Prize Winner

Streaming Media

Type of Proposal

Oral presentation

Start Date

31-3-2017 9:00 AM

End Date

31-3-2017 10:20 AM

Faculty

Faculty of Science

Faculty Sponsor

Dr. Robert Schurko

Abstract

Over 50% of active pharmaceutical ingredients (APIs) are crystallized as simple salts, and of these, over 50% are HCI salts. In many instances, APIs can crystallize into pseudopolymorphic forms (e.g., hydrates or solvates), which have structures distinct from the non-hydrated or non-solvated solid phases. The polymorphic form of an API can influence such factors as the bioavailability, shelf life, toxicity, and solubility in the body. Additionally, each unique hydrate or solvate of an API represents unique intellectual property, and may be distinctly patented. As such, it is very important to precisely structurally characterize all solid forms of APIs. The focus of this project is to use 35CI SSNMR, pXRD, and quantum-chemical calculations to systematically study hydrates of HCI APIs. By analyzing the 35CI and 2H SSNMR spectra of different hydrated and anhydrous forms of various HCI salts, we hope to determine the nature by which water molecules directly and indirectly affect the molecular structures. First principles calculations of 35CI electric field gradient and chemical shielding tensors will aid in rationalizing symmetry/structure/spectral relationships. Preliminary studies on Cimetidine HCl monohydrate and Arginine HCl monohydrate have shown that quantum-chemical calculations do not accurately match experimental data for these hydrated systems. This may be due to dynamic motion of the water molecules in these compounds. By conducting 2H variable temperature SSNMR studies, it will be possible to address this specific hypothesis. It is our hope that these findings will be of interest to the pharmaceutical industry, for use in high throughput analysis of APIs, hydrate identification and detection of impurities, and disproportionation products.

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Mar 31st, 9:00 AM Mar 31st, 10:20 AM

A Study of Structure and Dynamics in Hydrated Active Pharmaceutical Ingredients

Over 50% of active pharmaceutical ingredients (APIs) are crystallized as simple salts, and of these, over 50% are HCI salts. In many instances, APIs can crystallize into pseudopolymorphic forms (e.g., hydrates or solvates), which have structures distinct from the non-hydrated or non-solvated solid phases. The polymorphic form of an API can influence such factors as the bioavailability, shelf life, toxicity, and solubility in the body. Additionally, each unique hydrate or solvate of an API represents unique intellectual property, and may be distinctly patented. As such, it is very important to precisely structurally characterize all solid forms of APIs. The focus of this project is to use 35CI SSNMR, pXRD, and quantum-chemical calculations to systematically study hydrates of HCI APIs. By analyzing the 35CI and 2H SSNMR spectra of different hydrated and anhydrous forms of various HCI salts, we hope to determine the nature by which water molecules directly and indirectly affect the molecular structures. First principles calculations of 35CI electric field gradient and chemical shielding tensors will aid in rationalizing symmetry/structure/spectral relationships. Preliminary studies on Cimetidine HCl monohydrate and Arginine HCl monohydrate have shown that quantum-chemical calculations do not accurately match experimental data for these hydrated systems. This may be due to dynamic motion of the water molecules in these compounds. By conducting 2H variable temperature SSNMR studies, it will be possible to address this specific hypothesis. It is our hope that these findings will be of interest to the pharmaceutical industry, for use in high throughput analysis of APIs, hydrate identification and detection of impurities, and disproportionation products.