کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1222407 | 967863 | 2011 | 6 صفحه PDF | دانلود رایگان |
Molecular weight distribution is an important quality attribute for hypromellose acetate succinate (HPMCAS), a pharmaceutical excipient used in spray-dried dispersions. Our previous study showed that neither relative nor universal calibration method of size exclusion chromatography (SEC) works for HPMCAS polymers. We here report our effort to develop a SEC method using a mass sensitive multi angle laser light scattering detector (MALLS) to determine molecular weight distributions of HPMCAS polymers. A solvent screen study reveals that a mixed solvent (60:40%, v/v 50 mM NaH2PO4 with 0.1 M NaNO3 buffer: acetonitrile, pH* 8.0) is the best for HPMCAS-LF and MF sub-classes. Use of a mixed solvent creates a challenging condition for the method that uses refractive index detector. Therefore, we thoroughly evaluated the method performance and robustness. The mean weight average molecular weight of a polyethylene oxide standard has a 95% confidence interval of (28,443–28,793) g/mol vs. 28,700 g/mol from the Certificate of Analysis. The relative standard deviations of average molecular weights for all polymers are 3–6%. These results and the Design of Experiments study demonstrate that the method is accurate and robust.
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 56, Issue 4, 5 December 2011, Pages 743–748