Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec 5;11(12):654.
doi: 10.3390/pharmaceutics11120654.

Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance

Edina Szabó  1 , Balázs Démuth  1 , Dorián László Galata  1 , Panna Vass  1 , Edit Hirsch  1 , István Csontos  1 , György Marosi  1 , Zsombor K Nagy  1
Affiliations
Review

Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance

Edina Szabó et al. Pharmaceutics. .

Abstract

Preparation and formulation of amorphous solid dispersions (ASDs) are becoming more and more popular in the pharmaceutical field because the dissolution of poorly water-soluble drugs can be effectively improved this way, which can lead to increased bioavailability in many cases. During downstream processing of ASDs, technologists need to keep in mind both traditional challenges and the newest trends. In the last decade, the pharmaceutical industry began to display considerable interest in continuous processing, which can be explained with their potential advantages such as smaller footprint, easier scale-up, and more consistent product, better quality and quality assurance. Continuous downstream processing of drug-loaded ASDs opens new ways for automatic operation. Therefore, the formulation of poorly water-soluble drugs may be more effective and safe. However, developments can be challenging due to the poor flowability and feeding properties of ASDs. Consequently, this review pays special attention to these characteristics since the feeding of the components greatly influences the content uniformity in the final dosage form. The main purpose of this paper is to summarize the most important steps of the possible ASD-based continuous downstream processes in order to give a clear overview of current course lines and future perspectives.

Keywords: amorphous solid dispersions; continuous manufacturing; feeding; formulation; powder characterization.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Advantages of drug-loaded polymer-based amorphous solid dispersions (ASDs).
Figure 2
Figure 2
Schematic design of a possible electrospinning-based continuous formulation system [70].
Figure 3
Figure 3
Flowchart of possible continuous pharmaceutical manufacturing routes for preparing ASD-loaded tablets.
Figure 4
Figure 4
Main influencing factors of polymer-based ASDs’ flowability.
Figure 5
Figure 5
Effects of process parameters on the particle size of the product (red bold labels indicate the influencing factors.).
Figure 6
Figure 6
Schematic design of a possible loss-in-weight feeder setup with different operation modes.
See this image and copyright information in PMC

References

    1. Lipinski C.A., Lombardo F., Dominy B.W., Feeney P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 2012;64:4–17. doi: 10.1016/j.addr.2012.09.019. - DOI - PubMed
    1. Pouton C.W. Formulation of poorly water-soluble drugs for oral administration: Physicochemical and physiological issues and the lipid formulation classification system. Eur. J. Pharm. Sci. 2006;29:278–287. doi: 10.1016/j.ejps.2006.04.016. - DOI - PubMed
    1. Kawabata Y., Wada K., Nakatani M., Yamada S., Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int. J. Pharm. 2011;420:1–10. doi: 10.1016/j.ijpharm.2011.08.032. - DOI - PubMed
    1. Vasconcelos T., Sarmento B., Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov. Today. 2007;12:1068–1075. doi: 10.1016/j.drudis.2007.09.005. - DOI - PubMed
    1. Borbás E., Sinkó B.L., Tsinman O., Tsinman K., Kiserdei E.V., Démuth B.Z., Balogh A., Bodák B., Domokos A.S., Dargó G. Investigation and mathematical description of the real driving force of passive transport of drug molecules from supersaturated solutions. Mol. Pharm. 2016;13:3816–3826. doi: 10.1021/acs.molpharmaceut.6b00613. - DOI - PubMed

LinkOut - more resources