Jørgensen Anna C, Airaksinen Sari, Karjalainen Milja, Luukkonen Pirjo, Rantanen Jukka, Yliruusi Jouko
Pharmaceutical Technology Division, Department of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland.
Eur J Pharm Sci. 2004 Sep;23(1):99-104. doi: 10.1016/j.ejps.2004.06.001.
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.
水合物形成是一种相变，它可能在湿法制粒过程中发生。这种加工诱导转变（PIT）会影响成品的质量。本研究的目的是研究辅料对湿物料中水合物形成动力学的影响。选择无水茶碱作为形成水合物的模型药物化合物，并在配方中使用了两种具有不同吸水特性的辅料，即硅化微晶纤维素（SMCC）和一水乳糖。研究了无水茶碱及其与一水乳糖和SMCC按1:1（w/w）比例混合并加入0.1g/g纯净水的湿法制粒早期阶段。使用近红外光谱监测水状态的变化，并使用X射线粉末衍射（XRPD）验证晶体结构的转变。SMCC通过吸水降低了水合物形成速率，但并未抑制它。结果表明，与仅包含无水茶碱的物料相比，一水乳糖略微提高了水合物形成速率。
