Role of excipients in hydrate formation kinetics of theophylline in wet masses studied by near-infrared spectroscopy

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Anna C Jørgensen, Sari Airaksinen, Milja Karjalainen, Pirjo Luukkonen, Jukka Rantanen, Jouko Yliruusi

Hydrate formation is a phase transition, which can occur during wet granulation. This kind of processing-induced transformation (PIT) can influence the quality of a finished product. The aim of the study was to investigate the effect of excipients on the kinetics of hydrate formation in wet masses. Anhydrous theophylline was chosen as the hydrate-forming model drug compound and two excipients, silicified microcrystalline cellulose (SMCC) and alpha-lactose monohydrate, with different water absorbing properties, were used in formulation. An early stage of wet massing was studied with anhydrous theophylline and its 1:1 (w/w) mixtures with alpha-lactose monohydrate and SMCC with 0.1g/g of purified water. The changes in the state of water were monitored using near-infrared spectroscopy, and the conversion of the crystal structure was verified using X-ray powder diffraction (XRPD). SMCC decreased the hydrate formation rate by absorbing water, but did not inhibit it. The results suggest that alpha-lactose monohydrate slightly increased the hydrate formation rate in comparison with a mass comprising only anhydrous theophylline.

Original languageEnglish
JournalEuropean Journal of Pharmaceutical Sciences
Volume23
Issue number1
Pages (from-to)99-104
Number of pages6
ISSN0928-0987
DOIs
Publication statusPublished - Sep 2004

ID: 140622518