Analytical comparison between batch and continuous direct compression processes for pharmaceutical manufacturing using an innovative UV–Vis reflectance method and chemometrics

• Published in: International journal of pharmaceutics Vol. 656; p. 124090
• Main Authors: Macchietti, Laura, Melucci, Dora, Menarini, Lorenzo, Consoli, Fabrizio, Zappi, Alessandro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.05.2024
• Subjects: Continuous direct compression; Continuous mixing; Continuous production process; Multivariate analysis; Pharmaceutical; UV–Vis reflectance; Pharmaceutical; Continuous direct compression; Multivariate analysis; UV–Vis reflectance; Continuous mixing; Continuous production process
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124090

[Display omitted] Advancements in industrial technologies and the application of quality by design (QbD) guidelines are shifting the attention of manufacturers towards innovative production techniques. In the pharmaceutical field, there is a significant focus on the implementation of continuous processes, in which the production stages are carried out continuously, without the need to interrupt the process and store the production intermediates, as in traditional batch production. Such innovative production techniques also require the development of proper analytical methods able to analyze the products in-line, while still being processed. The present study aims to compare a traditional batch manufacturing process with an alternative continuous one. To this end, a real pharmaceutical formulation was used, substituting the active pharmaceutical ingredient (API) with riboflavin, at the concentration of 2 %w/w. Moreover, a direct and non-destructive analytical method based on UV–Vis reflectance spectroscopy was applied for the quantification of riboflavin in the final tablets, and compared with a traditional absorbance analysis. Good results were obtained in the comparison of both the two manufacturing processes and the two analytical methods, with R2 higher than 0.9 for all the calculated calibration models and predicted riboflavin concentrations that never significantly overcame the 15 % limits recommended by the pharmacopeia. The continuous production method demonstrated to be as reliable as the batch one, allowing to save time and money in the production step. Moreover, UV–Vis reflectance was proved to be an interesting alternative to absorption spectroscopy, which, with the proper technology, could be implemented for in-line process control.