Salts of the CGRP antagonist BIBN4096 and inhalable powdered medicaments containing them

A process for preparing an acid addition salt of the compound 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine, which is also known as BIBN4096,and which has the formula

• 3
• (a) dissolving 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine (the base) in a solvent, selected from the group consisting of water and an aqueous buffer system with a pH between 4 and 8,
• (b) combining the solution thus prepared with an excess of the acid, and
• (c) removing the solvent.

A process for preparing an inhalation powder, comprising the steps of

• (a) dissolving a pharmaceutically acceptable acid addition salt of 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1 H)-oxoquinazolin-3-yl)-1 -piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine in water, or 1 -[N2[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine in an aqueous system containing an excess of a mineral acid or an organic acid, depending, whereby it is converted into a corresponding pharmaceutically acceptable salt,
• (b) spraying the resulting solution of the salt so as to obtain a spray mist with a droplet size having the characteristic value X50 in the range from 1.5 to 30 μm,
• (c) drying the spray mist thus obtained by means of a drying gas, while applying the following parameters:
• (1) an inlet temperature of the drying gas of 100° C. to 350° C.,
• (2) an outlet temperature of the drying gas of 40° C. to 120° C.,
• (3) a volumetric flow of the spray gas of 1 Nm3/h to 15 Nm3/h, and
• (4) a volumetric flow of the drying gas of 15 Nm3/h to 1500 Nm3/h, preferably 15 Nm3/h to 150 Nm3/h, and
• (d) separating the dried solid fraction from the drying gas current.