Effect of Different Direct Compaction Grades of Mannitol on the Storage Stability of Tablet Properties Investigated Using a Kohonen Self-Organizing Map and Elastic Net Regression Model

Abstract

This study tested 15 direct compaction grades to identify the contribution of different grades of mannitol to the storage stability of the resulting tablets. After preparing the model tablets with different values of hardness, they were stored at 25 °C, 75% relative humidity for 1 week. Then, measurement of the tablet properties was conducted on both pre- and post-storage tablets. The tablet properties were tensile strength (TS), friability, and disintegration time (DT). The experimental data were analyzed using a Kohonen self-organizing map (SOM). The SOM analysis successfully classified the test grades into three distinct clusters having different changes in the behavior of the tablet properties accompanying storage. Cluster 1 showed an obvious rise in DT induced by storage, while cluster 3 showed a substantial change in mechanical strength of the tablet including a reduction in the TS and a rise in friability. Furthermore, the data were analyzed using an Elastic net regression technique to investigate the general relationships between the powder properties of mannitol and the change behavior of the tablet properties. Consequently, we succeeded in identifying the crucial powder properties for the storage stability of the resulting tablets. This study provides advanced technical knowledge to characterize the effect of different direct compaction grades of mannitol on the storage stability of tablet properties.

Surface Modifiers on Composite Particles for Direct Compaction

“…The tablet is still the most commonly used solid form due to its dose accuracy, convenience, stability, and ease of production in large quantities [ 1 , 2 , 3 , 4 ]. Direct compaction (DC) is the most preferred and is the first choice for tableting [ 5 , 6 , 7 ]. DC has many advantages over dry and wet granulation, such as eliminating heat and moisture effects, reducing costs and turnaround times, ensuring continuity, simplifying the process, and enhancing bioavailability [ 8 , 9 , 10 , 11 , 12 ].…”

Discovery of potential Q‐marker of traditional Chinese medicine based on chemical profiling, chemometrics, network pharmacology, and molecular docking: Centipeda minima as an example

“…CP‐ANN was developed based on the Kohonen network and can deal with both unsupervised and supervised classification problems 21 . CP‐ANN was used as a supervised model to analyze and verify the results of sample classification, and the role of variables in classification was studied.…”

Spray Drying for Direct Compression of Pharmaceuticals

“…Spray-dried mannitol is commercially available in two grades: the 100 or EZ and 200 or XL with the former having smaller mean particle size [70]. Unlike lactose, spray drying does not affect its crystallinity with the final product being comprised of β crystals (Parteck ® ) or a mixture of α and β mannitol crystals (Pearlitol ® , and Mannogem ® ) [71,72]. Recently, the powder and tablet properties of several brands and grades of spray-dried mannitol were compared with commercially available granulated grades [70,72].…”

“…Unlike lactose, spray drying does not affect its crystallinity with the final product being comprised of β crystals (Parteck ® ) or a mixture of α and β mannitol crystals (Pearlitol ® , and Mannogem ® ) [71,72]. Recently, the powder and tablet properties of several brands and grades of spray-dried mannitol were compared with commercially available granulated grades [70,72]. Except for a minor increase in the disintegration time observed after one-week storage (25 • C/75% RH), the tablets of spray-dried mannitol grades showed superior physical stability over the granulation-based grades.…”