Stability of Clozapine Stored in Oral Suspension Vehicles at Room Temperature (2005)

ABSTRACT Rationale: For patients who cannot or will not take medications in tablet form, a liquid formulation of clozapine is required; however, no commercial oral liquid or suspension exists. Objective: To evaluate the stability of a 20 mg/mL clozapine suspension in 6 different suspending vehicles: Ora-Sweet, Ora-Plus, a 1:1 mixture of Ora-Sweet and Ora-Plus, the suspending vehicle used by the Hospital for Sick Children, simple syrup, and a noncommercial vehicle known as Guy’s pediatric mixture. Methods: A reverse-phase, stability-indicating liquid chromatographic method with ultraviolet detection at 230 nm was validated before the study. Validation demonstrated that clozapine could be quantified accurately and reproducibly. On study day 0, 100 mL of a 20 mg/mL clozapine suspension was prepared in each of the 6 suspending vehicles. Each suspension was separated into 3 equal aliquots, which were stored in 60-mL amber plastic containers. All suspensions were stored at room temperature (23°C) without protection from light. On study days 0, 3, 6, 14, 28, and 63, the concentration of clozapine was determined by liquid chromatography, and physical inspection was performed. Results: During the study period, all study samples retained more than 95.0% of their initial concentration. Inspection of chromatograms obtained during the stability study failed to reveal any of the degradation products that had been generated during the assay validation. Conclusion: Suspensions of clozapine (20 mg/mL) prepared in the 6 suspending vehicles used in this study and stored in amber plastic containers at 23°C retained more than 95% of their initial concentration during 63 days of storage, regardless of the suspending vehicle. RESUME Historique : Pour les patients qui ne peuvent ou ne veulent pas prendre de medicaments sous forme de comprimes, une forme liquide de clozapine est donc necessaire; cependant, aucune forme de clozapine liquide ou en suspension n’est offerte dans le commerce. Objectif : Evaluer la stabilite d’une suspension de clozapine a 20 mg/mL dans six differents excipients pour suspension : Ora-Sweet, Ora-Plus, un melange 1:1 d’Ora-Sweet et d’Ora-Plus, l’agent de suspension utilise par le Hospital for Sick Children, un excipient non commercial connu sous le nom de melange pediatrique de Guy, et le sirop simple. Methodes : Une epreuve par chromatographie liquide en phase inverse, indicative de la stabilite, avec detection ultraviolette a 232 nm a ete validee avant l’etude. La validation a montre que la clozapine pouvait etre quantifiee de facon precise et reproductible. Au jour 0 de l’etude, on a prepare 100 mL d’une suspension de clozapine a 20 mg/mL dans chacun des six excipients pour suspension. Chaque preparation de suspension a ete separee en trois aliquots egaux, qui ont ete entreposes dans des contenants de plastique de couleur ambre de 60 mL. Toutes les preparations de suspension ont ete entreposees a la temperature ambiante (23 °C), non protegees de la lumiere. Aux jours 0, 3, 6, 14, 28 et 63 de l’etude, la concentration de clozapine a ete determinee par chromatographie liquide et une inspection physique a ete effectuee. Resultats : Au cours de la periode de l’etude, tous les echantillons ont conserve plus de 95,0 % de leur concentration initiale. L’inspection des chromatogrammes obtenus par l’epreuve de stabilite n’a pu reveler aucun des produits de degradation generes durant la validation du procede d’analyse. Conclusion : Les suspensions de clozapine (20 mg/mL) preparees dans les six excipients pour suspension utilises dans cette etude, puis entreposes dans des contenants de plastique ambres a 23 °C ont conserve plus de 95 % de leur concentration initiale pendant 63 jours d’entreposage, independamment de l’excipient pour suspension utilise.