51 ANTIMICROBIAL EFFECTIVENESS TESTING
Antimicrobial prervatives are substances added to nonsterile dosage forms to protect them from microbiological growth or from microorganisms that are introduced inadvertently during or subquent to the manufacturing process. In the ca of sterile articles packaged in multiple-do containers, antimicrobial prervatives are added to inhibit the growth of microorganisms that may be introduced from repeatedly withdrawing individual dos.
Antimicrobial prervatives should not be ud as a substitute for good manufacturing practices or solely to reduce the viable microbial population of a nonsterile product or control the presterilization bioburden of multido formulations during manufacturing. Antimicrobial prervatives in compendial dosage forms meet the requirements for Added Substances under 孔雀英文Ingredients and Process in the General Notices.
All uful antimicrobial agents are toxic substances. For maximum protection of patients, the concentration of the prervative shown to be effective in the final packaged product should be below a level that may be toxic to human beings.
The concentration of an added antimicrobial prervative can be kept at a minimum if the active ingredients of the formulation posss an intrinsic antimicrobial activity. Antimicrobial effectiveness, whether inherent in the product or whether produced becau of the addition of an antimicrobial prervative, must be demonstrated for all injections packaged in multiple-do containers or for other products containing antimicrobial prervatives. Antimicrobial effectiveness must be demonstrated for multiple-do topical and oral dosage forms and for other dosage forms such as ophthalmic, otic, nasal, irrigation, and dialysis fluids (e Pharmaceutical Dosage Forms 1151).
This chapter provides tests to demonstrate the effectiveness of antimicrobial protection. Added antimicrobial prervatives must be declared on the label. The tests and criteria for effectiveness apply to a product in the original, unopened container in which it was distributed by the manufacturer.
张驰新PRODUCT CATEGORIES
For the purpo of testing, compendial articles have been divided into four categories (e Table 1). The criteria of antimicrobial effectiveness for the products are a function of the route of administration.
Table 1. Compendial Product Categories
Category | Product Description |
1 | Injections, other parenterals including
emulsions, otic products, sterile nasal
products, and ophthalmic products made
with aqueous bas or vehicles. |
wrod2 | Topically ud products made with aqueous
bas or vehicles, nonsterile nasal products,
and emulsions, including tho applied
to mucous membranes. |
3 | coinOral products other than antacids, made with
aqueous bas or vehicles. 怜悯的意思 |
4 | Antacids made with an aqueous ba. |
| |
shangri laTEST ORGANISMS
U cultures of the following microorganisms1: Candida albicans (ATCC No. 10231), Aspergillus niger (ATCC No. 16404), Escherichia colispecial是什么意思 (ATCC No. 8739), Pudomonas aeruginosaaeroplanes (ATCC No. 9027), and Staphylococcus aureus (ATCC No. 6538). The viable microorganisms ud in the test must not be more than five passages removed from the original ATCC culture. For purpos of the test, one passage is defined as the transfer of organisms from an established culture to fresh medium. All transfers are counted. In the ca of organisms maintained by ed-lot techniques, each cycle of freezing, thawing, and revival in fresh medium is taken as one transfer. A ed-stock technique should be ud for long-term storage of cultures. Cultures received from the ATCC should be resuscitated according to directions. If grown in broth, the cells are pelleted by centrifugation. Resuspend in 1/20th the volume of fresh maintenance broth, and add an equal volume of 20% (v/v in water) sterile glycerol. Cells grown on agar may be scraped from the surface into the 10% glycerol broth. Dispen small aliquots of the suspension into sterile vials. Store the vials in liquid nitrogen or in a mechanical freezer at no more than 50. When a fresh ed-stock vial is required, it may be removed and ud to inoc
ulate a ries of working cultures. The working cultures may then be ud periodically (each day in the ca of bacteria and yeast) to start the inoculum culture.
MEDIA
All media ud in the test must be tested for growth promotion. U the microorganisms indicated above under Test Organisms.
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PREPARATION OF INOCULUM
Preparatory to the test, inoculate the surface of a suitable volume of solid agar medium from a recently revived stock culture of each of the specified microorganisms. The culture conditions for the inoculum culture are described in Table 2 in which the suitable media are Soybean–Cain Digest or Sabouraud Dextro Agar Medium (e Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62).
To harvest the bacterial and C. albicans cultures, u sterile saline TS, washing the surface growth, collecting it in a suitable vesl, and adding sufficient sterile saline TS to obtain a microbial count of about 1 × 108 colony-forming units (cfu) per mL. To harvest the cells of A. niger, u sterile saline TS containing 0.05% of polysorbate 80, and add sufficient sterile saline TS to obtain a count of about 1 × 108 cfu per mL.
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