Stability of a 50 mg/mL Ceftazidime Eye-Drops Formulation

Eric Gautier,Thomas Briot,Justine Saillard,Caroline Deshayes,Frederic Lagarce,Sandy Vrignaud

doi:10.1515/pthp-2018-0025

Abstract

Abstract Background Microbial keratitis are severe infectionsgenerally linked to risk factors. High-doses antibiotic eye-drops could be required to avoid severe complications. In such cases, hospital pharmacists are in charge of their production given the lack of such formulations on the market. The stability of these antibiotic eye-drops is generally limited to a couple of days and publications generally do not describe addition of microbial preservatives even though it is a European Pharmacopeia requirement. The aim of this study was to describe a new ceftazidime eye-drops formulation at 50 mg/mL with a antimicrobial additive, benzalkonium chloride at 0.04 mg/mL. Methods Physico-chemical studies of this new formulation were performed by a stability indicating HPLC-UV method validated according to ICH standards, osmolality measurements, pH monitoring and visual examinations. Antimicrobial preservative efficacy was evaluated according to the method from the European Pharmacopeia. Results After 75 days at −20 °C followed by 7 days at 4 °C, or after 7 days at 4 °C, the eye-drops were stable. A degradation trend was finally observed at day 14 at 4 °C. Conclusions A new ceftazidime eye-drops formulation is proposed with a stability of 7 days. Outpatients do not need to return to the hospital pharmacy for repeat dispensing, thus possibly improving treatment compliance.

Highlights

Microbial keratitis, a suppurative corneal infiltrate associated with bacterial colonization, is a severe infection generally linked to a risk factor, such as contact or cosmetic lenses, ocular disease, eye surgery or immunodepression [1,2,3].Bacterial keratitis requires instituting a rapid and effective antibiotic eye-drops regime to avoid severe complications such as visual impairment, corneal opacity, endophthalmitis or in the worst case, visual loss
A new ceftazidime eye-drops formulation is proposed with a stability of 7 days
Outpatients do not need to return to the hospital pharmacy for repeat dispensing, possibly improving treatment compliance

Summary

Introduction

A suppurative corneal infiltrate associated with bacterial colonization, is a severe infection generally linked to a risk factor, such as contact or cosmetic lenses, ocular disease, eye surgery or immunodepression [1,2,3].Bacterial keratitis requires instituting a rapid and effective antibiotic eye-drops regime to avoid severe complications such as visual impairment, corneal opacity, endophthalmitis or in the worst case, visual loss. Treatment, based on high-dose antibiotics, must be started without delay after clinical presentation [4]. Antibiotics used in these circumstances could be amikacin, cefazolin, ceftazidime, gentamycin, ticarcillin or vancomycin. High-doses antibiotic eyedrops could be required to avoid severe complications In such cases, hospital pharmacists are in charge of their production given the lack of such formulations on the market. Hospital pharmacists are in charge of their production given the lack of such formulations on the market The stability of these antibiotic eye-drops is generally limited to a couple of days and publications generally do not describe addition of microbial preservatives even though it is a European Pharmacopeia requirement. Antimicrobial preservative efficacy was evaluated according to the method from the European Pharmacopeia

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