Entecavir: stability and drug-excipient compatibility

Abstract

Abstract Entecavir is an inhibitor of hepatitis B virus (HBV) DNA synthesis that has been widely prescribed in the treatment of chronic infections caused by the virus. Production of generic ETV drugs is an ongoing global endeavor, with particular significance for developing countries that rely on importing the expensive reference drug. ETV-excipient compatibility studies were conducted with the declared inputs in solid pharmaceutical formulations on the market through thermal analysis and HPLC techniques. Thermal analyses by TGA and DTA indicated compatibility of entecavir with the excipients microcrystalline cellulose, crospovidone, titanium dioxide, magnesium stearate, hypromellose, polyethylene glycol and povidone; this was confirmed via HPLC. Lactose monohydrate proved to be incompatible with ETV in thermal and chromatographic assays. The thermal analysis of marketed solid dosage forms revealed a predominance of the lactose monohydrate profile at the expense of ETV and other inputs in the TGA and DTA curves, due to its high content in the formulations; this makes the evidence of ETV-lactose chemical interaction even more important. Compatibility tests by HPLC showed no chemical interaction of ETV with the excipient mannitol, a soluble diluent proposed as a replacement for lactose monohydrate, with the same function in the formulation.