Raman Spectroscopy Study In Polymorphs Analysis And Component Distribution And Consistency Evaluation Of Solid Oral Preparation

As different polymorphs of solid oral preparation show significant difference in clinical effect, in this research, crystal type identification, crystal stability study, components distribution, in vitro dissolution and packaging material identification of clopidogrel bisulphate tablets (CBT) and carbamazepine tablets were analyzed as follows:(1) By using Laser Micro-Raman Spectrometer (LMRS) and Cluster Analysis (CA),8batches of CBT from domestic manufacturers were identified as crystal Ⅰ, while3batches from foreign manufacturers were identified as crystal Ⅱ. The counterfeit and negative samples could be distinguished quickly and the crystal type of CBT could be identified correctly by a new identification model established by qualitative model method. The model showed high sensitivity and specificity, good negative prediction and detection efficiency. (2) The prepared crystal forms Ⅰ, Ⅱ, ⅢⅢ, Ⅳ of carbamazepine were characterized by XRD and Raman spectroscopy and then identified by CA, in which4batches of carbamazepine tablets were type Ⅲ. Another identification model was established by qualitative model method to distinguish negative samples and identify crystal types of carbamazepine tablets.(3) Transformations between different crystal types under different environmental conditions, which were with high temperature, high humidity and light condition, of crystal type Ⅰ and Ⅱ of clopidogrel bisulphate (CB) and crystal type Ⅰ, Ⅱ, Ⅲ and Ⅳ of carbamazepine were investigated by LMRS to determine suitable environment for each crystal type to remain stable. The degradation impurities under each environmental condition were analyzed by HPLC.(4) Components distribution of domestic and foreign CBT was analyzed by drawing the Raman spectrum of the tablet surface with DCLS, PCA and MCR-ALS methods to process the collected spectrum pretreated by appropriate methods. The number of components resulted from MCR-ALS analysis method was consistent with the result from PCA, and the Raman reference spectrum of each component could be generated.(5)The consistency evaluation scheme of CBT was determined by testing the solubility of CB and drawing dissolution curves of CBT in different buffers. Optical fiber dissolution instrument was used to compare the in vitro release consistency of generic and original CBT by comparing the similarity factor (f2) of dissolution curves in five dissolution medium. As a result, the dissolution of generic drugs were not similar to the original drugs in pH2.0hydrochloric acid buffer solution, pH4.0acetate buffer solution and water.(6) A LMRS consistency model of the black words on the aluminum plate of Sanofi company was created by collecting different colors of inks on the package of CBT products to quickly screen out the counterfeit Sanofi production which would show difference Raman spectrum in the aluminum plate although with the same package.