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Investigation for the amorphous state of ER-34122, a dual 5-lipoxygenase/cyclooxygenase inhibitor with poor aqueous solubility, in HPMC solid dispersion prepared by the solvent evaporation method.
Drug Dev Ind Pharm. 2013 Oct; 39(10):1582-8.DD

Abstract

ER-34122, a poorly water-soluble dual 5-lipoxygenase/cyclooxygenase inhibitor, exists as a crystalline form. According to an Oak Ridge thermal ellipsoid plot drawing, carbonyl oxygen O (5) makes an intermolecular hydrogen bond with the hydrogen bonded to N (3) in the crystal structure. The FTIR and the solid-state ¹³C NMR spectra suggest that the network is spread out in the amorphous state and the hydrogen bonding gets weaker than that in the crystalline phase, because the carbonyl signals significantly shift in both spectra. When amorphous ER-34122 was heated, crystallization occurred at around 140°C. Similar crystallization happened in the solid dispersion; however, the degree of crystallization was much lower than that observed in the pure amorphous material. Also, the DSC thermogram of the solid dispersion did not show any exothermic peaks implying crystallization. The heat of fusion (ΔHf) determined in the pure amorphous material was nearly equal to that for the crystalline form, whereas the ΔHf value obtained in the solid dispersion was less than a third of them. These data prove that crystallization of the amorphous form is dramatically restrained in the solid dispersion system. The carbonyl wavenumber shifts in the FTIR spectra indicate that the average hydrogen bond in the solid dispersion is lower than that in the pure amorphous material. Therefore, HPMC will suppress formation of the intermolecular network observed in ER-34122 crystal and preserve the amorphous state, which is thermodynamically less stable, in the solid dispersed system.

Authors+Show Affiliations

Analytical Research, CMC Japan, Pharmaceutical Science & Technology Core Function Unit, Eisai Product Creation Systems, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. i-kushida@hhc.eisai.co.jpNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

22519663

Citation

Kushida, Ikuo, and Masaharu Gotoda. "Investigation for the Amorphous State of ER-34122, a Dual 5-lipoxygenase/cyclooxygenase Inhibitor With Poor Aqueous Solubility, in HPMC Solid Dispersion Prepared By the Solvent Evaporation Method." Drug Development and Industrial Pharmacy, vol. 39, no. 10, 2013, pp. 1582-8.
Kushida I, Gotoda M. Investigation for the amorphous state of ER-34122, a dual 5-lipoxygenase/cyclooxygenase inhibitor with poor aqueous solubility, in HPMC solid dispersion prepared by the solvent evaporation method. Drug Dev Ind Pharm. 2013;39(10):1582-8.
Kushida, I., & Gotoda, M. (2013). Investigation for the amorphous state of ER-34122, a dual 5-lipoxygenase/cyclooxygenase inhibitor with poor aqueous solubility, in HPMC solid dispersion prepared by the solvent evaporation method. Drug Development and Industrial Pharmacy, 39(10), 1582-8. https://doi.org/10.3109/03639045.2012.679279
Kushida I, Gotoda M. Investigation for the Amorphous State of ER-34122, a Dual 5-lipoxygenase/cyclooxygenase Inhibitor With Poor Aqueous Solubility, in HPMC Solid Dispersion Prepared By the Solvent Evaporation Method. Drug Dev Ind Pharm. 2013;39(10):1582-8. PubMed PMID: 22519663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation for the amorphous state of ER-34122, a dual 5-lipoxygenase/cyclooxygenase inhibitor with poor aqueous solubility, in HPMC solid dispersion prepared by the solvent evaporation method. AU - Kushida,Ikuo, AU - Gotoda,Masaharu, Y1 - 2012/04/20/ PY - 2012/4/24/entrez PY - 2012/4/24/pubmed PY - 2014/4/16/medline SP - 1582 EP - 8 JF - Drug development and industrial pharmacy JO - Drug Dev Ind Pharm VL - 39 IS - 10 N2 - ER-34122, a poorly water-soluble dual 5-lipoxygenase/cyclooxygenase inhibitor, exists as a crystalline form. According to an Oak Ridge thermal ellipsoid plot drawing, carbonyl oxygen O (5) makes an intermolecular hydrogen bond with the hydrogen bonded to N (3) in the crystal structure. The FTIR and the solid-state ¹³C NMR spectra suggest that the network is spread out in the amorphous state and the hydrogen bonding gets weaker than that in the crystalline phase, because the carbonyl signals significantly shift in both spectra. When amorphous ER-34122 was heated, crystallization occurred at around 140°C. Similar crystallization happened in the solid dispersion; however, the degree of crystallization was much lower than that observed in the pure amorphous material. Also, the DSC thermogram of the solid dispersion did not show any exothermic peaks implying crystallization. The heat of fusion (ΔHf) determined in the pure amorphous material was nearly equal to that for the crystalline form, whereas the ΔHf value obtained in the solid dispersion was less than a third of them. These data prove that crystallization of the amorphous form is dramatically restrained in the solid dispersion system. The carbonyl wavenumber shifts in the FTIR spectra indicate that the average hydrogen bond in the solid dispersion is lower than that in the pure amorphous material. Therefore, HPMC will suppress formation of the intermolecular network observed in ER-34122 crystal and preserve the amorphous state, which is thermodynamically less stable, in the solid dispersed system. SN - 1520-5762 UR - https://www.unboundmedicine.com/medline/citation/22519663/Investigation_for_the_amorphous_state_of_ER_34122_a_dual_5_lipoxygenase/cyclooxygenase_inhibitor_with_poor_aqueous_solubility_in_HPMC_solid_dispersion_prepared_by_the_solvent_evaporation_method_ L2 - https://www.tandfonline.com/doi/full/10.3109/03639045.2012.679279 DB - PRIME DP - Unbound Medicine ER -