Optical Sciences Group, Faculty of Science and Technology, MESA+ Institute of Nanotechnology, University of Twente, Enschede, The Netherlands.
Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):1141-7. doi: 10.1016/j.ejpb.2013.08.012. Epub 2013 Aug 28.
The solid-state form of an active pharmaceutical ingredient (API) in an oral dosage form plays an important role in determining the dissolution rate of the API. As the solid-state form can change during dissolution, there is a need to monitor the oral dosage form during dissolution testing. Coherent anti-Stokes Raman scattering (CARS) microscopy provides rapid, spectrally selective imaging to monitor the oral dosage form during dissolution. In this study, in situ CARS microscopy was combined with inline UV absorption spectroscopy to monitor the solid-state change in oral dosage forms containing theophylline anhydrate undergoing dissolution and to correlate the solid-state change with a change in dissolution rate. The results from in situ CARS microscopy showed that theophylline anhydrate converted to theophylline monohydrate during dissolution resulting in a reduction in the dissolution rate. The addition of methyl cellulose to the dissolution medium was found to delay the theophylline monohydrate growth and changed the morphology of the monohydrate. The net effect was an increased dissolution rate for theophylline anhydrate. Our results show that in situ CARS microscopy combined with inline UV absorption spectroscopy is capable of monitoring oral dosage forms undergoing dissolution and correlating changes in solid-state form with changes in dissolution rate.
口服剂型中活性药物成分 (API) 的固态形式在确定 API 的溶解速率方面起着重要作用。由于固态形式在溶解过程中会发生变化，因此需要在溶解测试过程中监测口服剂型。相干反斯托克斯拉曼散射 (CARS) 显微镜提供快速、光谱选择性成像，可在溶解过程中监测口服剂型。在这项研究中，原位 CARS 显微镜与在线紫外吸收光谱相结合，监测含有无水茶碱的口服剂型在溶解过程中的固态变化，并将固态变化与溶解速率的变化相关联。原位 CARS 显微镜的结果表明，无水茶碱在溶解过程中转化为一水茶碱，导致溶解速率降低。向溶解介质中添加甲基纤维素被发现可以延迟一水茶碱的生长并改变一水茶碱的形态。最终的效果是无水茶碱的溶解速率增加。我们的结果表明，原位 CARS 显微镜与在线紫外吸收光谱相结合能够监测溶解过程中的口服剂型，并将固态形式的变化与溶解速率的变化相关联。
