Stability study of an injectable hospital preparation of naloxone hydrochloride as part of a clinical trial

Introduction

The injectable hospital preparation of naloxone hydrochloride dosed at 0.4 mg/ml is administered by parenteral route as part of a multicentric double-blind clinical trial. This clinical research focuses on the evaluation of efficacity of the administration of naloxone 0.4 mg or placebo (Sodium chloride 0.9%) in the reduction of severe dysfunction of post-critical tonic-clonic seizures. To meet regulatory requirements and have ready to use preparation with an expiration date, a stability study was realised.

[[Methods
This hospital preparation was realised in an isolator under aseptic conditions associated with sterilizing filtration. Bottles of glass vials type II (5 ml filled to 1 ml with of solution) prepared were stored in a climatic chamber at 25°C ± 2°C. To assess the stability of the finished product, the physicochemical controls (dosage of naloxone by liquid chromatography, sodium concentration, measurement of pH, osmolality, particle sub-visible particles) and microbiologicals (bacterial endotoxin and sterility) were realised during one year from a pilot batch.

Results and discussion

Throughout the stability study, neither significant decrease of naloxone concentration and sodium concentration nor pH and osmolality variation were observed. The variation of the concentration of naloxone remaining relative to the initial concentration was between 98.9% and 103.6%. The sub-visible particles, the bacterial endotoxin and sterility were in accordance with the European Pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation.

Conclusion

The hospital preparation was stable over one year at 25°C ± 2°C ensuring to safe a parenteral administration for human as part of the clinical trial.

Key words : Naloxone hydrochloride, Hospital preparation, Stability study, Clinical trial, Tonic-clonic seizures.