片剂薄膜包衣过程激光共聚焦成像及近红外光谱建模分析

Quality Assessment of Film Coating Tablet Samples Using Confocal Laser Scanning Microscopy Imaging and Near Infrared Spectroscopy

关键词:  薄膜包衣  近红外光谱  激光共聚焦  片剂  偏最小二乘回归

Key words:  film coating  near infrared spectroscopy  confocal laser scanning microscopy  tablets  partial least squares

摘要:

目的 研究薄膜包衣的微观成膜过程，实现对包衣质量无损检测模型的构建。方法 采用聚乙烯吡咯烷酮为包衣材料对微晶纤维素片进行包衣，在包衣材料中加入罗丹明为示踪剂。测定包衣过程不同时间包衣增重和衣膜厚度，并通过激光共聚焦显微镜成像系统和近红外光谱技术分别测定包衣片衣膜的微观结构和宏观图谱，最后采用化学计量学的方法关联近红外图谱与衣膜质量，构建包衣过程的控制模型。结果 衣膜在片芯表面呈现非均匀分布，先分布于片芯两侧表面，后分布于片芯曲面，这种差异随包衣的进行逐渐降低，且在衣膜表面存有微小的孔隙结构。多元散色矫正预处理后的近红外光谱图形能够构建包衣质量的精确控制和预测模型。结论 激光共聚焦成像及近红外光谱技术能够分别从微观和宏观角度增进对薄膜包衣过程的理解和控制，有助于促进薄膜包衣技术的进一步开发利用。

Abstract:

OBJECTIVE To study the microscopic film-forming process of film coating, and realize the construction of non-destructive testing model for coating quality. METHODS The microcrystalline cellulose tablets were coated with polyvinylpyrrolidone as a coating shell material, and rhodamine was added as a tracer in the coating shell material. The coating weight gain and film thickness of coated tablets were measured at different coating times, and the microstructure and macroscopic profiles of the coated film were determined by confocal laser scanning microscopy and near infrared spectroscopy, respectively. Then chemometrics method was utilized to correlate the near infrared spectra with the film quality, and finally the control models for the coating process was constructed. RESULTS The film was inhomogeneously distributed on the surface of the tablets. It was primarily disturbed on both sides of the tablet and subsequently distributed on the curved portions. This difference gradually decreased with the progress of the coating. In addition, the microstructure indicated that there exists microporous structure on the surface of the film. Near infrared spectra after multiple scattering correction pretreatment could accurately control and predict the coating quality. CONCLUSION Confocal laser scanning microscopy and near infrared spectroscopy can enhance the understanding and control of film coating from microscopic and macroscopic aspects, and help to develop and utilize the film coating technology.