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

Despite advances in the field of multidrug formulations, developing and manufacturing them still poses substantial challenges, particularly for drugs with low aqueous solubility. Here, this critical issue was addressed by engineering amorphous multidrug formulations with optimized performance at the site of absorption using the spray drying technique. Formulations containing atazanavir and ritonavir, alone or in combination, were produced by spray drying. Excipient content in aqueous solution was optimized to generate a stable feed suspension of amorphous particles with controlled particle size. The powder formulations were characterized by powder X-ray diffraction (PXRD), thermal analysis, laser diffraction, and scanning electron microscopy (SEM). The drug content was assayed, and a dissolution study was performed. Dynamic light scattering was used to measure particle size of the colloidal phase in the feed suspension and after dissolution of powder. A stability study was conducted at 25 °C/60 % RH and 40 °C/75 % RH condition for 4 weeks. DSC and PXRD confirmed the formulations to be amorphous. Drug content in the spray-dried formulations ranged from 98 to 108 %. Laser diffraction measured the particles to be from 5-10 µm and SEM showed they had wrinkled and irregularly shaped surfaces. The particle size of the colloidal phase formed upon dissolution of combination formulation was stable at 900 nm over 120 min. The formulations remained amorphous under both studied conditions throughout the stability study period. These findings highlight the potential of particle engineering, where a mechanistically informed selection of excipients is combined with an appropriate spray-drying process, to achieve highly stable and robust amorphous multidrug formulations -critical for ensuring effective drug performance and patient treatment.