Using a material database and data fusion method to accelerate the process model development of high shear wet granulation

High shear wet granulation (HSWG) has been wildly used in manufacturing of oral solid dosage (OSD) forms, and process modeling is vital to understanding and controlling this complex process. In this paper, data fusion and multivariate modeling technique were applied to develop a formulation-process-quality model for HSWG process. The HSWG experimental data from both literature and the authors’ laboratory were fused into a single and formatted representation.

A material database and material matching method were used to compensate the incomplete physical characterization of literature formulation materials, and dimensionless parameters were utilized to reconstruct process variables at different granulator scales. The exploratory study on input materials properties by principal component analysis (PCA) revealed that the formulation data collected from different articles generated a formulation library which was full of diversity. In prediction of the median granule size, the partial least squares (PLS) regression models derived from literature data only and a combination of literature data and laboratory data were compared.

The results demonstrated that incorporating a small number of laboratory data into the multivariate calibration model could help significantly reduce the prediction error, especially at low level of liquid to solid ratio. The proposed data fusion methodology was beneficial to scientific development of HSWG formulation and process, with potential advantages of saving both experimental time and cost.

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Article information: Wang, Z., Cao, J., Li, W. et al. Using a material database and data fusion method to accelerate the process model development of high shear wet granulation. Sci Rep 11, 16514 (2021). https://doi.org/10.1038/s41598-021-96097-x

Materials

In the formulation matrix mentioned in “Formulation properties estimation” section, there involved 3 kinds of HPMC, 6 kinds of lactose and 5 kinds of MCC, which were top three frequently used materials. Therefore, two cellulose materials and four lactose materials were selected from the iTCM material library to generate the simulated and experimental formulations. Microcrystalline cellulose (MCC) PH101 (lot No. 1545) was purchased from Asahi Kasei Chemicals Co., Ltd. (Japan). Lactose monohydrate Pharmatose^® 110M (Batch No. 1009CON), Pharmatose^® 200M (Batch No. 10095MW), Anhydrous lactose 21AN (Batch No. 1007NX8) and HPMC E15LV (Batch No. D011F6KL01) were purchased from Shanghai Chineway Pharmaceutical Technology Co., Ltd. (Shanghai, China). Lactose granulac^® 200 (lot No. L1535) was purchased from Molkerei MEGGLE Wasserburg GmbH&Co. KG. (Germany). The deionized water was used as the granulation liquid.