2.

Synthesis and characterization of related substances and metabolite of tadalafil, a PDE-5 inhibitor

Goverdhan Gilla, Raghupathi Reddy Anumula, Sampath Aalla, Himabindu Vurimidi and Mahesh Reddy Ghanta

Research and Development, Integrated Product Development, Dr. Reddy’s Laboratories Ltd, Survey No`s 42, 45, 46 &54, Bachupally, Qutubullapur, Ranga Reddy District- 500 072, Andhra Pradesh, India

Institute of Science and Technology, Center for Environmental Science, J.N.T.University, Kukatpally, Hyderabad- 500 072, Andhra Pradesh, India.

Macleods Pharmaceuticals, Andheri East, Mumbai-400059, Maharashtra, India.

Abstract: Tadalafil (Cialis) is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type-5 (PDE-5) and it is administered orally for the treatment of erectile dysfunction (ED). Two synthetic schemes were evaluated to study the impurity profile of tadalafil. Six impurities were detected in the bulk substance (prepared by two methods) at a level of 0.1-0.15%. Identification, synthesis, characterization of impurities (related substances) and metabolite and origin of their formation is described .

Keywords: Tadalafil; PDE-5 inhibitor; metabolite; related substances; two synthetic schemes.