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PubMed · 17010545

EO-9 bladder instillations: formulation selection based on stability characteristics and in vitro simulation studies.

S C van der Schoot·L D Vainchtein·J H Beijnen·A Gore·D Mirejovsky·L Lenaz·B Nuijen
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Abstract

A bladder instillation of EO-9 (EOquin) is currently used in phase II clinical trials for the treatment of superficial bladder cancer. Three alternative formulations were developed to improve its pharmaceutical properties and clinical acceptability. Freeze-dried products composed of EO-9, 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD), tri(hydroxymethyl) aminomethane (Tris), and sodium bicarbonate (NaHCO(3)) were tested. Selection of one formulation for further development was based on stability studies. These studies comprised stability of the freeze-dried products, stability after reconstitution and dilution and stability during bladder instillation in an experimental set-up. The stability study of the freeze-dried products showed that the formulation composed of EO-9/HPbetaCD/Tris (4/600/1mg/vial) was most stable. After reconstitution and dilution all products were stable for at least 8h. The product composed of EO9/HPbetaCD/NaHCO(3) (4/600/20mg/vial) was the least stable product both as freeze-dried formulation and after reconstitution and dilution. The bladder instillation simulation experiment showed that all products were stable when mixed with urine of pH 8 and unstable in urine of pH 4 and 6. The degradation products formed in urine were EO-5a and EO-9-Cl. Based on these results, the product composed of EO-9/HPbetaCD/Tris (4/600/1mg/vial) was selected for further pharmaceutical development.

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AziridinesComputer SimulationDrug StabilityDrug StorageIndolequinonesModels, BiologicalUrinary Bladder NeoplasmsJournal Article

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S C van der Schoot, L D Vainchtein, J H Beijnen, A Gore, D Mirejovsky, L Lenaz, B Nuijen. 2006-09-01. EO-9 bladder instillations: formulation selection based on stability characteristics and in vitro simulation studies.. https://doi.org/10.1016/j.ijpharm.2006.08.031

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