Improving powder flow properties of a direct compression formulation using a two-step glidant mixing process.

ABSTRACT

To improve powder flow of a high-dose direct compression formulation (drug content 30%), we compared a two-step operation for mixing glidants with a conventional one-step glidant mixing process. This two-step mixing operation was studied with two kinds of mixtures; an active pharmaceutical ingredient (API)-glidant combination and a direct compression excipient-glidant combination. The two-step operation permitted the selection of the optimum glidant type and concentration in each glidant-mixing procedure even though the formulation had different powder properties such as micronized API and enlarged direct compression vehicles, whereas the conventional approaches forced the selection of a certain glidant type and concentration at one-step mixing. The addition of 0.5% nonporous silica markedly improved API flow. In contrast, 1.0% porous silica was the appropriate glidant to enhance excipient flow at direct compression excipient-glidant mixing. The two-step operation dominantly enhanced powder flow when the appropriate API-glidant mixture and the suitable direct compression excipients-glidant mixture were blended compared to the one-step operation with its optimum glidant concentration. The results showed that the angle of repose was 43 degrees and the critical orifice diameter was 10 mm in the two-step operation, whereas it was 47 degrees and 16 mm in the one-step operation. The two-step operation of glidant mixing enhanced powder flow of the high-dose direct compression formulation compared with the one-step operation. The two-step operation eliminates the bottleneck of powder flow and allows direct compression to be more worth applying for formulation and process development trials.