Drug-Phospholipid Co-Amorphous Formulations: The Role of Preparation Methods and Phospholipid Selection

Area of Science:

• Materials Science
• Pharmaceutical Technology
• Drug Delivery Systems

Background:

• Poorly water-soluble drugs pose challenges in pharmaceutical formulations.
• Co-amorphous phospholipid systems (CAPSs) offer a promising approach to enhance drug solubility and bioavailability.
• Limited knowledge exists on the formation and stability of CAPSs with a diverse range of drugs and phospholipids.

Purpose of the Study:

• To explore the formation of co-amorphous phospholipid systems (CAPSs) with celecoxib, furosemide, nilotinib, and ritonavir.
• To investigate the impact of different preparation methods (ball milling, quench cooling, solvent evaporation) on CAPS formation and stability.
• To evaluate the dissolution behavior and physical stability of the developed CAPSs.

Main Methods:

• Co-amorphous phospholipid systems (CAPSs) were prepared using ball milling (BM), quench cooling (QC), and solvent evaporation (SE) methods.
• Equimolar drug-to-phospholipid (PL) ratios were initially screened, followed by investigation of various molar ratios (e.g., 1.5:1) and excess PL.
• Solid-state characterization included X-ray powder diffraction (XRPD), polarized light microscopy (PLM), and differential scanning calorimetry (DSC); physical stability was assessed at 0% and 75% RH.

Main Results:

• Solvent evaporation (SE) was the most consistent method for preparing CAPSs with celecoxib (CCX), furosemide (FUR), and ritonavir (RIT).
• CAPSs exhibited enhanced dissolution for CCX and RIT, with phospholipids providing slight precipitation inhibition.
• Physical stability was significantly improved in SE-prepared CAPSs, especially at a 1.5:1 molar ratio or with excess PL.

Conclusions:

• Co-amorphous phospholipid systems (CAPSs) can be effectively prepared using the solvent evaporation method, supporting their use in screening processes.
• These systems allow for relatively high drug loads compared to traditional drug-polymer systems.
• Drug selection, preparation method, and phospholipid type are critical factors for developing stable and effective CAPSs.