Real‐Time Monitoring of Changes of Adsorbed and Crystalline Water Contents in Tablet Formulation Powder Containing Theophylline Anhydrate at Various Temperatures During Agitated Granulation by Near‐Infrared Spectroscopy

• Published in: Journal of pharmaceutical sciences 2014-09, Vol.103 (9), p.2924-2936
• Main Authors: Otsuka, Makoto, Kanai, Yoshinori, Hattori, Yusuke
• Format: Article
• Language: English
• Subjects: Adsorption; Chemistry, Pharmaceutical - methods; chemometric near‐infrared spectroscopy; chemometrics; crystal engineering; Crystallization - methods; Desiccation - methods; dissolution test; Drug Compounding - methods; Hardness; hydration; particle size; Porosity; Powders - chemistry; process analysis technology; real‐time monitoring during agitated granulation; Spectroscopy, Near-Infrared - methods; tablet hardness; Tablets - chemistry; Temperature; temperature effect on pseudo‐polymorphic transformation; Theophylline - chemistry; theophylline anhydrate tablet formulation; Water - chemistry
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.24006

Real‐time monitoring of adsorbed water content (FW) and hydrate formation of theophylline anhydrate (THA) in tablet formulation during agitated granulation was investigated by near‐infrared (NIR) spectroscopy. As the wet‐granulation process of THA tablet formulation involves change in pseudo‐polymorphs between THA and theophylline monohydrate (THM), the pharmaceutical properties of THA tablet depend on the degree of hydration during granulation. After mixing of the powder materials (4 g) containing THA, and excipients and the addition of 600 μL of binding water, the powder was kneaded at 27°C, 40°C, and 50°C and then dried. The mixing, granulating, and drying processes were monitored using NIR. The calibration models to predict THM and total water contents during granulation in THA tablet formulation were obtained by partial least‐squares regression. The FW in the formulation was determined by subtracting THM from the water content. The results of the THA formulation powder bed during granulation by NIR monitoring indicated that the transformation pathway of the THA powder was THA ⇒ THM ⇒ THA at 27°C and 40°C, but that at 50°C was THA ⇒ THA ⇒ THA. The pharmaceutical properties, such as tablet porosity, hardness, tablet disintegration time, and dissolution rate of the final THA tablet products, were affected by the degree of crystalline transformation during granulation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2924–2936, 2014