End-to-end continuous manufacturing of conventional compressed tablets: From flow synthesis to tableting through integrated crystallization and filtration.
Int J Pharm
; 581: 119297, 2020 May 15.
Article
in En
| MEDLINE
| ID: mdl-32243964
ABSTRACT
An end-to-end continuous pharmaceutical manufacturing process was developed for the production of conventional direct compressed tablets on a proof-of-concept level for the first time. The output reaction mixture of the flow synthesis of acetylsalicylic acid was crystallized continuously in a mixed suspension mixed product removal crystallizer. The crystallizer was directly connected to a continuous filtration carousel device, thus the crystallization, filtration and drying of acetylsalicylic acid (ASA) was carried out in an integrated 2-step process. Steady state was reached during longer operations and the interaction of process parameters was evaluated in a series of experiments. The filtered crystals were ready for further processing in a following continuous blending and tableting experiment due to the good flowability of the material. The ASA collected during the crystallization-filtration experiments was fed into a continuous twin-screw blender along with microcrystalline cellulose as tableting excipient. After continuous blending Near-Infrared spectroscopy was applied to in-line analyze the drug content of the powder mixture. A belt conveyor carried the mixture towards an eccentric lab-scale tablet press, which continuously produced 500 mg ASA-loaded compressed tablets of 100 mg dose strength. Thus, starting from raw materials, the final drug product was obtained by continuous manufacturing steps with appropriate quality.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chemistry, Pharmaceutical
/
Aspirin
/
Compressive Strength
/
Crystallization
Language:
En
Journal:
Int J Pharm
Year:
2020
Type:
Article
Affiliation country:
United States