Physicochemical Characterization of 9-Aminocamptothecin in Aqueous Solutions
Journal Title: AAPS PharmSciTech - Year 2014, Vol 15, Issue 1
Abstract
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.
Authors and Affiliations
Shahidur Rahman, Deval Patel, Michalakis Savva
Keywords
Related Articles
- EP ID EP682356
- DOI 10.1208/s12249-013-0046-y
- Views 86
- Downloads 0
Retraction Note: Design and Formulation Technique of a Novel Drug Delivery System for Azithromycin and its Anti-Bacterial Activity Against Staphylococcus aureus
The online version of the original article can be found at 10.1208/s12249-013-9993-6.
Acceptance Probability (Pa) Analysis for Process Validation Lifecycle Stages
This paper introduces an innovative statistical approach towards understanding how variation impacts the acceptance criteria of quality attributes. Because of more complex stage-wise acceptance criteria, traditional proc...
Effect of Porosity on Strength Distribution of Microcrystalline Cellulose
Fracture strength of pharmaceutical compacts varies even for nominally identical samples, which directly affects compaction, comminution, and tablet dosage forms. However, the relationships between porosity and mechanica...
Assessing Mixing Quality of a Copovidone-TPGS Hot Melt Extrusion Process with Atomic Force Microscopy and Differential Scanning Calorimetry
Atomic force microscopy (AFM) and modulated differential scanning calorimetry (mDSC) were used to evaluate the extent of mixing of a hot melt extrusion process for producing solid dispersions of copovidone and D-α...
Targeted Gene Delivery to MCF-7 Cells Using Peptide-Conjugated Polyethylenimine
The online version of this article (doi:10.1208/s12249-014-0208-6) contains supplementary material, which is available to authorized users.