Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation

Area of Science:

• Pharmaceutical Science
• Solid-State Chemistry
• Oncology

Background:

• Dacarbazine (DTIC) is crucial for advanced melanoma but suffers from poor solubility and photosensitivity.
• Photodegradation yields inactive 2-azahypoxanthine (2-AZA), limiting therapeutic effectiveness.
• Current formulations require strategies to enhance DTIC's biopharmaceutical profile.

Purpose of the Study:

• To develop novel Dacarbazine (DTIC) salt and cocrystal forms.
• To enhance DTIC's solubility and dissolution rate.
• To minimize DTIC's photodegradation.

Main Methods:

• Cocrystallization techniques using aliphatic carboxylic acids.
• Structural characterization via Single Crystal X-ray Diffraction (SCXRD), Powder X-ray Diffraction (PXRD), FT-IR, ¹H NMR, Thermogravimetric Analysis (TG), and Differential Scanning Calorimetry (DSC).

Main Results:

• Successfully prepared two DTIC salts, two cocrystals, and one salt-cocrystal.
• Achieved significant solubility enhancement (up to 19-fold) and increased intrinsic dissolution rates (1.3 to 22-fold).
• These new forms demonstrated a positive impact on reducing DTIC photodegradation in solution.

Conclusions:

• Novel DTIC salts and cocrystals significantly improve solubility and dissolution.
• These enhanced solid forms hold promise for overcoming Dacarbazine's biopharmaceutical limitations.
• The developed forms could lead to more effective melanoma treatments.