api polymer pharma

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Aman ImaniMacalester College

CHEM 394: Polymer and Macromolecular Chemistry

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The players

• Active pharmaceutical ingredient/s (API)

• Binder (e.g. PVP, starch, cellulose)

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The game

• Interaction of API and binders– API: acetaminophen (ACM); Sulfamerazine (SMZ)

– Binders: Hydroxypropylcellulose (HPC); Polyvinylpyrrolidone (PVP)

• Tabletability–Wet granulation• Improved compaction + flow behavior• Overgranulation

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Why interfaces b/w powders and polymers?

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The referees

• Ellipsometry: measures change in polarization of light after reflection and refraction from a film

– VASE (variable angle spectroscopic ellipsometer)

• Neutron Reflectometry:– Neutrons directed onto sample at low angle– Time-of-flight measured– Reflectivity as a fn.

• Intensity of incident beam: intensity of reflected beam

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Sample preparation

API film

Conc. Polymer

soln

Solvent

Solvent

Polymer-bound

API

impell

er

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Ellipsometer

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Ellipsometer

• Useful for dividing the simulated API composites into 3 categories:– No API-binder interaction (SMZ-PVP)– Some API-binder interaction (SMZ-HPC, ACM-HPC)– Definite API-binder interaction (ACM-PVP)

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Neutron Reflectometer

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Neutron Reflectometry

• Scattering Length Density (SLD) is a fn. of chemical composition and density

• SLD modeled as fn. of depth into sample to provide high definition of the intermixing regions for each category

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Results

• Ellipsometry

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Results• Neutron Reflectometry

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References• Yeager, John D., Kyle J. Ramos, Changquan C. Sun, Saurabh Singh,

Manish Dubey, Jaroslaw Majewski, and Daniel E. Hooks. "Probing Interfaces between Pharmaceutical Crystals and Polymers by Neutron Reflectometry." Molecular Pharmaceutics 9.7 (2012): 1953-961

• "Ellipsometry." Wikipedia. Wikimedia Foundation• James, Michael. "Report on Neutron Reflectometry." (2001)

Australian Research Reactor• Berk, N. F., and C. F. Majkrzak. "Analysis of Multibeam Data for

Neutron Reflectivity." Langmuir 25.7 (2009): 4145-153

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Reference FiguresDip coating