Physicochemical Characterization of 9-Aminocamptothecin in Aqueous Solutions
| Autor: | Deval Patel, Shahidur Rahman, Michalakis Savva |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Chemistry
Pharmaceutical Inorganic chemistry Enthalpy Pharmaceutical Science Aquatic Science chemistry.chemical_compound Deprotonation Drug Discovery Organic chemistry Solubility Ecology Evolution Behavior and Systematics Aqueous solution Ecology Hydrolysis Quinoline Temperature Free base General Medicine Hydrogen-Ion Concentration Solutions Partition coefficient chemistry Thermodynamics Camptothecin Aminocamptothecin Agronomy and Crop Science Research Article |
| Zdroj: | AAPS PharmSciTech. 15:223-229 |
| ISSN: | 1530-9932 |
| DOI: | 10.1208/s12249-013-0046-y |
| Popis: | The present manuscript provides a detailed physicochemical and thermodynamic characterization of 9-aminocamptothecin (9AC) which can be used as a tool to develop novel formulation strategies for optimum pharmacological activity. The pKa of 9AC was determined to be 2.43 at 37°C, while the basicity of quinoline nitrogen of 9AC was found to decrease with increasing temperature due to a positive enthalpy of deprotonation of 10.36 kJ mol(-1). The equilibrium solubility as well as the intrinsic solubility of the drug was found to increase with increasing temperature and decreasing pH. The enthalpies of solution of unionized and ionized forms of 9AC obtained from isothermal and iso-pH equilibrium solubility measurements were found to be 36.01 and 24.72 kJ mol(-1), respectively. Equilibrium hydrolysis studies revealed the hydrolytic susceptibility of 9AC with only 14% of active lactone species remaining at physiological pH 7.4. The intrinsic partition coefficient log P of the free base, 9AC-lactone, was estimated to be 1.28 (a characteristic of molecules suitable for oral absorption). The estimated pKa and log P values of 9AC, combined with its increased solubility at lower pH, are features that can be utilized to develop novel drug delivery systems to optimize the antitumor activity of 9AC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink