Preparation of seeded granules to improve mechanical properties and various drug loading for pharmaceutical application

Abstract

The present work explores the pharmaceutical application of a novel seeded granulation to develop properties improved, high drug-loaded, and sustained-release tablets using hydroxypropylcellulose (HPC) as a binder. Itraconazole, 4-acetamidophenol, and rifaximin were selected as model drugs. They differ significantly with respect to particle size distribution and solubility. As granulated, the correlation among drug properties, binder characteristics, granulation parameters, and product attributes was discussed. Granulation was performed with 11% HPC-L at a constant impeller tip speed of 4.39 m/s and above. The liquid bridge interaction occurred when coarse particles were granulated along with fine particles. The detachment-reattachment process was responsible for the formation of core-shell seeded granules. Such granules showed good mechanical properties, strength, flowability, compactability, sustained release, high drug-loading, and uniformity. In comparison to conventional granulation, this method is cost-effective, gives better compactability, yields a reduced tablet size at a high dose, and facilitates manufacturability using standard batch granulation. (c) 2021 Elsevier B.V. All rights reserved.