Michał Teżyk1,2, Emilia Jakubowska2, Kasylda Milczewska3, Bartłomiej Milanowski2, Adam Voelkel3, Janina Lulek2. 1. a Gedeon Richter Polska Sp. z o.o , Grodzisk Mazowiecki , Poland. 2. b Department of Pharmaceutical Technology, Faculty of Pharmacy , Poznan University of Medical Sciences , Poznan , Poland. 3. c Institute of Chemical Technology and Engineering, Poznan University of Technology , Poznan , Poland.
Abstract
OBJECTIVE: The aim of this article is to compare the gravitational powder blend loading method to the tablet press and manual loading in terms of their influence on tablets' critical quality attributes (CQA). SIGNIFICANCE: The results of the study can be of practical relevance to the pharmaceutical industry in the area of direct compression of low-dose formulations, which could be prone to content uniformity (CU) issues. METHODS: In the preliminary study, particle size distribution (PSD) and surface energy of raw materials were determined using laser diffraction method and inverse gas chromatography, respectively. For trials purpose, a formulation containing two pharmaceutical ingredients (APIs) was used. Tablet samples were collected during the compression progress to analyze their CQAs, namely assay and CU. RESULTS: Results obtained during trials indicate that tested direct compression powder blend is sensitive to applied powder handling method. Mild increase in both APIs content was observed during manual scooping. Gravitational approach (based on discharge into the drum) resulted in a decrease in CU, which is connected to a more pronounced assay increase at the end of tableting than in the case of manual loading. CONCLUSIONS: The correct design of blend transfer over single unit processes is an important issue and should be investigated during the development phase since it may influence the final product CQAs. The manual scooping method, although simplistic, can be a temporary solution to improve the results of API's content and uniformity when compared to industrial gravitational transfer.
OBJECTIVE: The aim of this article is to compare the gravitational powder blend loading method to the tablet press and manual loading in terms of their influence on tablets' critical quality attributes (CQA). SIGNIFICANCE: The results of the study can be of practical relevance to the pharmaceutical industry in the area of direct compression of low-dose formulations, which could be prone to content uniformity (CU) issues. METHODS: In the preliminary study, particle size distribution (PSD) and surface energy of raw materials were determined using laser diffraction method and inverse gas chromatography, respectively. For trials purpose, a formulation containing two pharmaceutical ingredients (APIs) was used. Tablet samples were collected during the compression progress to analyze their CQAs, namely assay and CU. RESULTS: Results obtained during trials indicate that tested direct compression powder blend is sensitive to applied powder handling method. Mild increase in both APIs content was observed during manual scooping. Gravitational approach (based on discharge into the drum) resulted in a decrease in CU, which is connected to a more pronounced assay increase at the end of tableting than in the case of manual loading. CONCLUSIONS: The correct design of blend transfer over single unit processes is an important issue and should be investigated during the development phase since it may influence the final product CQAs. The manual scooping method, although simplistic, can be a temporary solution to improve the results of API's content and uniformity when compared to industrial gravitational transfer.