Real-time monitoring of pharmaceutical properties of medical tablets during direct tableting process by hybrid tableting process parameter–time profiles

Article type: Research Article

Authors: Saito, Shuji^a | Hattori, Yusuke^a | Sakamoto, Tomoaki^b | Otsuka, Makoto^a;

Affiliations: [a] Graduate School of Pharmaceutical Sciences, Musashino University, Nishi-Tokyo, Tokyo, Japan | [b] Division of Drugs, National Institute of Health Sciences, Kawasaki-ku, Kawasaki City, Kanagawa, Japan

Correspondence: [*] Corresponding author: Makoto Otsuka, Graduate School of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishi-Tokyo, Tokyo 202-8585, Japan. Tel. and Fax: +81 042 468 8658; E-mail: motsuka@musashino-u.ac.jp

Abstract: BACKGROUND:Real-time monitoring is required for the pharmaceutical manufacturing process to produce high-quality pharmaceutical products. OBJECTIVE:Changes in the critical tableting process parameters of single-punch tableting machine due to variability in the moisture content of the raw powders were monitored by hybrid tableting pressure–time profiles. METHODS:After mixing of the raw powders, which consisted of theophylline, anhydrous lactose, potato starch and crystalline cellulose, they were stored at 0%, 45%, or 75% relative humidity (RH) for 24 h, respectively. Continuous tablet productions were carried out using the mixed powder samples at 10%, 45%, or 75% RH, respectively. The critical process parameters, such as upper and lower puncture pressures, die wall pressures, and inter-punch distances were recoded with the tableting machine, and then, tablet hardness (H), weight (W) and disintegration time (DT) of the tablets were measured. RESULTS:Hybrid tableting pressure–time profiles were obtained from various critical process parameters, and calibration models to predict pharmaceutical properties were calculated based on the hybrid profiles using a partial-least-squares regression (PLSR) method. In addition, the consistency of the calibration models were verified by constructing robust calibration models. CONCLUSION:Informetrical analysis for tablets based on hybrid tableting pressure–time profiles could evaluate the change of tablet properties dependent on the moisture content in the raw powders during the tableting process. The changes of tableting properties and elasticity were caused by agglomeration of powder particles at moisture content.

Keywords: Tableting compression, effect of moisture content, process analytical technology, hybrid tableting pressure–time profiles, tablet hardness, tablet disintegration time, partial-least-squares-regression

DOI: 10.3233/BME-191071

Journal: Bio-Medical Materials and Engineering, vol. 30, no. 5-6, pp. 509-524, 2019