New Thermoresistant Polymorph from CO2 Recrystallization of Minocycline Hydrochloride

Abstract

This work describes a new crystalline structure of minocycline and evidences the ability of ethanol-CO2 system in removing water molecules from the crystalline structure of this API, at modest pressure, temperature and relatively short time (2 h), while controlling the crystal habit. This process has therefore the potential to become a consistent alternative towards the control of the solid form of APIs.

Crystal structure of minocycline hydrochloride dihydrate form A, C23H28N3O7Cl (H2O)2

“…(2012) and that of “ α -minocycline hydrochloride” from Rodrigues et al . (2014) well enough to conclude that the materials are the same (Figure 3). The material studied by Rodrigues et al .…”

“…The material studied by Rodrigues et al . (2014) was also a commercial sample, so we can conclude that the material studied here is representative of that actually used in the market.

Figure 3.(Color online) Comparison of the synchrotron pattern to that of minocycline hydrochloride dihydrate from Figure 1 of Chinese Patent Application101693669B (reported as hydrate) and Figure 4 from Rodrigues et al .

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Figure 3.(Color online) Comparison of the synchrotron pattern to that of minocycline hydrochloride dihydrate from Figure 1 of Chinese Patent Application101693669B (reported as hydrate) and Figure 4 from Rodrigues et al . (2014). The Literature patterns (measured using Cu K α radiation) were digitized using UN-SCAN-IT, and re-scaled to the synchrotron wavelength of 0.414163 Å using Jade 9.8.

Figure 4.(Color online) Comparison of the refined and optimized (CRYSTAL14) structures of the cation in minocycline hydrochloride dihydrate.

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“…A powder pattern for “ α -minocycline hydrochloride” (which corresponds to Form A of the Chinese patent) is reported in Rodrigues et al . (2014), as well as a new β polymorph.…”

“…Form B crystallizes in P3 1 21 with a = 13.143, c = 27.417(7) Å, V = 4101.85 Å 3 , and Z = 6. A powder pattern for "α-minocycline hydrochloride" (which corresponds to Form A of the Chinese patent) is reported in Rodrigues et al (2014), as well as a new β polymorph.…”