Pharmaceutical development of a parenteral lyophilized formulation of the antimetastatic ruthenium complex NAMI-A
| Autor: | Auke Bult, Antonella Flaibani, J. J. Kettenes-van den Bosch, Gianni Sava, M. Bouma, Bastiaan Nuijen, Alberto Perbellini, Herre Talsma, Jos H. Beijnen, M.J. van Steenbergen |
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| Rok vydání: | 2002 |
| Předmět: |
Aqueous solution
Chromatography Stereochemistry Chemistry Pharmaceutical Pharmaceutical Science chemistry.chemical_element Antineoplastic Agents Hydrochloric acid Pharmaceutical formulation Ruthenium Dosage form Freeze-drying chemistry.chemical_compound Freeze Drying chemistry Organometallic Compounds Ruthenium Compounds Technology Pharmaceutical Dimethyl Sulfoxide Infusions Parenteral Chemical stability Neoplasm Metastasis Solubility |
| Zdroj: | International Journal of Pharmaceutics. 248:247-259 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/s0378-5173(02)00459-3 |
| Popis: | This paper describes the development of a stable pharmaceutical dosage form for NAMI-A, a novel antimetastatic ruthenium complex, for Phase I testing. NAMI-A drug substance was characterized using several spectrometric and chromatographic techniques. In preformulation studies, it was found that NAMI-A in aqueous solution was not stable enough to allow sterilization by moist heat. The effect of several excipients on the stability of the formulation solution was investigated. None of them provided sufficient stability to allow long-term storage of an aqueous solution of NAMI-A. Therefore, a lyophilized product was developed. Five different formulations were prepared and subjected to thermogravimetric (TG) analysis and stability studies at various conditions for 1 year. Minimal degradation during the production process is achieved with a formulation solution of pH 3-4. Of the acids tested, only hydrochloric acid (HCl 0.1 mM) both stabilized the formulation solution and was compatible with the lyophilized product. This product was stable for at least 1 year when stored at -20 degrees C, 25 degrees C/60% relative humidity (RH) and 40 degrees C/75% RH, and was also photostable. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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