Engineering fast dissolving sodium acetate mediated crystalline solid dispersion of docetaxel

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery

Background:

• Docetaxel (DXT) is a BCS class II hydrophobic drug with poor solubility.
• Enhancing DXT solubility and bioavailability is crucial for improving its therapeutic efficacy.
• Crystalline solid dispersion (CSD) is a promising strategy for improving the delivery of hydrophobic drugs.

Purpose of the Study:

• To engineer a novel crystalline solid dispersion (CSD) of docetaxel (DXT) using sodium acetate (SA).
• To characterize the CSD of DXT and evaluate its physicochemical properties.
• To assess the cytotoxicity and safety profile of the novel CSD formulation.

Main Methods:

• Docetaxel (DXT) was dispersed in sodium acetate (SA) solution and freeze-dried to form CSD.
• Characterization involved DSC, PXRD, LC-MS/MS, SEM, TEM, QCM-D, and DLS.
• Cytotoxicity was evaluated using MTS assay on breast cancer and normal cell lines.

Main Results:

• The CSD of DXT in SA was successfully synthesized, confirmed by DSC, PXRD, SEM, and TEM.
• The CSD exhibited a high yield (95.2%) and drug loading (6.52% w/w).
• CSD rapidly formed a nanosuspension with enhanced dissolution rate; SA was non-cytotoxic to normal cells.

Conclusions:

• The novel CSD formulation of DXT enhances drug dissolution and bioavailability.
• The CSD process demonstrates improved safety by utilizing a non-cytotoxic carrier.
• This CSD approach holds potential for other hydrophobic drugs to improve safety and efficacy.