Stability of fortified cefazolin ophthalmic solutions prepared in artificial tears containing surfactant-based versus oxidant-based preservatives.
OBJECTIVE
The aim of this study was to investigate the stability of fortified cefazolin sodium ophthalmic solutions (50 mg mL⁻¹) extemporaneously prepared in commercial artificial tears containing 2 different types of preservatives, namely the surfactants and oxidants.


METHODS
Fortified cefazolin sodium solutions were prepared by reconstituting cefazolin for injection with sterile water and further diluted with Tears Naturale II or Natear, 2 commercial artificial tears containing polyquaternium-1 and sodium perborate, respectively, as preservatives. The solutions were then kept at room temperature (28°C) or in the refrigerator (4°C). During the 28-day period, the formulations were periodically examined for the physical appearance, pH, and the remaining drug concentrations. The antibacterial potency was evaluated as the minimal inhibitory concentration against Staphylococcus aureus strain ATCC 29923 by broth dilution technique. The activity of the preservatives was demonstrated by antimicrobial effectiveness tests. On day 28, the microbial contamination in the preparations was tested.


RESULTS
The stability profiles of cefazolin solutions prepared in Tears Naturale II, Natear, and water were not different, but they were significantly influenced by the storage temperature. The refrigerated formulations showed no loss of drug and antibacterial potency as well as alteration of physical appearance and pH throughout the 28 days. In contrast, those kept at room temperature showed gradual change in color and odor. The degradation of drug exceeded 10% from day 3 and the decrease of antibacterial potency could be observed at week 3. All cefazolin solutions prepared in artificial tears retained the antimicrobial activity of preservatives and were free from bacterial and fungal contamination throughout the 28-day period of study.


CONCLUSIONS
Cefazolin sodium ophthalmic solutions can be extemporaneously prepared in Tears Naturale II or Natear without the influence from different types of preservatives used in these vehicles. The formulation is physically and chemically stable and retains the antibacterial potency for at least 28 days in the refrigerator.
Rojanarata
Theerasak
T
Faculty of Pharmacy, Silpakorn University , Nakhon Pathom, Thailand. teerasak@su.ac.th
Tankul
Junlathip
J
Woranaipinich
Chayanee
C
Potawanich
Paweena
P
Plianwong
Samarwadee
S
Sakulma
Sirinart
S
Saehuan
Choedchai
C
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002437:Cefazolin / Q000008:administration & dosage / Q000494:pharmacology*; D004340:Drug Contamination; D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D009883:Ophthalmic Solutions / Q000737:chemistry; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D011310:Preservatives, Pharmaceutical / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects; D013501:Surface-Active Agents / Q000378:metabolism / Q000494:pharmacology; D013696:Temperature
D000900:Anti-Bacterial Agents; D009883:Ophthalmic Solutions; D016877:Oxidants; D011310:Preservatives, Pharmaceutical; D013501:Surface-Active Agents; D002437:Cefazolin