MilliporeSigma
  • Home
  • Search Results
  • Coformer screening using thermal analysis based on binary phase diagrams.

Coformer screening using thermal analysis based on binary phase diagrams.

Pharmaceutical research (2014-02-14)
Hiroyuki Yamashita, Yutaka Hirakura, Masamichi Yuda, Katsuhide Terada
ABSTRACT

The advent of cocrystals has demonstrated a growing need for efficient and comprehensive coformer screening in search of better development forms, including salt forms. Here, we investigated a coformer screening system for salts and cocrystals based on binary phase diagrams using thermal analysis and examined the effectiveness of the method. Indomethacin and tenoxicam were used as models of active pharmaceutical ingredients (APIs). Physical mixtures of an API and 42 kinds of coformers were analyzed using Differential Scanning Calorimetry (DSC) and X-ray DSC. We also conducted coformer screening using a conventional slurry method and compared these results with those from the thermal analysis method and previous studies. Compared with the slurry method, the thermal analysis method was a high-performance screening system, particularly for APIs with low solubility and/or propensity to form solvates. However, this method faced hurdles for screening coformers combined with an API in the presence of kinetic hindrance for salt or cocrystal formation during heating or if there is degradation near the metastable eutectic temperature. The thermal analysis and slurry methods are considered complementary to each other for coformer screening. Feasibility of the thermal analysis method in drug discovery practice is ensured given its small scale and high throughput.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Aspartic acid, BioXtra, ≥99% (HPLC)
Sigma-Aldrich
L-Aspartic acid, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
L-Aspartic acid, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
Urea solution, 40 % (w/v) in H2O
Sigma-Aldrich
Saccharin, ≥99%
Sigma-Aldrich
N-Acetylglycine, ReagentPlus®, 99%
Sigma-Aldrich
Urea-12C, 99.9 atom % 12C
Sigma-Aldrich
Saccharin, ≥98%
Sigma-Aldrich
Urea solution, BioUltra, ~8 M in H2O
Sigma-Aldrich
L-Pyroglutamic acid, ≥99.0% (T)
Sigma-Aldrich
L-Aspartic acid, BioUltra, ≥99.5% (T)
Supelco
Mettler-Toledo Calibration substance ME 18555, Benzoic acid, analytical standard, for the calibration of the thermosystem 900, traceable to primary standards (LGC)
Sigma-Aldrich
Mucic acid, 97%
SAFC
L-Aspartic acid
Sigma-Aldrich
L-Pyroglutamic acid, BioXtra
Sigma-Aldrich
Meglumine, meets USP testing specifications
Sigma-Aldrich
L-Aspartic acid, ≥98%, FG
Supelco
L-Aspartic acid, certified reference material, TraceCERT®
Supelco
L-Aspartic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Millipore
Urea solution, suitable for microbiology, 40% in H2O
Supelco
Saccharin, Pharmaceutical Secondary Standard; Certified Reference Material
Meglumine, European Pharmacopoeia (EP) Reference Standard
Saccharin, European Pharmacopoeia (EP) Reference Standard
USP
Saccharin, United States Pharmacopeia (USP) Reference Standard
Supelco
Meglumine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Urea, ReagentPlus®, ≥99.5%, pellets
Sigma-Aldrich
Urea, ACS reagent, 99.0-100.5%
Sigma-Aldrich
Citric acid, 99%
Sigma-Aldrich
Giemsa stain, certified by the Biological Stain Commission
Sigma-Aldrich
Urea, meets USP testing specifications