The development and validation of a quality by design based process analytical tool for the inline quantification of Ramipril during hot-melt extrusion

Abstract

The development and validation of a quality by design based process analytical tool for the inline quantification of Ramipril during hot-melt extrusion

The optimization of process analytical technology for the inline quantification of multiple drugs in fixed dose combinations during continuous processing

“…In our previous work, we confirmed the feasibility of utilising HME as a continuous processing platform for the manufacture of FDCs for the management of chronic diseases (Andrews et al, 2019b;Kelleher et al, 2018). Additionally, we demonstrated the suitability of Raman spectroscopy for the inline quantification of Ramipril during processing by utilising the quality by design approach and PAT framework (Andrews et al, 2019a;Dadou et al, 2020b).…”

“…Nevertheless, HME has not been widely implemented as a means of routine oral dose manufacture in the pharmaceutical industry. Major challenges include regulatory uncertainty towards such manufacturing platforms, and the need to reconsider the infrastructure of companies to accommodate the emerging view of advanced manufacturing technologies (Dadou et al, 2020b;Lee, 2017).…”

“…Implementing PAT to the production line enables the real-time release testing of materials during manufacturing by employing non-destructive technologies (Dadou et al, 2020b;Hisada et al, 2020). Thus, the quality of formulations and/or processes can be controlled during pharmaceutical process, such as drug quantification, water content and monitoring the solidstate of drugs (Koide et al, 2020;Nomura et al, 2020).…”

The design and development of high drug loading amorphous solid dispersion for hot-melt extrusion platform

“…This field of cross-disciplinary research between advanced therapeutics, computational tools and manufacturing technologies under the umbrella of QbD based digital frameworks will ultimately transform the amorphous formulation design and process into a new field of predictive science. Subsequently, we believe that the specific knowledge and expertise will be combined to develop reliable amorphous formulation and process design tools for quality and rapid realisation of advanced therapies in the foreseeable future (Dadou et al, 2020). Therefore, the development of digital framework based on both thermodynamic and kinetic principles for drugpolymer combinations integrated with specific manufacturing techniques will be vital for this industry.…”

Towards predicting the product quality in hot-melt extrusion: Small scale extrusion

“…Hot melt extrusion (HME) is increasingly applied in the pharmaceutical industry, mostly for solubilization of poorly soluble active pharmaceutical ingredients ( McFall et al 2019 ; Monschke et al 2020 ; Schittny et al 2018 ; Steffens and Wagner 2020 ; Vasoya et al 2019 ) (APIs) in immediate release, control release ( Fukuda et al 2006 ; Vo et al 2016 ; Zhu et al 2006 ) and nano ( Baumgartner et al, 2016 , Baumgartner et al, 2014 ; Bhagurkar et al 2017 ; Patil et al 2015 ; Silva et al 2018 ) formulations, as well as for the manufacturing of specific drug delivery devices ( Bode et al 2019 ; Cossé et al 2017 ; Eder et al 2017 ; Koutsamanis et al 2019 ). This trend calls for fast, reliable and inexpensive product and process development ( Breitenbach 2002 ; Crowley et al 2007 ; Dadou et al 2020 ; Evans et al 2018 ; Huang et al 2017 ; Kohlgrüber 2007 ; Matić et al 2020 ; Patil et al 2016 ; Rauwendaal 2014 ; Repka et al 2007 ; Saerens et al 2013 ). Typically, formulation and process development are disconnected, i.e., during the formulation development the formulation's processability is not considered.…”