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Simplified end-to-end continuous manufacturing by feeding API suspensions in twin-screw wet granulation.
Eur J Pharm Biopharm. 2018 Dec; 133:224-231.EJ

Abstract

This study focussed on investigating the coupling of continuous manufacturing of drug substance and continuous manufacture of drug product. An important step in such an integrated end-to-end continuous manufacturing was envisioned by dosing the API as suspension into a twin-screw wet granulation process. To achieve this goal, a model drug substance (ibuprofen) was fed as a concentrated aqueous suspension (50% w/w) into a twin-screw granulator and compared against traditional solid feeding of the model drug substance to meet a target ibuprofen load of 60% w/w in the formulation. Granulation and compaction behaviour were evaluated to determine the impact of feeding API as suspension in twin-screw wet granulation on the critical quality attributes of the drug product. It was demonstrated that the ibuprofen suspension feed is comparable with the ibuprofen dry blend feed in twin-screw wet granulation. Next to enabling end-to-end continuous manufacturing, API suspension feed in twin-screw wet granulation could afford a number of additional advantages including manufacturing efficiency by removing the drying step for API, or overcoming processing issues linked to the bulk properties of the API powder (e.g. flowability).

Authors+Show Affiliations

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, 40225 Duesseldorf, Germany; Novartis AG, Novartis Campus, 4002 Basel, Switzerland.Novartis AG, Novartis Campus, 4002 Basel, Switzerland.Novartis AG, Novartis Campus, 4002 Basel, Switzerland.Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, 40225 Duesseldorf, Germany.Novartis AG, Novartis Campus, 4002 Basel, Switzerland. Electronic address: Markus.Krumme@novartis.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30291963

Citation

Schmidt, Adrian, et al. "Simplified End-to-end Continuous Manufacturing By Feeding API Suspensions in Twin-screw Wet Granulation." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 133, 2018, pp. 224-231.
Schmidt A, de Waard H, Moll KP, et al. Simplified end-to-end continuous manufacturing by feeding API suspensions in twin-screw wet granulation. Eur J Pharm Biopharm. 2018;133:224-231.
Schmidt, A., de Waard, H., Moll, K. P., Kleinebudde, P., & Krumme, M. (2018). Simplified end-to-end continuous manufacturing by feeding API suspensions in twin-screw wet granulation. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 133, 224-231. https://doi.org/10.1016/j.ejpb.2018.09.026
Schmidt A, et al. Simplified End-to-end Continuous Manufacturing By Feeding API Suspensions in Twin-screw Wet Granulation. Eur J Pharm Biopharm. 2018;133:224-231. PubMed PMID: 30291963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simplified end-to-end continuous manufacturing by feeding API suspensions in twin-screw wet granulation. AU - Schmidt,Adrian, AU - de Waard,Hans, AU - Moll,Klaus-Peter, AU - Kleinebudde,Peter, AU - Krumme,Markus, Y1 - 2018/10/04/ PY - 2018/02/03/received PY - 2018/09/25/revised PY - 2018/09/25/accepted PY - 2018/10/7/pubmed PY - 2019/3/5/medline PY - 2018/10/7/entrez KW - Agglomeration KW - Compaction KW - Continuous pharmaceutical manufacturing KW - Formulation KW - Granule and tablet quality KW - Paste KW - Water content SP - 224 EP - 231 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 133 N2 - This study focussed on investigating the coupling of continuous manufacturing of drug substance and continuous manufacture of drug product. An important step in such an integrated end-to-end continuous manufacturing was envisioned by dosing the API as suspension into a twin-screw wet granulation process. To achieve this goal, a model drug substance (ibuprofen) was fed as a concentrated aqueous suspension (50% w/w) into a twin-screw granulator and compared against traditional solid feeding of the model drug substance to meet a target ibuprofen load of 60% w/w in the formulation. Granulation and compaction behaviour were evaluated to determine the impact of feeding API as suspension in twin-screw wet granulation on the critical quality attributes of the drug product. It was demonstrated that the ibuprofen suspension feed is comparable with the ibuprofen dry blend feed in twin-screw wet granulation. Next to enabling end-to-end continuous manufacturing, API suspension feed in twin-screw wet granulation could afford a number of additional advantages including manufacturing efficiency by removing the drying step for API, or overcoming processing issues linked to the bulk properties of the API powder (e.g. flowability). SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/30291963/Simplified_end_to_end_continuous_manufacturing_by_feeding_API_suspensions_in_twin_screw_wet_granulation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(18)30020-1 DB - PRIME DP - Unbound Medicine ER -