Solid state 13C NMR spectroscopy as a tool for identification of counterfeit Viagra tablets and guide for develop new identification approach of falsified product.

Counterfeit drugs are a global problem that is directly related to the safety and effectiveness of pharmacotherapy. The black market for counterfeit products is constantly growing and related to the wide availability through online shopping. Therefore, there is a constant need to develop analytical methods that would allow for the unambiguous identification of counterfeit products from the original ones. One of such techniques is solid-state NMR spectroscopy, which allows for direct registration and analysis of spectra of multicomponent solid forms of pharmaceutical formulations. The paper explores the possibility of using this technique in the identification of counterfeit Viagra tablets. In this study, solid-state NMR has been used to detect the non-pharmacopoeial cellulose present in the samples of counterfeit Viagra tablets. Besides, the NMR results allowed to develop a rapid dying technique that can be used to distinguish between the counterfeit and original drug. It has been shown that solid-state NMR spectroscopy allows for numerous analyses such as identification of counterfeit products, assessment of the composition of analyte, estimation of qualitative differences between the original and falsified product, and the development of simple analytical methods based on tablets composition differences.

Comparison of the analytical methods (solid state NMR, FT-IR, PXRD) in the analysis of the solid drug forms with low concentration of an active ingredient - 17-ß-estradiol case.

The application of various techniques (FT-IR, PXRD, ssNMR) in the analysis of solid dosage forms with low concentration of an API (17-ß-estradiol hemihydrate, EBHH) was tested. PXRD analysis of Estrofem Mite tablets (EMT) confirmed the presence of the main crystalline excipient, α-lactose monohydrate. In the PXRD pattern of EMT the strong background from polycrystalline excipients, i.e. hydroxypropylmethylcellulose and corn starch was observed. FT-IR spectra were characterized by the broad peaks in the 3000-3600cm-1 region of the OH stretching modes coming from multiple hydrogen bonds that are present in the structures of the excipients (α-lactose monohydrate, corn starch) and API. The only technique which unambiguously confirmed the presence of an API in the EMT was solid state NMR. Despite the tabletting process each of the EMT component retained its characteristic features like relaxation time and T1ρI. Due to the possibility of the manipulation in the experimental registration parameters like recycle delay (RD), evolution time (τ) and contact time (CT) it was possible to perform multiple experiments on the same sample of EMT. The most valuable were the inversion recovery CP experiments in which, by setting the proper values of τ, it was possible to selectively observe the signals of the chosen component of the drug formulation. In this study the great potential of solid state NMR in the analysis of solid dosage forms, as the unique technique that combines the possibility of selective observation of the chosen signals with the non destructive character that enables further analysis of the same sample, was confirmed.