The material library is an emerging, new data-driven approach for developing pharmaceutical process models. How many materials or samples should be involved in a particular application scenario is unclear, and the impact of sample size on process modeling is worth discussing. In this work, the direct compression process was taken as the research object, and the effects of different sample sizes of material libraries on partial least squares (PLS) modeling in the prediction of tablet tensile strength were investigated. A primary material library comprising 45 materials was built. Then, material subsets containing 5 × i (i = 1, 2, 3, …, 8) materials were sampled from the primary material library. Each subset underwent sampling 1000 times to analyze variations in model fitting performance. Both hierarchical sampling and random sampling were employed and compared, with hierarchical sampling implemented with the help of the tabletability classification index d. For each subset, modeling data were organized, incorporating 18 physical properties and tableting pressure as the independent variables and tablet tensile strength as the dependent variable. A series of chemometric indicators was used to assess model performance and find important materials for model training. It was found that the minimum R2 and RMSE values reached their maximum, and the corresponding values were kept almost unchanged when the sample sizes varied from 20 to 45. When the sample size was smaller than 15, the hierarchical sampling method was more reliable in avoiding low-quality few-shot PLS models than the random sampling method. Two important materials were identified as useful for building an initial material library. Overall, this work demonstrated that as the number of materials increased, the model's reliability improved. It also highlighted the potential for effective few-shot modeling on a small material library by controlling its information richness.

The purpose of this study is to use a material library to investigate the effect of raw material properties on ribbon tensile strength (TS) and solid fraction (SF) in the roll compaction (RC) process. A total of 81 pharmaceutical materials, including 53 excipients and 28 natural product powders (NPPs), were characterized by 22 material descriptors and were compacted under five different hydraulic pressures. The transversal and longitudinal splitting behaviors of the ribbons were summarized. The TS-porosity and TS-pressure relationships were used to explain the roll compaction behavior of powdered materials. Through defining the target ribbon quality (i.e., 0.6 ≤ SF ≤ 0.8 and TS ≥ 1 MPa), the roll compaction behavior classification system (RCBCS) was built and 81 materials were classified into three categories. A total of 24 excipients and five NPPs were classified as Category I materials, which fulfilled the target ribbon quality and had less occurrence of transversal splitting. Moreover, the multivariate relationships between raw material descriptors, the hydraulic pressure and ribbon quality attributes were obtained by PLS regression. Four density-related material descriptors and the cohesion index were identified as critical material attributes (CMAs). The multi-objective design space summarizing the feasible material properties and operational region for the RC process were visualized. The RCBCS presented in this paper enables a formulator to perform the initial risk assessment of any new materials, and the data modeling method helps to predict the impact of formulation ingredients on strength and porosity of compacts.

An efficient delivery system is critical for the success of cell therapy. To deliver cells to a dynamic organ, the biomaterial vehicle should mechanically match with the non-linearly elastic host tissue. In this study, non-linearly elastic biomaterials have been fabricated from a chemically crosslinked elastomeric poly(glycerol sebacate) (PGS) and thermoplastic poly(l-lactic acid) (PLLA) using the core/shell electrospinning technique. The spun fibrous materials containing a PGS core and PLLA shell demonstrate J-shaped stress-strain curves, having ultimate tensile strength (UTS), rupture elongation and stiffness constants of 1 ± 0.2 MPa, 25 ± 3% and 12 ± 2, respectively, which are comparable to skin tissue properties reported previously. Our ex vivo and in vivo trials have shown that the elastomeric mesh supports and fosters the growth of enteric neural crest (ENC) progenitor cells, and that the cell-seeded elastomeric fibrous sheet physically remains in intimate contact with guts after grafting, providing the effective delivery of the progenitor cells to an embryonic and post-natal gut environment.

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 (CoTr), was proposed to quantify the tabletability change, and its advantages over the reworking potential were demonstrated. On the basis of CoTr 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.