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Rivaroxaban is a pure (S)-enantiomer. It is an odorless, non-hygroscopic, and white to yellowish powder. Rivaroxaban is only slightly soluble in organic solvents (e.g., acetone, polyethylene glycol 400) and is practically insoluble in water and aqueous media. The chemical name of Rivaroxaban is 5-Chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4- morpholinyl) phenyl]-1,3-oxzolidin-5-yl}methyl)-2-thiophene-carboxamide.The 1,3-oxazolidin ring system has 5  chiral carbon-atom with (S) configuration. Single-crystal x-ray structural analysis confirms the S configuration of the molecule. Rivaroxaban is tested for polymorphism and pseudo-polymorphism according to the ICH Q6A guideline.

 Rivaroxaban crystallizes in three polymorphs. Polymorph I is the thermodynamically stable one, used in tablet formulations during clinical development, and used in the commercial product. The identity of polymorph I is routinely controlled by Raman spectroscopy.

 

Synthesis

v  Rivaroxaban is synthesized using a five-step synthetic process using 4-(4-nitrophenyl)-3- morpholinone as a starting material. Three key intermediates must be synthesized, which are then used in the reaction to form the active substance.

v  Controled quality of the starting materials, solvents and reagents, and isolated intermediates are used.

v  Eighteen process impurities originating from the starting materials and the synthetic process have been identified. The Structure of each impurity is based on spectral analysis data (NMR and spectrometry).

v  The solvents used in the synthesis should be efficiently removed during the purification and drying operations to get good yield Target product.

 

Stability

 Stability data is tested for three batches of the active substance stored at 25 °C / 60 % RH for 18 months and at 40 °C /75 % RH for six months. The parameters studied were appearance (material, colour), colour of solution, polymorphism, particle size, enantiomeric purity, organic impurities, assay and water content using the analytical test methods.

 

Uses of Rivaroxaban in Medication:

·         Rivaroxaban is used to treat deep vein thrombosis (DVT; a blood clot, usually in the leg) and pulmonary embolism (PE; a blood clot in the lung) in adults.

·         It is also used to help prevent strokes or serious blood clots in adults who have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body, and possibly causing strokes) that is not caused by heart valve disease.

·         Rivaroxaban is also used to prevent DVT and PE in adults who are having hip replacement or knee replacement surgery or in people who are hospitalized for serious illnesses and are at risk of developing a clot due to decreased ability to move around or other risk factors.

·         It is also used along with aspirin to lower the risk of a heart attack, stroke, or death in adults with coronary artery disease (narrowing of the blood vessels that supply blood to the heart) or peripheral arterial disease (poor circulation in the blood vessels that supply blood to the arms and legs).

·          Rivaroxaban is also used to treat and prevent DVT and PE from happening again in children and certain infants who have received at least 5 days of initial anticoagulation (blood thinner) treatment. It is also used to prevent DVT and PE after heart surgery in children 2 years of age or older who have congenital heart disease (abnormality in the heart that develops before birth).

·         Rivaroxaban is in a class of medications called factor Xa inhibitors. It works by blocking the action of a certain natural substance that helps blood clots to form.

 

Rivaroxaban-d4 

Rivaroxaban-d4 is used as an internal standard for the quantification of rivaroxaban by GC- or LC-MS. Rivaroxaban is an orally active, direct inhibitor of Factor Xa (Ki = 0.4 nM), which is a crucial component of the intrinsic and extrinsic pathways of the blood coagulation cascade. It demonstrates >10,000-fold greater selectivity for Factor Xa compared to other related serine proteases. In various animal arterial and venous thrombosis models, rivaroxaban is reported to inhibit thrombin formation without prolonging bleeding time.

Formulations containing rivaroxaban have been used as an anticoagulant in the prevention of stroke and the treatment of venous thromboembolisms.



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