کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2484933 1114340 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Investigation of Metformin HCl Lot-to-Lot Variation on Flowability Differences Exhibited during Drug Product Processing
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Investigation of Metformin HCl Lot-to-Lot Variation on Flowability Differences Exhibited during Drug Product Processing
چکیده انگلیسی
The purpose of this study was to determine the cause for flowability difference observed during drug product processing when different Metformin HCl drug substance batches of varying age were used. It was found that the lead time (age) between the final step (milling) in the manufacturing process of the Metformin HCl drug substance could be a factor. The lead time had an impact on flowability of Metformin/excipient blends during drug product processing even though these batches had no apparent differences in their release specifications. To study and understand the aging effect, two batches of Metformin HCl manufactured at different periods of time were selected. The surface energy values obtained by the density functional theory (DFT) method together with X-ray diffraction patterns, thermally stimulated current measurements, and dynamic vapor sorption isotherms indicated that the freshly manufactured Metformin HCl material contains detectable amounts of surface crystal defects, but are absent in aged sample, which could be the cause of flowability differences of Metformin/excipient blends observed during the drug product processing. Having identified the cause for different flow behavior, a method to destroy these defects was designed and the issue was resolved by rapid aging of Metformin HCl under humidity at room temperature.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 12, December 2010, Pages 5030-5039
نویسندگان
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