Polymorphic characterization and implications on biopharmaceutics properties of potential anti-inflammatory drug candidate eremantholide C from Lychnophora trichocarpha (Brazilian arnica)

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Resumo

Objectives: To perform the polymorphic and physicochemical characterization of the potential anti-inflammatory drug, eremantholide C (EREC), as well as to evaluate the influence of these characteristics on its biopharmaceutics classification. Methods: Eremantholide C was obtained from chloroformic extract of Lychnophora trichocarpha and crystallized in two distinct solvents: chloroform (EREC 1) and ethyl acetate (EREC 2). To evaluate the polymorphism, EREC samples were submitted to melting point, purity, infrared spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction, optical microscopy and scanning electron microscopy analysis. In addition, EREC samples crystallized after intrinsic dissolution study were submitted to DSC and X-ray powder diffraction analysis. Key findings: EREC 1 showed fusion at 234.7–241.6 °C, while EREC 2 showed fusion at 238.6–243.7 °C. No polymorphic transitions were observed during the intrinsic dissolution experiment. A single sharp endothermic peak was obtained for the EREC samples. X-ray diffraction showed no crystallographic differences between the EREC samples. EREC 1 and EREC 2 showed birefringence under polarized light and indefinite morphology; however, the shape of the crystals was common to the two samples. Conclusions: Eremantholide C does not present classical or morphological polymorphism; therefore, there is no influence of crystalline transitions in the solubility and consequently in its biopharmaceutics classification and oral absorption process.

Abstract

Assunto

Físico-química, Biofarmacêutica, Polimorfismo (Cristalografia), Agentes antiinflamatórios, Arnica, Solubilidade, Raios X - Difração, Espectroscopia de infravermelho, Calorimetria, Microscopia

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Differential scanning calorimetry, Eremantholide C, Intrinsic dissolution, Polymorphism, Solubility, X-ray powder, Diffraction

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https://academic.oup.com/jpp/article/71/6/910/6122148

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