DETAILED DESCRIPTION The present invention provides a process for maintaining uniformity and potency during the manufacture of a pharmaceutical composition containing a highly potent active ingredient.
The process includes a means for reducing the loss of active ingredients that adhere to the metal surfaces of equipment during the manufacturing process of a pharmaceutical composition or medicament.
Active ingredients of particular interest are SERM compounds of Formula (I) below: ##STR1## where E and B are independently selected from CH and N; R1 is hydrogen, hydroxy, fluoro or chloro; and G is ##STR2## a prodrug thereof, or a pharmaceutically acceptable salt, hydrate or solvate of the compound or the prodrug.
Preferred compounds include cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-naphthalen-2-ol; (-)-cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-naphthalen-2-ol; cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-naphthalen-2-ol; cis-1-[6′-pyrrolodinoethoxy-3′-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrahydrohaphthalen-1-(4′-pyrrolidinoethoxyphenyl)-2-(4"-fluorophenyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline; cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-naphthalen-2-ol; and 1-(4′-pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoquinoline.
A more preferred compound is cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol; a prodrug thereof, or a pharmaceutically acceptable salt, hydrate or solvate of the compound or the prodrug.
The compounds of Formula (I) are very potent compounds thus requiring special handling to reduce operator exposure during the manufacturing process.
In addition, the compounds of Formula (I) may be sensitive to oxidation which may limit or preclude the use of liquids and materials containing peroxide contaminants (e.
g.
, polyethylene glycols) during drug product manufacture
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