title: Quantitative determination of solid-state forms of a pharmaceutical development compound in drug substance and tablets.
abstract: Common analytical techniques including Raman, NIR, and XRD were evaluated for quantitative determination of three solid-state forms (amorphous, Form B and Form C) of a development compound. Raman spectroscopy was selected as the primary analytical technique with sufficient sensitivity to monitor and quantify the neat drug substance alone and in the drug product. A reliable multivariate curve resolution (MCR) method based on the second derivative Raman measurements of the three pure physical forms was developed and validated with 3.5% root mean square error of prediction (RMSEP) for Form B, which was selected as the preferred form for further development. A partial least squares (PLS) algorithm was also used for the multivariate calibration of both the NIR and Raman measurements. The long-term stability of Form B as a neat active pharmaceutical ingredient (API) and in a tablet formulation was quantitatively monitored under various stress conditions of temperature and moisture. Moisture, temperature, excipients and compression were found to have significant effects on the phase transition behavior of Form B.
authors.affiliation: Pharmaceutics Department, Amgen Inc., One Amgen Center Dr., Thousand Oaks, CA 91320, USA. yongx@amgen.com
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
authors.forename: Wenle
authors.initials: W
authors.lastname: Tao
authors.forename: Henry
authors.initials: H
authors.lastname: Morrison
authors.forename: Rick
authors.initials: R
authors.lastname: Chiu
authors.forename: Janan
authors.initials: J
authors.lastname: Jona
authors.forename: Jan
authors.initials: J
authors.lastname: Fang
authors.forename: Nina
authors.initials: N
authors.lastname: Cauchon
mesh_terms: D002626:Chemistry, Pharmaceutical; D019245:Compressive Strength; D015195:Drug Design; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015999:Multivariate Analysis; D044367:Phase Transition; D013059:Spectrum Analysis, Raman; D013607:Tablets / Q000032:analysis* / Q000737:chemistry*; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D013607:Tablets