Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, amorphous solid dispersion, bead coating, spray drying, drug loading screening, drug-polymer interactions, physical stability, ACTIVE PHARMACEUTICAL INGREDIENTS, HOT-MELT EXTRUSION, PHYSICAL STABILITY, GLASS-TRANSITION, PHASE-BEHAVIOR, ORAL BIOAVAILABILITY, SOLVENT INFLUENCE, CRYSTALLIZATION, MISCIBILITY, FORMULATION, drug–polymer interactions, 1S06120N|1S06122N#55274084, 1115 Pharmacology and Pharmaceutical Sciences, 3214 Pharmacology and pharmaceutical sciences

Abstract:

Despite the fact that an amorphous solid dispersion (ASD)-coated pellet formulation offers potential advantages regarding the minimization of physical stability issues, there is still a lack of in-depth understanding of the bead coating process and its value in relation to spray drying. Therefore, bead coating and spray drying were both evaluated for their ability to manufacture high drug-loaded ASDs and for their ability to generate physically stable formulations. For this purpose, naproxen (NAP)-poly(vinyl-pyrrolidone-co-vinyl acetate) (PVP-VA) was selected as an interacting drug-polymer model system, whilst naproxen methyl ester (NAPME)-PVP-VA served as a non-interacting model system. The solvent employed in this study was methanol (MeOH). First, a crystallization tendency study revealed the rapid crystallization behavior of both model drugs. In the next step, ASDs were manufactured with bead coating as well as with spray drying and for each technique the highest possible drug load that still results in an amorphous system was defined via a drug loading screening approach. Bead coating showed greater ability to manufacture high drug-loaded ASDs as compared to spray drying, with a rather small difference for the interacting drug-polymer model system studied but with a remarkable difference for the non-interacting system. In addition, the importance of drug-polymer interactions in achieving high drug loadings is demonstrated. Finally, ASDs coated onto pellets were found to be more physically stable in comparison to the spray dried formulations, strengthening the value of bead coating for ASD manufacturing purposes.