Tags

Type your tag names separated by a space and hit enter

Managing API raw material variability during continuous twin-screw wet granulation.
Int J Pharm. 2019 Apr 20; 561:265-273.IJ

Abstract

Very few studies have investigated the impact of raw material variability upon the granule critical quality attributes (CQAs) produced via twin-screw wet granulation (i.e., granule size distribution, density, flowability). In this study, the impact of the raw material variability of an active pharmaceutical ingredient (API) in a high dose formulation on the twin-screw wet granulation process and on the resulting granule quality attributes was investigated. In a previous study (Stauffer et al., 2018), eight API batches were characterized to determine the API batch-to-batch variability. Principal component analysis (PCA) was then used to analyse the raw material property differences between the API batches and to determine the causes of the batch-to-batch variability. In current study, the three principal components from that PCA model were used as factors together with twin-screw granulation process parameters (i.e., screw speed and liquid-to-solid ratio) in a D-optimal screening design of experiments to understand the influence of these factors upon the granule CQAs. It was found that the API particle size distribution and related properties (e.g., density, agglomeration profile) were critical for the granule CQAs. In a next step, the significant factors from the screening design results were used to determine the design space of the twin-screw granulation process for the studied formulation via a D-optimal optimisation design, herewith controlling the risk of failure for the potential API raw material variability. The possibility to obtain suitable granule CQAs with a risk of failure of 1% for all API batches was demonstrated. It was thus possible to identify a combination of process parameters that can manage the API batch-to-batch variability leading to granules with pre-defined suitable CQAs.

Authors+Show Affiliations

Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Drug Delivery Design and Development, UCB, Braine l'Alleud, Belgium.Drug Delivery Design and Development, UCB, Braine l'Alleud, Belgium.Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium. Electronic address: thomas.debeer@ugent.be.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30851387

Citation

Stauffer, F, et al. "Managing API Raw Material Variability During Continuous Twin-screw Wet Granulation." International Journal of Pharmaceutics, vol. 561, 2019, pp. 265-273.
Stauffer F, Vanhoorne V, Pilcer G, et al. Managing API raw material variability during continuous twin-screw wet granulation. Int J Pharm. 2019;561:265-273.
Stauffer, F., Vanhoorne, V., Pilcer, G., Chavez, P. F., Vervaet, C., & De Beer, T. (2019). Managing API raw material variability during continuous twin-screw wet granulation. International Journal of Pharmaceutics, 561, 265-273. https://doi.org/10.1016/j.ijpharm.2019.03.012
Stauffer F, et al. Managing API Raw Material Variability During Continuous Twin-screw Wet Granulation. Int J Pharm. 2019 Apr 20;561:265-273. PubMed PMID: 30851387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Managing API raw material variability during continuous twin-screw wet granulation. AU - Stauffer,F, AU - Vanhoorne,V, AU - Pilcer,G, AU - Chavez,Pierre-François, AU - Vervaet,C, AU - De Beer,T, Y1 - 2019/03/06/ PY - 2019/01/11/received PY - 2019/03/04/revised PY - 2019/03/05/accepted PY - 2019/3/10/pubmed PY - 2019/8/20/medline PY - 2019/3/10/entrez KW - Continuous manufacturing KW - Managing active pharmaceutical ingredient variability KW - Material properties KW - Multivariate data analysis KW - Quality by design KW - Twin-screw granulation SP - 265 EP - 273 JF - International journal of pharmaceutics JO - Int J Pharm VL - 561 N2 - Very few studies have investigated the impact of raw material variability upon the granule critical quality attributes (CQAs) produced via twin-screw wet granulation (i.e., granule size distribution, density, flowability). In this study, the impact of the raw material variability of an active pharmaceutical ingredient (API) in a high dose formulation on the twin-screw wet granulation process and on the resulting granule quality attributes was investigated. In a previous study (Stauffer et al., 2018), eight API batches were characterized to determine the API batch-to-batch variability. Principal component analysis (PCA) was then used to analyse the raw material property differences between the API batches and to determine the causes of the batch-to-batch variability. In current study, the three principal components from that PCA model were used as factors together with twin-screw granulation process parameters (i.e., screw speed and liquid-to-solid ratio) in a D-optimal screening design of experiments to understand the influence of these factors upon the granule CQAs. It was found that the API particle size distribution and related properties (e.g., density, agglomeration profile) were critical for the granule CQAs. In a next step, the significant factors from the screening design results were used to determine the design space of the twin-screw granulation process for the studied formulation via a D-optimal optimisation design, herewith controlling the risk of failure for the potential API raw material variability. The possibility to obtain suitable granule CQAs with a risk of failure of 1% for all API batches was demonstrated. It was thus possible to identify a combination of process parameters that can manage the API batch-to-batch variability leading to granules with pre-defined suitable CQAs. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/30851387/Managing_API_raw_material_variability_during_continuous_twin_screw_wet_granulation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(19)30190-5 DB - PRIME DP - Unbound Medicine ER -