Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation

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Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation. / Chieng, Norman; Aaltonen, Jaakko; Saville, Dorothy; Rades, Thomas.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 71, No. 1, 01.2009, p. 47-54.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Chieng, N, Aaltonen, J, Saville, D & Rades, T 2009, 'Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation', European Journal of Pharmaceutics and Biopharmaceutics, vol. 71, no. 1, pp. 47-54. https://doi.org/10.1016/j.ejpb.2008.06.022

APA

Chieng, N., Aaltonen, J., Saville, D., & Rades, T. (2009). Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation. European Journal of Pharmaceutics and Biopharmaceutics, 71(1), 47-54. https://doi.org/10.1016/j.ejpb.2008.06.022

Vancouver

Chieng N, Aaltonen J, Saville D, Rades T. Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation. European Journal of Pharmaceutics and Biopharmaceutics. 2009 Jan;71(1):47-54. https://doi.org/10.1016/j.ejpb.2008.06.022

Author

Chieng, Norman ; Aaltonen, Jaakko ; Saville, Dorothy ; Rades, Thomas. / Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation. In: European Journal of Pharmaceutics and Biopharmaceutics. 2009 ; Vol. 71, No. 1. pp. 47-54.

Bibtex

@article{2eee234129094a3e9451f94be3af7640,
title = "Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation",
abstract = "Co-milling of gamma-indomethacin and ranitidine hydrochloride form 2 at various weight ratios (1:2, 1:1 and 2:1) was investigated with a particular interest in the physicochemical properties and the stability of the milled mixed amorphous form. Co-milling was carried out using an oscillatory ball mill for various periods of time up to 60 min in a cold room (4 degrees C). The maximum temperature of the solid material was 42 degrees C during co-milling in a cold room. Results showed that both indomethacin and ranitidine hydrochloride were fully converted into the amorphous state after 60 min of co-milling. In contrast individually milled drugs remained partially crystalline after co-milling under the same conditions. During co-milling, the XRPD characteristic peaks of indomethacin were found to decrease faster than those of ranitidine hydrochloride. DSC results were in agreement with XRPD, and T(g)s of the fully converted amorphous mixtures of 29.3, 32.5 and 34.3 degrees C were measured for the 1:2, 1:1 and 2:1 mixtures, respectively. These T(g) values were in good agreement with the predicted T(g)s of the mixtures using the Gordon-Taylor equation. DRIFTS spectra of the co-milled amorphous samples showed peaks at 1610, 1679 and 1723 cm(-1), that were not present in the individually milled samples and that are indicative of an interaction at the carboxylic acid carbonyl (HO-C=O) and benzonyl amide (N=CO) of the indomethacin molecule with the aci-nitro (C=N) of ranitidine hydrochloride. Upon 30 days of storage, the 1:2 mixtures were found to crystallize; however, the amorphous 2:1 and 1:1 mixtures were stable when milled for 60 min and stored at 4 degrees C (for the 2:1 mixture) and at 4 and 25 degrees C (for the 1:1 mixture), respectively. Although XRPD, DSC and DRIFTS suggested an interaction between the two drugs, co-crystal formation was not observed between indomethacin and ranitidine hydrochloride.",
author = "Norman Chieng and Jaakko Aaltonen and Dorothy Saville and Thomas Rades",
year = "2009",
month = jan,
doi = "10.1016/j.ejpb.2008.06.022",
language = "English",
volume = "71",
pages = "47--54",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation

AU - Chieng, Norman

AU - Aaltonen, Jaakko

AU - Saville, Dorothy

AU - Rades, Thomas

PY - 2009/1

Y1 - 2009/1

N2 - Co-milling of gamma-indomethacin and ranitidine hydrochloride form 2 at various weight ratios (1:2, 1:1 and 2:1) was investigated with a particular interest in the physicochemical properties and the stability of the milled mixed amorphous form. Co-milling was carried out using an oscillatory ball mill for various periods of time up to 60 min in a cold room (4 degrees C). The maximum temperature of the solid material was 42 degrees C during co-milling in a cold room. Results showed that both indomethacin and ranitidine hydrochloride were fully converted into the amorphous state after 60 min of co-milling. In contrast individually milled drugs remained partially crystalline after co-milling under the same conditions. During co-milling, the XRPD characteristic peaks of indomethacin were found to decrease faster than those of ranitidine hydrochloride. DSC results were in agreement with XRPD, and T(g)s of the fully converted amorphous mixtures of 29.3, 32.5 and 34.3 degrees C were measured for the 1:2, 1:1 and 2:1 mixtures, respectively. These T(g) values were in good agreement with the predicted T(g)s of the mixtures using the Gordon-Taylor equation. DRIFTS spectra of the co-milled amorphous samples showed peaks at 1610, 1679 and 1723 cm(-1), that were not present in the individually milled samples and that are indicative of an interaction at the carboxylic acid carbonyl (HO-C=O) and benzonyl amide (N=CO) of the indomethacin molecule with the aci-nitro (C=N) of ranitidine hydrochloride. Upon 30 days of storage, the 1:2 mixtures were found to crystallize; however, the amorphous 2:1 and 1:1 mixtures were stable when milled for 60 min and stored at 4 degrees C (for the 2:1 mixture) and at 4 and 25 degrees C (for the 1:1 mixture), respectively. Although XRPD, DSC and DRIFTS suggested an interaction between the two drugs, co-crystal formation was not observed between indomethacin and ranitidine hydrochloride.

AB - Co-milling of gamma-indomethacin and ranitidine hydrochloride form 2 at various weight ratios (1:2, 1:1 and 2:1) was investigated with a particular interest in the physicochemical properties and the stability of the milled mixed amorphous form. Co-milling was carried out using an oscillatory ball mill for various periods of time up to 60 min in a cold room (4 degrees C). The maximum temperature of the solid material was 42 degrees C during co-milling in a cold room. Results showed that both indomethacin and ranitidine hydrochloride were fully converted into the amorphous state after 60 min of co-milling. In contrast individually milled drugs remained partially crystalline after co-milling under the same conditions. During co-milling, the XRPD characteristic peaks of indomethacin were found to decrease faster than those of ranitidine hydrochloride. DSC results were in agreement with XRPD, and T(g)s of the fully converted amorphous mixtures of 29.3, 32.5 and 34.3 degrees C were measured for the 1:2, 1:1 and 2:1 mixtures, respectively. These T(g) values were in good agreement with the predicted T(g)s of the mixtures using the Gordon-Taylor equation. DRIFTS spectra of the co-milled amorphous samples showed peaks at 1610, 1679 and 1723 cm(-1), that were not present in the individually milled samples and that are indicative of an interaction at the carboxylic acid carbonyl (HO-C=O) and benzonyl amide (N=CO) of the indomethacin molecule with the aci-nitro (C=N) of ranitidine hydrochloride. Upon 30 days of storage, the 1:2 mixtures were found to crystallize; however, the amorphous 2:1 and 1:1 mixtures were stable when milled for 60 min and stored at 4 degrees C (for the 2:1 mixture) and at 4 and 25 degrees C (for the 1:1 mixture), respectively. Although XRPD, DSC and DRIFTS suggested an interaction between the two drugs, co-crystal formation was not observed between indomethacin and ranitidine hydrochloride.

U2 - 10.1016/j.ejpb.2008.06.022

DO - 10.1016/j.ejpb.2008.06.022

M3 - Journal article

C2 - 18644443

VL - 71

SP - 47

EP - 54

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

IS - 1

ER -

ID: 40349157