Optimizing amorphous multidrug formulations: A particle engineering approach through spray drying.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery

Background:

• Developing multidrug formulations presents challenges, especially for poorly soluble drugs.
• Amorphous solid dispersions are a strategy to enhance solubility and bioavailability.
• Spray drying offers a scalable method for producing amorphous formulations.

Purpose of the Study:

• To engineer stable amorphous multidrug formulations of atazanavir and ritonavir using spray drying.
• To optimize excipient selection and spray drying parameters for improved performance.
• To evaluate the physical characteristics, drug content, dissolution, and stability of the formulations.

Main Methods:

• Spray drying of atazanavir and ritonavir formulations.
• Characterization using PXRD, thermal analysis, laser diffraction, and SEM.
• Dissolution studies and particle size analysis via DLS.
• Stability testing under accelerated conditions (25°C/60% RH and 40°C/75% RH).

Main Results:

• Spray drying produced stable amorphous formulations with controlled particle size (5-10 µm).
• Formulations exhibited high drug content (98-108%) and maintained amorphous state under stability conditions.
• Dissolution of the combination formulation resulted in stable colloidal particles (~900 nm).

Conclusions:

• Particle engineering via spray drying is effective for creating stable amorphous multidrug formulations.
• Mechanistically informed excipient selection and process optimization are key to robust formulations.
• These engineered formulations hold potential for improved drug performance and patient treatment.