Perks Stephen, Robertson Sherryl, Haywood Alison, Glass Beverley
Townsville General Hospital, QLD, Australia.
Int J Pharm Pract. 2012 Feb;20(1):4-8. doi: 10.1111/j.2042-7174.2011.00155.x. Epub 2011 Aug 19.
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.
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.
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.
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.
氯氮平是一种用于治疗精神分裂症的非典型抗精神病药物。鉴于患者情况，氯氮平重新包装成剂量给药辅助器具（DAA）的比例很高。由于医院药剂师报告称，重新包装到DAA中的氯氮平退回片剂出现变色情况，本研究的目的是评估重新包装到DAA中的这些片剂的化学、物理和光稳定性。
将氯氮平片剂重新包装到DAA中，并在可控室温（25±1°C；相对湿度（RH）60±1.5%）和加速条件（40±1°C；RH 75±1.5%）下，对其进行为期6周的物理化学稳定性评估。此外，根据国际协调会议（ICH）指南进行光稳定性研究。
在所有储存条件下，包括光稳定性（ICH条件）下，均确认了化学稳定性，氯氮平含量在英国药典（BP）规定的90 - 110%范围内。虽然在室温下的所有测试（重量均匀度、硬度、脆碎度、崩解度和溶出度）中均确认了物理稳定性，但在加速条件下，崩解度测试未达到BP要求。然而，随后的溶出度测试成功，85%的氯氮平在45分钟内溶解。
本研究表明，氯氮平正确重新包装后，其物理和化学稳定性可维持6周。由于未观察到片剂变色，推测所收到的报告是患者处理不当所致。基于这些发现，建议告知患者正确处理和储存其DAA的方法。
