Comparative Characterization of Reference Market Product and Generic Product Developed using Reverse Engineering Methodology

Abstract

The present study is a comparative analysis between the reference market product, Xarelto® 20 mg film-coated tablets, and a generic product developed using reverse engineering methodology, employing low-shear ethanolic granulation. The primary objective in formulating and optimizing this generic product was to attain a formulation that exhibits both physical and chemical stability, closely resembling the innovator or market reference drug product. Both reference and generic products were evaluated using FTIR, TGA, DSC, XRD, SEM, EDX/EDS, Raman mapping, Raman imaging and contact angle measurement studies and were compared. Similar characteristic peaks were observed in the IR spectra of the generic product (RX-LS [AH]) to that of the reference product. Similar crystallinity was detected between reference and generic products. The TG-DSC analysis confirmed the presence of a similar endothermic peak of the generic product to that of the reference product. SEM images showed the presence of deformed granules in both, generic and reference products due to the compression force during tablet production. The specific and major elements present in both samples were C, N, O, Na, Mg, S and Cl. The API and excipient distribution within the reference product and the generic product is closely similar confirmed through the Raman study. Test (θ = 17.3) and reference products (θ = 17.9) showed contact angles around 17 degrees, it indicates that both products have similar wettability capacity, in other words, similar solubility and dissolution behavior. The current study demonstrated the excellent similarity of generic Rivaroxaban 20 mg film-coated tablets with reference products. The exactly similar characteristics of generic products will definitely boost confidence of successful bioequivalence studies and reduce developmental cost and time as there is no a chance of product failure which will lead to redevelopment.