to ensure non toxicity of the neutralization media or processes. The average combined microbial recovery of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans (20–25°C), C. albicans (30–35°C) and Aspergillus niger (20–25°C) and A. niger (30–35°C) from all tested pharmaceutical dosage forms was 0.89±0.36, 0.85±0.27, 0.94±0.47, 0.85±0.28, 0.80±0.35, 0.95±0.40 and 0.85±0.32 respectively. The tested products passed the criteria of microbial enumeration and detection of specified microorganisms, with exception of one topical antimicrobial cream with fungi, oral Azithromycin capsule with bacteria, Sodium Risedronate tablet with Pseudomonas aeruginosa (in one neutralization trial without chemical neutralizer) and oral Nifuroxazide capsule with Staphylococcus aureus. Interestingly, microbial recovery of B. subtilis, C. albicans and A. niger from tested products were significantly correlated with each other using Pearson correlation matrix.

Keywords: Bioburden determination and detection, non-sterile dosage forms, standard strains, neutralization techniques, correlation.