Method of testing crystallinity in amorphous pharmaceutical compositions
AssigneeColvistec AG
InventorsAndreas Berghaus, Angela Spangenberg
Life of this patent
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Abstract
Methods of testing pharmaceutical compositions for the presence or absence of active pharmaceutical ingredient (API) crystallinity in an amorphous solid dispersion or solid-state solution using UV/vis spectrometry is provided. Testing may be performed standalone or during manufacturing of a pharmaceutical composition. A predictive model provides for quantitative analysis of the amount of crystalline API based on UV/vis data of corresponding reference samples. Also provided is an apparatus for manufacturing a pharmaceutical composition.
Claims16
A method of generating a predictive model for determining an amount of crystallinity of an active pharmaceutical ingredient (API) in an amorphous solid dispersion or solid-state solution, the method comprising:
- (i) subjecting a plurality of reference samples of dispersions or solutions spanning a range of API crystallinity to UV/vis spectroscopy using a UV/vis spectrometer;
- (ii) measuring a reflectance and/or transmission spectrum of each reference sample using the UV/vis spectrometer wherein the reflectance and/or transmission is produced from subjecting the plurality of reference samples to UV/vis spectroscopy according to step (i);
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- (iii) generating a predictive crystallinity model using principle component analysis (PCA) of the spectra from step (ii).
A method of testing a pharmaceutical composition comprising an active pharmaceutical ingredient (API) in an amorphous solid dispersion or solid-state solution for crystallinity of the API, the method comprising:
- (i) subjecting the pharmaceutical composition comprising the API in the amorphous solid dispersion or solid-state solution to UV/vis spectroscopy using a UV/vis spectrometer;
- (ii) measuring a reflectance and/or transmittance spectrum of the pharmaceutical composition comprising the API in the amorphous solid dispersion or solid-state solution using the UV/vis spectrometer wherein the reflectance and/or transmission is produced from subjecting the pharmaceutical composition to UV/vis spectroscopy according to step (i);
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- (iii) determining the presence or absence of crystallinity of the API of the pharmaceutical composition by comparing a measured reflectance and/or transmittance spectrum obtained from step (ii) to a reflectance and/or transmittance spectrum for a completely amorphous sample.
A method of manufacturing a pharmaceutical composition, comprising:
- (i) forming an active pharmaceutical ingredient (API) into an amorphous solid dispersion or solid state solution that comprises the API;
- (ii) testing the amorphous solid dispersion or solid-state solution for crystallinity of the API one or more times by
- (a) subjecting the amorphous solid dispersion or solid-state solution comprising the API to UV/vis spectroscopy using a UV/vis spectrometer;
- (b) measuring a reflectance and/or transmittance spectrum of the amorphous solid dispersion or solid-state solution comprising the API using the UV/vis spectrometer wherein the reflectance and/or transmission is produced from subjecting the amorphous solid dispersion or solid-state solution comprising the API to UV/vis spectroscopy according to step (a);
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- (c) determining the presence or absence of crystallinity of the API in the amorphous solid dispersion or solid-state solution by comparing a measured reflectance and/or transmittance spectrum obtained from step (b) to a reflectance and/or transmittance spectrum for a completely amorphous sample;
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- (iii) where the amorphous solid dispersion or solid-state solution has an amount of crystallinity within an acceptable range, processing the composition into a finished pharmaceutical product.
Dependencies are inferred from the claim text.