Understanding the role of magnesium stearate in lowering punch sticking propensity of drugs during compression

Chamara Gunawardana; Angela Kong; Debbie Wanapun; Daniel O. Blackwood; C. Travis Powell; Joseph F. Krzyzaniak; Myles C. Thomas; John E. Kresevic; Changquan Calvin Sun

doi:10.1016/j.ijpharm.2023.123016

Understanding the role of magnesium stearate in lowering punch sticking propensity of drugs during compression

Chamara Gunawardana, Angela Kong, Debbie Wanapun, Daniel O. Blackwood, C. Travis Powell, Joseph F. Krzyzaniak, Myles C. Thomas, John E. Kresevic, Changquan Calvin Sun

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

The sticking of active pharmaceutical ingredient (API) to the surfaces of compaction tooling, frequently referred to as punch sticking, causes costly downtime or product failures in commercial tablet manufacturing. Magnesium stearate (MgSt) is a common tablet lubricant known to ameliorate the sticking problem, even though there exist exceptions. The mechanism by which MgSt lowers punch sticking propensity (PSP) by covering API surface is sensible but not yet experimentally proven. This work was aimed at elucidating the link between PSP and surface area coverage (SAC) of tablets by MgSt, in relation to some key formulation properties and process parameters, namely MgSt concentration, API loading, API particle size, and mixing conditions. The study was conducted using two model APIs with known high PSPs, tafamidis (TAF) and ertugliflozin-pyroglutamic acid (ERT). Results showed that PSP decreases exponentially with increasing SAC by MgSt. The composition of material stuck to punch face was also explored to better understand the onset of punch sticking and the impact of possible MgSt-effected punch conditioning event.

Original language	English (US)
Article number	123016
Pages (from-to)	123016
Journal	International journal of pharmaceutics
Volume	640
DOIs	https://doi.org/10.1016/j.ijpharm.2023.123016 https://doi.org/10.1016/j.ijpharm.2023.123016
State	Published - Jun 10 2023

Bibliographical note

Funding Information:
Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. CCS thanks the National Science Foundation for support through the Industry University Collaborative Research Center grant IIP-2137264, Center for Integrated Materials Science and Engineering for Pharmaceutical Products (CIMSEPP).

Publisher Copyright:
© 2023 Elsevier B.V.

Keywords

Magnesium stearate
Punch conditioning
Punch sticking propensity
Surface area coverage
Tablet formulation

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Gunawardana, C., Kong, A., Wanapun, D., Blackwood, D. O., Travis Powell, C., Krzyzaniak, J. F., Thomas, M. C., Kresevic, J. E., & Sun, C. C. (2023). Understanding the role of magnesium stearate in lowering punch sticking propensity of drugs during compression. International journal of pharmaceutics, 640, 123016. Article 123016. https://doi.org/10.1016/j.ijpharm.2023.123016, https://doi.org/10.1016/j.ijpharm.2023.123016

Gunawardana, C, Kong, A, Wanapun, D, Blackwood, DO, Travis Powell, C, Krzyzaniak, JF, Thomas, MC, Kresevic, JE & Sun, CC 2023, 'Understanding the role of magnesium stearate in lowering punch sticking propensity of drugs during compression', International journal of pharmaceutics, vol. 640, 123016, pp. 123016. https://doi.org/10.1016/j.ijpharm.2023.123016, https://doi.org/10.1016/j.ijpharm.2023.123016

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title = "Understanding the role of magnesium stearate in lowering punch sticking propensity of drugs during compression",

abstract = "The sticking of active pharmaceutical ingredient (API) to the surfaces of compaction tooling, frequently referred to as punch sticking, causes costly downtime or product failures in commercial tablet manufacturing. Magnesium stearate (MgSt) is a common tablet lubricant known to ameliorate the sticking problem, even though there exist exceptions. The mechanism by which MgSt lowers punch sticking propensity (PSP) by covering API surface is sensible but not yet experimentally proven. This work was aimed at elucidating the link between PSP and surface area coverage (SAC) of tablets by MgSt, in relation to some key formulation properties and process parameters, namely MgSt concentration, API loading, API particle size, and mixing conditions. The study was conducted using two model APIs with known high PSPs, tafamidis (TAF) and ertugliflozin-pyroglutamic acid (ERT). Results showed that PSP decreases exponentially with increasing SAC by MgSt. The composition of material stuck to punch face was also explored to better understand the onset of punch sticking and the impact of possible MgSt-effected punch conditioning event.",

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author = "Chamara Gunawardana and Angela Kong and Debbie Wanapun and Blackwood, {Daniel O.} and {Travis Powell}, C. and Krzyzaniak, {Joseph F.} and Thomas, {Myles C.} and Kresevic, {John E.} and Sun, {Changquan Calvin}",

note = "Funding Information: Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. CCS thanks the National Science Foundation for support through the Industry University Collaborative Research Center grant IIP-2137264, Center for Integrated Materials Science and Engineering for Pharmaceutical Products (CIMSEPP). Publisher Copyright: {\textcopyright} 2023 Elsevier B.V.",

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AU - Kresevic, John E.

AU - Sun, Changquan Calvin

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N2 - The sticking of active pharmaceutical ingredient (API) to the surfaces of compaction tooling, frequently referred to as punch sticking, causes costly downtime or product failures in commercial tablet manufacturing. Magnesium stearate (MgSt) is a common tablet lubricant known to ameliorate the sticking problem, even though there exist exceptions. The mechanism by which MgSt lowers punch sticking propensity (PSP) by covering API surface is sensible but not yet experimentally proven. This work was aimed at elucidating the link between PSP and surface area coverage (SAC) of tablets by MgSt, in relation to some key formulation properties and process parameters, namely MgSt concentration, API loading, API particle size, and mixing conditions. The study was conducted using two model APIs with known high PSPs, tafamidis (TAF) and ertugliflozin-pyroglutamic acid (ERT). Results showed that PSP decreases exponentially with increasing SAC by MgSt. The composition of material stuck to punch face was also explored to better understand the onset of punch sticking and the impact of possible MgSt-effected punch conditioning event.

AB - The sticking of active pharmaceutical ingredient (API) to the surfaces of compaction tooling, frequently referred to as punch sticking, causes costly downtime or product failures in commercial tablet manufacturing. Magnesium stearate (MgSt) is a common tablet lubricant known to ameliorate the sticking problem, even though there exist exceptions. The mechanism by which MgSt lowers punch sticking propensity (PSP) by covering API surface is sensible but not yet experimentally proven. This work was aimed at elucidating the link between PSP and surface area coverage (SAC) of tablets by MgSt, in relation to some key formulation properties and process parameters, namely MgSt concentration, API loading, API particle size, and mixing conditions. The study was conducted using two model APIs with known high PSPs, tafamidis (TAF) and ertugliflozin-pyroglutamic acid (ERT). Results showed that PSP decreases exponentially with increasing SAC by MgSt. The composition of material stuck to punch face was also explored to better understand the onset of punch sticking and the impact of possible MgSt-effected punch conditioning event.

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Understanding the role of magnesium stearate in lowering punch sticking propensity of drugs during compression

Abstract

Bibliographical note

Keywords

MRSEC Support

PubMed: MeSH publication types

Publisher link

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University of Minnesota Materials Research Science and Engineering Center (DMR-2011401)

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Understanding the role of magnesium stearate in lowering punch sticking propensity of drugs during compression

Abstract

Bibliographical note

Keywords

MRSEC Support

PubMed: MeSH publication types

Publisher link

Find It

Other files and links

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University of Minnesota Materials Research Science and Engineering Center (DMR-2011401)

Cite this