کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2084505 1545391 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Physical characterization and stability of amorphous indomethacin and ranitidine hydrochloride binary systems prepared by mechanical activation
چکیده انگلیسی

Co-milling of γ-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 °C). The maximum temperature of the solid material was 42 °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 Tgs of the fully converted amorphous mixtures of 29.3, 32.5 and 34.3 °C were measured for the 1:2, 1:1 and 2:1 mixtures, respectively. These Tg values were in good agreement with the predicted Tgs 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–CO) and benzonyl amide (NCO) of the indomethacin molecule with the aci-nitro (CN) 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 °C (for the 2:1 mixture) and at 4 and 25 °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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 71, Issue 1, January 2009, Pages 47–54
نویسندگان
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