Engineering micro- and nanosized pharmaceutical salt crystals using high-pressure homogenization.

Area of Science:

• Pharmaceutical Science
• Materials Science
• Chemical Engineering

Background:

• Conventional crystallization methods for pharmaceutical salts can be inefficient and environmentally taxing.
• Developing scalable and sustainable synthesis routes for improved drug delivery is crucial.

Purpose of the Study:

• To investigate high-pressure homogenization (HPH) as a novel, green manufacturing technique for pharmaceutical salt synthesis.
• To characterize the resulting salts and evaluate their dissolution performance.

Main Methods:

• Utilized high-pressure homogenization (HPH) for salt formation using ketoconazole (KTZ) and oxalic acid (OA) with various stabilizers.
• Employed X-ray powder diffraction (XRPD), FT-IR spectroscopy, and scanning electron microscopy (SEM) for structural and morphological analysis.
• Conducted dissolution studies at pH 4.4 to assess drug release profiles.

Main Results:

• Successfully synthesized novel KTZ:OA pharmaceutical salts via HPH, confirmed by XRPD and FT-IR, indicating proton transfer and hydrogen bonding.
• Achieved significant particle size reduction to the submicron range with controlled crystal morphology, tunable via stabilizer concentration and temperature.
• Demonstrated substantially improved dissolution rates, with up to 80% drug release within 15 minutes for HPH-processed salts compared to bulk KTZ.

Conclusions:

• High-pressure homogenization (HPH) is a versatile, solvent-free, and continuous manufacturing platform for producing high-purity pharmaceutical salts.
• HPH processing leads to superior dissolution performance, offering a transformative approach for solid-state drug formulation.
• This method presents a scalable and environmentally sustainable alternative to traditional crystallization techniques in pharmaceutical development.