Objectives: Clozapine is an atypical antipsychotic used in the treatment of schizophrenia. Due to the patient profile there is a high rate of repackaging of clozapine into dose administration aids (DAAs). Because of reports from hospital pharmacists about discoloration of returned clozapine tablets that have been repackaged into DAAs, the aim of this study was to evaluate the chemical, physical and photostability of these tablets repackaged into a DAA.
Method: Clozapine tablets were repackaged into DAAs and evaluated for physicochemical stability over a 6-week period at a controlled room temperature (25±1°C; 60±1.5% relative humidity (RH)) and accelerated conditions (40±1°C; 75±1.5% RH). In addition, photostability studies were performed according to the International Committee on Harmonisation (ICH) guidelines.
Key findings: Chemical stability was confirmed for all storage conditions, including for those photostability (ICH conditions), with the clozapine content occurring within the British Pharmacopoeial (BP) range of 90-110%. Although the physical stability was confirmed for all tests at room temperature (weight uniformity, hardness, friability, disintegration and dissolution), under accelerated conditions the disintegration test did not meet BP requirements. However, the subsequent dissolution test was successful with 85% of clozapine dissolving in 45min.
Conclusions: This study illustrates that clozapine, when correctly repackaged, maintains its physical and chemical stability for 6 weeks. As no discoloration of the tablets was observed, it is assumed that the reports received were as a result of improper handling by patients. Based on these findings, it is recommended that patients be advised on the correct handling and storage of their DAAs.
© 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society.