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Open AccessArticle

Optimization of the Critical Parameters of the Spherical Agglomeration Crystallization Method by the Application of the Quality by Design Approach

Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, 6720 Szeged, Hungary
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Materials 2018, 11(4), 635; https://doi.org/10.3390/ma11040635
Received: 26 March 2018 / Revised: 12 April 2018 / Accepted: 18 April 2018 / Published: 20 April 2018
(This article belongs to the Section Manufacturing Processes and Systems)
This research work presents the use of the Quality by Design (QbD) concept for optimization of the spherical agglomeration crystallization method in the case of the active agent, ambroxol hydrochloride (AMB HCl). AMB HCl spherical crystals were formulated by the spherical agglomeration method, which was applied as an antisolvent technique. Spherical crystals have good flowing properties, which makes the direct compression tableting method applicable. This means that the amount of additives used can be reduced and smaller tablets can be formed. For the risk assessment, LeanQbD Software was used. According to its results, four independent variables (mixing type and time, dT (temperature difference between solvent and antisolvent), and composition (solvent/antisolvent volume ratio)) and three dependent variables (mean particle size, aspect ratio, and roundness) were selected. Based on these, a 2–3 mixed-level factorial design was constructed, crystallization was accomplished, and the results were evaluated using Statistica for Windows 13 program. Product assay was performed and it was revealed that improvements in the mean particle size (from ~13 to ~200 µm), roundness (from ~2.4 to ~1.5), aspect ratio (from ~1.7 to ~1.4), and flow properties were observed while polymorphic transitions were avoided. View Full-Text
Keywords: spherical crystallization; ambroxol hydrochloride; quality by design; factorial design; statistical analysis; powder rheology analysis; spherical morphology spherical crystallization; ambroxol hydrochloride; quality by design; factorial design; statistical analysis; powder rheology analysis; spherical morphology
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MDPI and ACS Style

Gyulai, O.; Kovács, A.; Sovány, T.; Csóka, I.; Aigner, Z. Optimization of the Critical Parameters of the Spherical Agglomeration Crystallization Method by the Application of the Quality by Design Approach. Materials 2018, 11, 635.

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