Impact of deep freezing on the stability of 25 mg/ml vancomycin ophthalmic solutions

Abstract

For the treatment of certain eye infections, ophthalmic solutions 'laced' with 25 mg/ml vancomycin are sometimes prepared. Their physical and chemical stability and the maintenance of their sterility were studied after deep freezing at -20 +/- 2 degrees C and thawing, followed or not by refrigeration for 48 h at 4 +/- 2 degrees C. Physical and chemical analysis comprised visual inspection turbidity, determination of pH and osmolality, and assay of vancomycin by high performance liquid chromatography with ultraviolet detection. For microbiological analysis a 25 mg/ml vancomycin ophthalmic solution was filtered through two membranes and cultured on trypticase-soy and Sabouraud-glucose solid media. Any colonies were then counted. These physical, chemical and microbiological analyses demonstrated the stability of 25 mg/ml vancomycin ophthalmic solutions in 5% glucose deep frozen at -20 +/- 2 degrees C for 3 months. The vancomycin concentration varied by no more than 5% of the initial concentration, and no breakdown product was evidenced. Neither pH (mean=3.8 +/- 0.1) nor osmolality (mean=318.3 +/- 5.6 mOsm/kg) varied significantly, and remained compatible with intraocular administration. No particle or bacterial combination was found in the course of the study. The thawing procedure (at ambient temperature or under warm running water from a tap) did not modify the stability of the eye drops. Likewise, storage in a refrigerator for 48 h after thawing did not modify stability. The advantage of storing vancomycin 25 mg/ml ophthalmic solutions for 3 months in deep freeze is that a stock of chemically and microbiologically controlled preparations can be held ready for administration to patients, thereby allowing prompter dispensing, as the eye drops are not made up extemporaneously, while the improved control over production ensures that patients receive solutions of constant quality, as every batch prepared is systematically inspected.