Development of quantification methods for crystalline polymorphs in pharmaceutical dosage form using low-frequency Raman spectroscopy

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18867
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: Inoue Motoki 明治薬科大学, 薬学部, 助教 (90722950)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Raman分光法 / 結晶多形 / 固形製剤

Outline of Final Research Achievements

The purpose of this study was to quantify polymorphs of active pharmaceutical ingredients in pharmaceutical tablets using low-frequency Raman spectroscopy. Low-frequency Raman spectroscopy can discriminate crystal polymorphs. It is well known that the quantification ability of transmission mode is high than that of backscattering mode. We therefore developed transmission low-frequency Raman spectroscopy and obtained novel transmission low-frequency Raman spectra. Carbamazepine form I and III were selected as model polymorphs, and prepared mixture of polymorphs as model tablets. The root-mean-square error of cross-validation (RMSECV) of the transmission mode was 3.9 compared to 4.9 for the backscattering mode. These findings indicate that transmission mode is superior to quantify crystallinity of an API in the pharmaceutical tablet.

Free Research Field

製剤学

Academic Significance and Societal Importance of the Research Achievements

本研究では錠剤中原薬の結晶多形の定量を目的とし透過型低波数ラマン分光法を開発した。本手法は、低波数領域のラマンスペクトルを使用するため、これまで結晶形の把握に汎用されてきた通常領域ラマンスペクトルよりも識別が容易であること、後方散乱測定を透過測定とすることで、定量性を向上させることに成功した。本手法を活用した製品も発売されることからも社会的な意義は大きかったものと考えられる。