Preservative efficacy in cefuroxime and ceftazidime eye drop formulations

Abstract

The efficacy of various common antimicrobial preservatives was tested in eye drop formulations containing the cephalosporin antibiotics cefuroxime and ceftazidime. The British Pharmacopoeia test for the efficacy of antimicrobial preservatives was used and the formulations were challenged with Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. The survival of organisms was monitored over 14 days. Cefuroxime sodium, 50 mg/ml, was studied in simple aqueous solution, and dissolved in an artificial tear formulation, Sno Tears (Smith and Nephew Pharmaceuticals), which contains benzalkonium chloride 0.004% w/v. Ceftazidime (50 mg/ml) was also studied in these two vehicles and, in addition, in a phenylmercuric acetate solution (0.002% w/v) and chlorhexidine acetate (0.02% w/v). Cefuroxime and ceftazidime contributed little, in the short-term, towards a microbicidal preservative effect in the unpreserved aqueous formulations, even against organisms for which they were active. Cefuroxime was adequately preserved in a vehicle of Sno Tears, which contains benzalkonium chloride as the antimicrobial preservative. Ceftazidime was less well preserved in this vehicle, but it was superior to phenylmercuric acetate (0.002% w/v) or chlorhexidine acetate (0.02% w/v).

Stability of ceftazidime in a viscous eye drop formulation

“…Ceftazidime, a third‐generation cephalosporin antibiotic, has been formulated as an eye drop (1) in an artificial tear solution containing polyvinyl alcohol ( Sno Tears ). The formulation was shown to be preserved adequately by challenging with micro?organisms (2), whereas some other vehicles studied were unsatisfactory (2, 3).…”

Chemical and microbiological stability of diluted ceftazidime in three different solutions under three storage temperatures over a 28 day period

“…The solution was brought to volume with sterile water, and a 100 µL aliquot was transferred to a 10 mL flask and brought to volume with sterile water, for a final concentration of 0.2 mg/mL. This was further diluted to generate a standard curve, which was repeated weekly before sample analysis 15 . The lower limit of detection was 0.01 mg/mL based on sensitivity of the instrument.…”

“…14 A CAZ standard [ceftazidime pentahydrate, United States Pharmacopeia (USP) reference standard, Sigma-Aldrich; St Louis, MO, USA] was prepared by weighing 100 mg of the powder into a 5 mL volumetric flask and 1 mL of 1.2% aqueous sodium carbonate was added to aid in dissolution. 14,15 The solution was brought to volume with sterile water, and a 100 µL aliquot was transferred to a 10 mL flask and brought to volume with sterile water, for a final concentration of 0.2 mg/mL. This was further diluted to generate a standard curve, which was repeated weekly before sample analysis.…”

“…This was further diluted to generate a standard curve, which was repeated weekly before sample analysis. 15 The lower limit of detection was 0.01 mg/mL based on sensitivity of the instrument. Samples were equilibrated to room temperature and a 100 µL aliquot of the compounded solution was diluted with sterile water to an approximate concentration of 0.1 mg/mL for HPLC analysis.…”

Near-patient stability studies

“…Finally, microbiological tests may be required on non-sterile products or multi-use sterile products, e.g. antimicrobial challenge testing (13,32,42).…”