Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark; Bioneer: Farma, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
J Pharm Biomed Anal. 2021 Feb 5;194:113789. doi: 10.1016/j.jpba.2020.113789. Epub 2020 Nov 25.
The purpose of this study was to investigate whole-dosage form UV-vis imaging as a potential tool for functional characterization of excipients used in solid oral dosage forms. To this end, tablets (average mass 260.0 mg, 224.5 mg and 222.1 mg) containing theophylline anhydrate (20 % w/w), 1% (w/w) magnesium stearate, and 79 % (w/w) of either microcrystalline cellulose (MCC, Avicel PH 101) or hydroxypropyl methylcellulose (HPMC, Methocel K15 M or K100 M) were prepared as model systems. Drug liberation from tablets was studied in 0.01 M HCl at 37 °C using a Sirius SDi2 equipped with a USP IV type flow cell comprising a UV-vis imaging detector operating at 255 nm and 520 nm. The effluent from the flow cell was passed through a downstream spectrophotometer, and UV-vis spectra in the wavelength range 200-800 nm were recorded every 2 min. The erosion and swelling behavior of the MCC tablets and HPMC K15 M and K100 M tablets were visualized in real time. The swelling of HPMC K15 M and K100 M containing tablets was assessed quantitatively as changes in tablet diameter measured at 520 nm, and was clearly distinguished from the swelling of the MCC tablets. Namely, an increment of 2.5 mm in diameter was determined for the HPMC tablets while the MCC tablets increased by 0.5-1 mm in diameter. Gel layers of variable thickness were observed only for the HPMC K15 M and K100 M tablets. In addition, a relatively high initial liberation rate of theophylline was found for the MCC tablets as compared to the HPMC tablets. UV-vis imaging revealed features of liberation not revealed by simply measuring drug concentration in the dissolution media or by visual assessment. It may be sufficiently sensitive to be further developed for functional characterization of excipients and provide insights into drug-excipient interactions likely to be useful in formulation development.
本研究旨在探讨全剂量形式的紫外可见成像作为一种潜在的工具，用于对固体制剂中辅料的功能特性进行表征。为此，制备了含有茶碱无水物（20%w/w）、1%（w/w）硬脂酸镁和 79%（w/w）微晶纤维素（MCC，Avicel PH 101）或羟丙基甲基纤维素（HPMC，Methocel K15 M 或 K100 M）的片剂模型系统，片剂平均质量为 260.0mg、224.5mg 和 222.1mg。采用 Sirius SDi2 型仪器，配备 USP IV 型流动池，在 37°C、0.01 M HCl 中对片剂的药物释放进行了研究。流动池内装有紫外可见成像检测器，检测波长为 255nm 和 520nm。从流动池流出的溶液通过下游分光光度计，每隔 2min 记录 200-800nm 波长范围内的紫外可见光谱。实时观察 MCC 片剂和 HPMC K15 M 和 K100 M 片剂的溶蚀和溶胀行为。通过在 520nm 处测量片剂直径的变化，定量评估 HPMC K15 M 和 K100 M 片剂的溶胀情况，这与 MCC 片剂的溶胀明显不同。结果表明，HPMC 片剂的直径增加了 2.5mm，而 MCC 片剂的直径增加了 0.5-1mm。仅观察到 HPMC K15 M 和 K100 M 片剂存在厚度可变的凝胶层。此外，与 HPMC 片剂相比，MCC 片剂的茶碱初始释放速率较高。紫外可见成像技术揭示了药物释放的特征，这些特征无法通过简单地测量溶解介质中的药物浓度或通过视觉评估来揭示。它可能具有足够的敏感性，可以进一步开发用于辅料的功能特性表征，并提供药物-辅料相互作用的见解，这可能对制剂开发有用。
