Characterization of Powder- and Tablet Properties of Different Direct Compaction Grades of Mannitol Using a Kohonen Self-organizing Map and a Lasso Regression Model

Atsushi Kosugi, Kok Hoong Leong, Hinako Tsuji, Yoshihiro Hayashi, Shungo Kumada, Kotaro Okada, Yoshinori Onuki

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)

    Abstract

    The purpose of this study was to accumulate enhanced technical knowledge about the powder properties of direct compaction grades of mannitol that could lead to new tablet formulations. Fifteen different commercial direct compaction grades of mannitol were tested. Ten different powder properties representing flowability, particle size, specific surface area and manufacturing properties were measured. In addition, model tablets of each mannitol grade were prepared, and their disintegration time, friability, and tensile strength were measured. The data were analyzed by principle component analysis and a Kohonen self-organizing map to find correlations between powder properties. Self-organizing map clustering successfully classified the test grades into 5 distinct clusters having different powder properties. Each cluster was well characterized by statistical profiling. Subsequently, the contribution of the powder properties to the tablet properties was investigated by a least absolute shrinkage- and selection operator (Lasso) regression model. Mannitol grades with a larger particle size (D90) were prone to produce tablets with longer disintegration time, while a larger specific surface area of the particles was positively associated with tablets with higher mechanical strength. Our findings provide valuable information for the design of tablet formulations.

    Original languageEnglish
    Pages (from-to)2585-2593
    Number of pages9
    JournalJournal of Pharmaceutical Sciences
    Volume109
    Issue number8
    DOIs
    Publication statusPublished - Aug 2020

    All Science Journal Classification (ASJC) codes

    • Pharmaceutical Science

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