COMPLEXES OF FULVESTRANT AND ITS DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

摘要

The present invention relates to pharmaceutically acceptable complex formulae comprising complexes of Fulvestrant, or a salt, or derivatives thereof and complexation agents and pharmaceutically acceptable excipients, process for the preparation thereof and pharmaceutical compositions containing them. The complex formulae of the present invention have improved physicochemical properties which makes the compound orally available and makes oral administration of the compound possible in the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy.

主权项

1. A stable complex comprising as active compound chosen from Fulvestrant, its salts or derivatives thereof; and at least one complexation agent chosen from polyvinylcaprolactam-polyvinyl acetate-polyethylene-glycol graft copolymers; poloxamers; polyvinylpyrrolidone; copolymers of vinylpyrrolidone and vinyl-acetate; and poly(maleic acid-co-methyl-vinyl-ether); said complex characterized in that it possesses at least one of the following properties:
a) is instantaneously redispersable in physiological relevant media b) is stable in solid form and in colloid solution and/or dispersion; c) has an apparent solubility in water of at least 1 mg/mL; d) shows X-ray amorphous character in the solid form; e) has a PAMPA permeability of at least 0.6*10−6 cm/s when dispersed in FaSSIF or FeSSIF biorelevant media, which does not decrease in time at least for 1 month; and f) is characterized by infrared (ATR) spectrum having main/characteristic absorption peaks at least at 1412 cm−1, 1197 cm−1 and 1105 cm−1; and a lack of 1611 cm−1 and 1504 cm−1 characteristic absorption peaks.