Using a Material Library to Understand the Change of Tabletability by High Shear Wet Granulation

Understanding the tabletability change of materials after granulation is critical for the formulation and process design in tablet development. In this paper, a material library consisting of 30 pharmaceutical materials was used to summarize the pattern of change of tabletability during high shear wet granulation and tableting (HSWGT). Each powdered material and the corresponding granules were characterized by 19 physical properties and nine compression behavior classification system (CBCS) parameters. Principal component analysis (PCA) was used to compare the physical properties and compression behaviors of ungranulated powders and granules. A new index, namely the relative change of tabletability (CoT_r), was proposed to quantify the tabletability change, and its advantages over the reworking potential were demonstrated.

On the basis of CoT_r values, the tabletability change classification system (TCCS) was established. It was found that approximately 40% of materials in the material library presented a loss of tabletability (i.e., Type I), 50% of materials had nearly unchanged tabletability (i.e., Type II), and 10% of materials suffered from increased tabletability (i.e., Type III). With the help of tensile strength (TS) vs. compression pressure curves implemented on both powders and granules, a data fusion method and the PLS2 algorithm were further applied to identify the differences in material properties requirements for direct compression (DC) and HSWGT. Results indicated that increasing the plasticity or porosity of the starting materials was beneficial to acquiring high TS of tablets made by HSWGT.

In conclusion, the presented TCCS provided a means for the initial risk assessment of materials in tablet formulation design and the data modeling method helped to predict the impact of formulation ingredients on the strength of compacts.

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Materials

To establish the material library 30 materials including 18 pharmaceutical excipients and 12 natural product powders (NPPs) were used. All pharmaceutical excipients were purchased commercially, and these excipients played the roles of diluents, binders, and disintegrants in tablet formulations. The selected excipients were suitable for direct compression and/or granulation processes. According to the deformation characteristics of materials, the excipients could be divided into three types, i.e., the plastic, the brittle, and the elastic. Microcrystalline cellulose PH101 (MCC PH101) and silicified microcrystalline cellulose (SMCC) were typical plastic excipients [51]. The brittle excipients included mannitol, calcium phosphate (CaP), dibasic calcium phosphate (DCP), dibasic calcium phosphate anhydrous (DCPA), lactose granulac 200 (Lac G200), and lactose flowlac 100 (Lac F100) [52,53,54].

The elastic excipients contained pregelatinized starch (PGS), soluble starch, and dextrin [55,56,57]. Among these excipients, SMCC and lactose cellactose 80 (Lac C80) were co-processed excipients. All NPPs were provided by the Beijing Tcmages Pharmaceutical Co., Ltd. (Beijing, China) and were prepared from 12 medicinal plant that involved commonly used medicinal parts, e.g., roots, rhizomes, bark, fruits, flowers, and aerial parts. The manufacturing processes of each NPP included a series of unit operations, such as pretreatment, extraction, filtration, concentration, and spray drying. Compared to excipients, NPPs had the characteristics of multiple compositions, high hygroscopicity, low glass transition temperatures, poor flowability, and compactability [58]. NPPs were chosen in expectation of enriching the diversity of the material library.

Wang, Y.; Cao, J.; Zhao, X.; Liang, Z.; Qiao, Y.; Luo, G.; Xu, B. Using a Material Library to Understand the Change of Tabletability by High Shear Wet Granulation. Pharmaceutics 2022, 14, 2631. https://doi.org/10.3390/pharmaceutics14122631