Investigation of dissolution rate kinetics of bulk pharmaceutical feed streams within a stirred tank vessel and a twin screw extruder

Abstract

The introduction of continuous manufacturing of pharmaceuticals has highlighted the challenging area of continuous dissolution of solids for work ups to flow chemistry systems. In this study, the use of a 16 mm twin screw extruder (TSE) as a platform technology for solid feeds is investigated using four solid pharmaceutical ingredients (PI) in a mixture of water and IPA. In order for comparison, the same experiments were also carried out in a batch traditional stirred tank vessel (STV). The objectives of this work are to gain further scientific understanding on dissolution kinetics and to compare kinetics in both a batch and continuous system. The concentration of each PI during dissolution is monitored using an in-line UV-ATR probe, allowing the extraction of dissolution kinetics. Faster dissolution rates are achieved in the TSE than in the STV due to higher power dissipation generated by the aggressive shear mixing and thermal energy within the TSE. Complete dissolution of paracetamol is obtained within the residence time of the TSE; complete dissolution of benzoic acid and acetylsalicylic acid are achieved at higher barrel temperatures; however full dissolution of nicotinic acid is not achievable in the TSE under the experimental conditions.

Graphical Abstract

Keywords:

• Dissolution
• solid dosing
• kinetics
• continuous pharmaceutical manufacture
• twin screw extruder
• UV spectrometry

Acknowledgments

The authors thank EPSRC, the Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, and GSK for their support and funding. Particular thanks and acknowledgement go to the mentoring support provided by Gareth Alford, GSK. The authors acknowledge that this work was carried out in the CMAC National Facility, housed within the University of Strathclyde’s Technology and Innovation Centre, and funded with a UKRPIF (UK Research Partnership Institute Fund) capital award from the Higher Education Funding Council for England (HEFCE).

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by Engineering and Physical Sciences Research Council [EP/K503289/1]; UKRPIF (UK Research Partnership Institute Fund) capital award, under Grant SFC ref. H13054, from the Higher Education Funding Council for England (HEFCE); and GlaxoSmithKline Pharmaceuticals.