| 主权项 |
1. A process for the preparation of anhydrous tiotropium bromide having an XRPD pattern comprising at least three peaks selected from peaks with 2θ angles of about 8.49, 11.38, 13.58, 14.24, 14.74, 16.01, 17.03, 17.93, 18.60, 19.15, 21.80, 22.62, 22.92, 23.29, 25.29, 25.57, 26.23, 27.29, 28.07, 28.61, 30.24 and 31.83±0.2 degrees, wherein the anhydrous tiotropium bromide further comprises:
(i) an XRPD spectrum substantially as shown in FIG. 1; and/or (ii) a DSC spectrum with endothermic peaks at about 208° C.+2° C. and about 221° C.+2° C.; and/or (iii) a DSC spectrum substantially as shown in FIG. 2; and/or (iv) a TGA spectrum substantially as shown in FIG. 3;wherein the process comprises the steps of:
(a) providing a solution of scopine di-(2-thienyl)glycolate and a first organic solvent; (b) adding a solution of methyl bromide in a second organic solvent to the mixture from step (a) or vice versa; (c) isolating anhydrous tiotropium bromide from the mixture obtained in step (b); and (d) drying the isolated anhydrous tiotropium bromide. |
