Solubilization of NSC-639829.

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Medicinal Chemistry

Background:

• NSC-639829 is an investigational anti-tumor agent with low intrinsic solubility (approx. 30 ng/ml).
• The drug possesses an ionizable dimethyl aniline group with a pK(a) around 5, allowing for pH-dependent ionization.
• Effective solubilization strategies are crucial for developing this potent anti-tumor compound.

Purpose of the Study:

• To investigate the solubilization of NSC-639829 using a combination of pH control, cosolvents, surfactants, and complexants.
• To determine the optimal conditions for enhancing the solubility of NSC-639829, focusing on its ionized and un-ionized states.
• To evaluate the impact of charged solubilizing agents on drug solubility.

Main Methods:

• Solubilization experiments were conducted using NSC-639829 at pH 1.0, 2.0, and 7.0.
• Various concentrations of cosolvents, surfactants (e.g., sodium lauryl sulfate - SLS), and complexants (e.g., sulfobutylether beta-cyclodextrin - SBEbetaCD) were employed.
• Solubility was measured for both charged and uncharged forms of the drug under different conditions.

Main Results:

• Solubilization was significantly more effective when NSC-639829 was in its ionized form.
• At pH 1.0 and 2.0, where SLS and SBEbetaCD carried a negative charge, solubility enhancements exceeding one million-fold were observed.
• The combination of low pH and charged solubilizing agents dramatically improved drug solubility.

Conclusions:

• Ionization of NSC-639829 is a key factor for achieving high solubility.
• Charged surfactants and complexants, particularly at acidic pH, are highly effective solubilizing agents for NSC-639829.
• These findings provide a promising approach for the formulation and development of NSC-639829 as an anti-tumor therapeutic.