Sarraguça Mafalda Cruz, Matias Rita, Figueiredo Raquel, Ribeiro Paulo Roberto S, Martins Ana Teixeira, Lopes João Almeida
LAQV/REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Centro de Ciências Sociais, Saúde e Tecnologia (CCSST), Universidade Federal do Maranhão (UFMA), CP: 65.900-410, Imperatriz, MA, Brazil.
Int J Pharm. 2016 Nov 20;513(1-2):1-7. doi: 10.1016/j.ijpharm.2016.09.010. Epub 2016 Sep 4.
Dissolution tests can be used to demonstrate suitable in vivo drug release through in vivo/in vitro correlations. This work explores the possibility of using near infrared spectroscopy (NIRS) to monitor in-situ dissolution tests. It aims at expanding surrogate methods in quality control of drug products. Laboratory designed tablets of an immediate-release formulation containing folic acid and four excipients were used as case study. The dissolution tests were performed on a 1L vessel filled with 500ml of Milli-Q water with a rotating paddle apparatus (apparatus 2, Ph. Eur.) at 50rpm and 37±0.5°C. Near infrared (NIR) spectra were acquired in-situ with a transflectance probe connected to a Fourier-transform near infrared spectrometer. NIR spectra were regressed against folic acid concentration by partial least squares (PLS) regression. Folic acid concentrations during dissolution tests were obtained by periodically sampling the dissolution vessel and resourcing to an UV method. The proposed real-time NIR method was tested on a validation run yielding a root mean squared error of 0.25μgml (0.16μgml for the calibration runs) and a R of 0.93 (0.95 for the calibration runs). The results suggest that NIRS is a suitable analytical technique for monitoring in-situ dissolution tests.
溶出度试验可用于通过体内/体外相关性来证明合适的体内药物释放情况。本研究探讨了使用近红外光谱（NIRS）监测原位溶出度试验的可能性。其目的是扩展药品质量控制中的替代方法。以含有叶酸和四种辅料的速释制剂的实验室设计片剂作为案例研究。溶出度试验在装有500ml超纯水的1L容器中进行，使用旋转桨法（欧洲药典装置2），转速为50rpm，温度为37±0.5°C。通过连接到傅里叶变换近红外光谱仪的漫反射探头原位采集近红外（NIR）光谱。通过偏最小二乘法（PLS）回归将近红外光谱与叶酸浓度进行回归分析。溶出度试验期间的叶酸浓度通过定期从溶出容器中取样并采用紫外法获得。所提出的实时近红外方法在验证试验中进行了测试，得到的均方根误差为0.25μg/ml（校准试验为0.16μg/ml），相关系数R为0.93（校准试验为0.95）。结果表明，近红外光谱是监测原位溶出度试验的合适分析技术。
