کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2503639 1557437 2011 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Quality-by-Design (QbD): An integrated process analytical technology (PAT) approach for a dynamic pharmaceutical co-precipitation process characterization and process design space development
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Quality-by-Design (QbD): An integrated process analytical technology (PAT) approach for a dynamic pharmaceutical co-precipitation process characterization and process design space development
چکیده انگلیسی

The aim of this work was to develop an integrated process analytical technology (PAT) approach for a dynamic pharmaceutical co-precipitation process characterization and design space development. A dynamic co-precipitation process by gradually introducing water to the ternary system of naproxen–Eudragit L100–alcohol was monitored at real-time in situ via Lasentec FBRM and PVM. 3D map of count-time-chord length revealed three distinguishable process stages: incubation, transition, and steady-state. The effects of high risk process variables (slurry temperature, stirring rate, and water addition rate) on both derived co-precipitation process rates and final chord-length-distribution were evaluated systematically using a 33 full factorial design. Critical process variables were identified via ANOVA for both transition and steady state. General linear models (GLM) were then used for parameter estimation for each critical variable. Clear trends about effects of each critical variable during transition and steady state were found by GLM and were interpreted using fundamental process principles and Nyvlt's transfer model. Neural network models were able to link process variables with response variables at transition and steady state with R2 of 0.88–0.98. PVM images evidenced nucleation and crystal growth. Contour plots illustrated design space via critical process variables’ ranges. It demonstrated the utility of integrated PAT approach for QbD development.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 405, Issues 1–2, 28 February 2011, Pages 63–78
نویسندگان
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