Physicochemical Characterization and Reverse Engineering of Reference Market Product for Generic Formulation Development

Abstract

The present study aimed to carry out reverse engineering of reference innovator product (Xarelto® 20 mg film-coated tablets) to decode the critical scientific information that is needed for successfully develop a stable and bio-equivalent generic formulation of rivaroxaban 20 mg film-coated tablets. The innovator product characterization was done followed by deformulation of the reference product (Xarelto® 20 mg film-coated tablets) to quantity critical excipients to decode the innovator product’s quantitative composition and to identify the manufacturing process used to manufacture the innovator product. The particle size distribution and particle size distribution of rivaroxaban API used in the innovator product were performed using hot-stage microscopy. The polymorphic form of rivaroxaban API used was identified using DSC and XRD methods. Visual, tactile and microscopic evaluation of granules obtained from crushed tablets of the innovator product revealed that the granulation process was used in the manufacturing of the innovator product. It was further concluded that the manufacturing process is wet granulation process due to the presence of organic solvent in the innovator core tablet. Physical evaluation was done to know the tablet weight, shape, size, coating appearance, tablet hardness and disintegration time. Chemical analysis was performed to record the drug content, percentage impurity and dissolution profile. The decoded information can serve as a reference for a faster and bioequivalent generic formulation development with reduced cost, time, effort, and a higher success rate