Pharmaceutical products may be encapsulated in a relatively stable shell for oral consumption. These shells are called capsules and can either be hard-shelled or soft-shelled. Hard-shell capsules are commonly filled with dry powdered ingredients, pellets, or granules. Soft-shell capsules (softgels) are made from gelatin and primarily contain oils or active ingredients that are dissolved or suspended in oil. Both hard and soft-shell capsules may contain colorants, dyes, opaquing, dispersing, or hardening agents, and preservatives. Tablets are solid doses of medicinal substances and may be soluble effervescent, chewable, molded, or compressed.
Traditional methods for testing
Plate count methodology as described in USP <61> is regularly used to test capsules and tablets. Using this methodology, it takes two days for Aerobic Count results, and five days for Yeast and Mold results. When testing for objectionable organisms, it may take several days using selective broths or agars to determine the absence or presence of these bacteria. The colors of the shells and the products and the viscosity of the 1:10 dilution sometimes interfere with the reading of the plates.
Rapid Detection with the BioLumix System
The BioLumix System simplifies testing, expedites time to results, reduces the testing cost and accelerates product release while providing better control of microbial contamination. The system can be used to automate microbial testing with a more cost effective and streamline manner, and reduces the error rates produced by paper-based activity recording and batch data entry. The BioLumix system also helps automate microbiological quality control processes.
To validate the equivalency of the BioLumix system to USP <61> or USP <2021>, over 100 types of capsules, softgels, and tablets were tested with the BioLumix system and plate count methodology at various specified levels. The products were tested for total aerobic microbial count (TAMC), Total yeast and mold count (TYMC), and the absence of E. coli, P. aeruginosa, S. aureus, and Salmonella (objectionable organisms) in 10 grams of product. For each assay, a 1:10 dilution was created by adding 10 grams of product to 90 mL of TSB and further dilutions were performed depending on the desired specified level. Some of the samples were inoculated with various bacteria.
Figure 1 shows the BioLumix curves obtained for the Total Aerobic assay. The purple curve represents an inoculated colored capsule. All the curves along the baseline represent different kind of capsulesthat were not contaminated.
Figure 2 shows the BioLumix curves for the Yeast and Mold assay. The dark blue curve represents an inoculated product. All the curves along the baseline represent different kind of capsules that were not contaminated.
As seen in Figure 3, the BioLumix vial design is separated into two zones: the incubation zone where the sample is present and the detection zone where the reading takes place. Therefore, the system prevents any product interference.
Figure 3 shows two vials that contained dissolved blue capsules. The sample on the right contained bacteria while the sample on the left was clean.
Final results are seen in the BioLumix system roughly 25-40 hours faster than the plate count method in the Total Aerobic Count assay and 40-72 hours faster in the Yeast and Mold assay.
When testing for objectionable organisms, results may be obtained several days sooner than the plate count method. Following the BioLumix protocol, 0.1 mL of the incubated sample in TSB is added to a selective vial and data is collected in the BioLumix instrument for 18-24 hours, depending on the assay. If detection occurs, the sample may be verified with a confirmation assay. This procedure eliminates hours or days waiting for plate results.
The BioLumix system is faster, less labor-intensive, and more sensitive than the plate count method. With an automated certificate of analysis generated within 48 hours, the time-to-results is reduced and allows for quick release of products.
USP <61> MICROBIOLOGICAL EXAMINATION OF NONSTERILE PRODUCTS: MICROBIAL ENUMERATION TESTS
USP <2021> MICROBIAL ENUMERATION TESTS—NUTRITIONAL AND DIETARY SUPPLEMENTS
USP <2022> MICROBIOLOGICAL PROCEDURES FOR ABSENCE OF SPECIFIED MICROORGANISMS—NUTRITIONAL AND DIETARY SUPPLEMENTS