Crystallization and physicochemical investigation of melevodopa hydrochloride, a commercially available antiparkinsonian active substance / Tamás Kiss, Gábor Katona, Rita Ambrus
Bibliogr.: p. 52. - Abstr. eng. - DOI: https://doi.org/10.33892/aph.2021.91.45-52
In: Acta Pharmaceutica Hungarica. - ISSN 0001-6659. - 2021. 91. évf. 2. sz., p. 45-52. : ill.
Abstract: In this work, the levodopa methyl ester was crystallized from different solvents and its physicochemical proper ties were explored. This active pharmaceutical ingredient (API) is commercially available as an effervescent tablet in Italy. The crystallization methods were solvent evaporation from different solvents (water, ethanol, methanol) and crystalliza tion by adding an antisolvent. These methods led to the same product which had the same different Xray powder diffrac togram that was different from the diffractogram of LDMEI. According to the hotstage microscopy and differential scan ning calorimetry (DSC), the melting point was remarkably decreased, however, above the melting point, the melt tended to recrystallize to the LDMEI which was shown by an exothermic peak on the DSC curve. This was verified by an additional test during which the API was heated to 145 °C, thereafter the diffractogram matched perfectly with the LDMEI. These results indicate the presumable formation of a new polymorph. During the crystallization, the LDME did not degrade ac cording to the high-performance liquid chromatography. Besides the recrystallization kinetics of the amorphous form was also followed, the activation energy of recrystallization was 85.3 kJ/mol, the diffractogram of recrystallization was the same as in the case of the crystallized products. Kulcsszavak: melevodopa hydrochloride, crystallization, potential polymorph, melting point, X-ray powder diffractometry