Dry pre-coating of active pharmaceutical ingredient with submicron-sized hydroxypropylcellulose in dry granulation using roller compactor improves granule properties

Abstract

We aimed to investigate the feasibility of our previously proposed method for improving the properties of dry granules by pre-coating of active pharmaceutical ingredients (API) with a submicron-sized binder before conventional roller compaction in bench-scale production. Hydroxypropylcellulose (HPC) and acetaminophen (APAP) were used as the binder and API with low compactibility, respectively. The submicron-sized HPC (HPC-subMP) was obtained using a bench-scale spray dryer; the weight fraction for particle size less than 1 μm was a maximum of approximately 50 wt%. Co-mixing APAP with 5–20 wt% HPC-subMP in the high shear mixer resulted in the APAP particles being pre-coated with HPC-subMP (HPC-coated APAP). The HPC-coated APAP particles were converted into granules following ribbons using roller compactors, mixed with other excipients and compressed as a formulation containing 50% APAP using a single-punch tableting machine. The tablets obtained showed a high tensile strength without significantly prolonged disintegration time; thus, the compactibility of the dry granules could be improved using the HPC-coated APAP. Raman imaging study suggested that the distributional homogeneity of HPC-subMP in the ribbons was an important factor in producing roller-compacted granules suitable for tableting of API with low compactibility without any fundamental changes in materials and manufacturing processes.