| DOI: 10.29090/psa.2025.03.25.4692 | Pharm Sci Asia 2025; 52(3), 385-395 |
Extended stability of extemporaneously prepared cefazolin ophthalmic solutions in preservative-free vehicles under frozen storageNithima Kharomprat1, Suporn Charumanee2, Nantaka Khorana3, Sudaporn Wongwan4*
1 Department of Pharmacy, Phichit Hospital, Pichit, Thailand
2
Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
3
Faculty of Pharmacy, Payap University, Chiang Mai, Thailand
4
Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
This study investigated the chemical and physical stability of extemporaneously prepared fortified cefazolin ophthalmic solutions (50 mg/mL) stored in low-density polyethylene containers under freezer conditions (−18 ± 2 °C) for up to 45 days. Formulations were compounded using cefazolin sodium for injection and five preservative-free vehicles: sterile water for injection, normal saline solution, balanced salt solution, and two commercially available lubricant eye drops—Lubric-Eyes® and VISLUBE®. Cefazolin concentrations were quantified using a validated stability-indicating high-performance liquid chromatographic method with photodiode array detection, employing a C18 column and a mobile phase composed of acetonitrile and 0.1% (v/v) acetic acid in water (22:78, v/v). All formulations retained 94.36%–99.89% of their initial cefazolin concentration throughout the 45-day frozen storage, with no significant changes in pH (5.37–6.70), color, odor, or visible particulates. To simulate outpatient post-dispensing conditions, samples stored frozen for 14 days were thawed at 30 ± 2 °C for 1 hr, then stored under refrigeration (5 ± 3 °C) for an additional 14 days. Cefazolin concentrations during this 28-day period remained within 97.53%–100.38% of initial values, although slight discoloration and mild odor changes were observed from Day 21 onward. In conclusion, the present study demonstrates that frozen storage provides superior stability for cefazolin ophthalmic solutions compared to the studies at refrigeration alone that were previously reported in the literature. Importantly, this study provides the first evidence of the compatibility between cefazolin sodium and preservative-free lubricant-based vehicles, highlighting their potential as patient-friendly alternatives in extemporaneous ophthalmic compounding.
Keyword:
Cefazolin; Drug stability; Ophthalmic solutions; Preservative-free vehicles; Frozen storage
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