Abstract
We have developed the vacuum dryer attached XRD-DSC system and monitored manufacturing process of freeze-dried pharmaceutical product. The aim of this study is to apply the XRD-DSC system for the preformulation of freeze-dried injections. Gabexate mesilate was used as a model drug. Drug solution was frozen then heated to annealing temperature according to the process-controlling program. The XRD-DSC analyses were performed to monitor the crystallized spicies and their crystallinity of sample. When the solution was cooled slowly, peaks of gabexate mesilate and mannitol polymorph had been already observed during the cooling process while those crystallinity were low at fast cooling rate. As the drying underwent, intensity of ice peaks were getting weaker. At the cooling rate of 0.1°C min–1, the XRD profile of final product was revealed that the characteristic peaks of gabexate mesilate, mannitol δ-form and β-form were appeared. When the cooling rate was increased, the crystallinity of final products was decreased. From these results, it was confirmed that the XRD profiles during freeze-drying process significantly related to the final freeze-dried product. It is obvious that monitoring by XRD-DSC system is a quite effective way to simulate the manufacturing process and to optimize the qualified product.
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References
Y Suzuki (1998) J. Jpn. Soc. Pharm. Mach Eng. 7 107
A Pyne R Suryanarayanan (2001) Pharm. Res. 18 1448 Occurrence Handle1:CAS:528:DC%2BD3MXotVShsb4%3D Occurrence Handle10.1023/A:1012209007411
A Pyne R Surana R Suryanarayanan (2002) Pharm. Res. 19 901 Occurrence Handle1:CAS:528:DC%2BD38XltVSgtrc%3D Occurrence Handle10.1023/A:1016129521485
A Pyne R Suryanarayanan (2003) Pharm. Res. 20 283 Occurrence Handle1:CAS:528:DC%2BD3sXpslWhsw%3D%3D Occurrence Handle10.1023/A:1022239608095
TG Fawcett CE Crowder LF Witing JC Tou WF Scott RA Newman WC Harris FJ Knoll (1985) V. J., Adv., X-Ray Anal. 28 227 Occurrence Handle1:CAS:528:DyaL28XhsF2qu7w%3D
G Keller F Lavigne L Forte K Andrieux M Dahim C Loisel M Ollivon C Bourgaux P Lesieur (1998) J. Thermal. Anal. 51 783 Occurrence Handle1:CAS:528:DyaK1cXns1Cms7k%3D
D Lexa (1999) Rev. Sci. Instrum. 70 2242 Occurrence Handle1:CAS:528:DyaK1MXivVSms7o%3D Occurrence Handle10.1063/1.1149745
T Arii A Kishi Y Kobayashi (1999) Themochim. Acta 325 151 Occurrence Handle1:CAS:528:DyaK1MXivVOmuw%3D%3D Occurrence Handle10.1016/S0040-6031(98)00573-5
EY Shalaev F Franks (1995) J. Chem. Soc. Faraday Trans 91 512 Occurrence Handle10.1039/ft9959101511
S Ablett MJ Izzard PJ Lillford (1992) J. Chem. Soc. Faraday Trans. 88 789 Occurrence Handle1:CAS:528:DyaK38XitFCrsrs%3D Occurrence Handle10.1039/ft9928800789
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Yonemochi, E., Yoshioka, Y., Yoshihashi, Y. et al. Application of XRD-DSC system to the optimization of manufacturing process for the freeze-dried pharmaceuticals. J Therm Anal Calorim 85, 693–697 (2006). https://doi.org/10.1007/s10973-005-7655-y
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DOI: https://doi.org/10.1007/s10973-005-7655-y