Polymorphs of a crystalline azo-bicyclo (2.2.2) oct-3-yl amine citrate and their pharmaceutical compositions
AssigneePfizer Inc.
InventorsGeorge Joseph Quallich, Lewin Theophilus Wint, Peter Robert Rose, Stephen S. Massett
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Abstract
Two crystalline polymorphic forms of (2-Benzhydryl-1-azo-bicyclo[2.2.2]oct-3-yl)-(5-isopropyl-2-methoxybenzyl)-amine citrate monohydrate (the monohydrates) are Form A and Form B. The pharmaceutical composition containing at least one of these polymorphs has advantageous stability for formulation to treat acute emesis in patient receiving chemotherapy. The administration of this pharmaceutical composition is conventional oral by preferably tablet or capsule and intravenous. A method of making A and B Forms is also disclosed.
Claims19
The crystalline forms of (2-Benzhydryl-1-azo-bicyclo[2.2.2]oct-3-yl)-(5-isopropyl-2-methoxybenzyl)-amine citrate having the formula
- wherein said crystalline form is selected from the group consisting of
- (a) a stable nonhygroscopic citrate anhydrous form exhibiting the X-ray powder diffraction pattern
- Peak No. 1 2 3 4 5 6 7 8 9 D 17.61 10.95 8.78 7.96 7.37 6.80 6.57 5.87 5.46 space
- (b) a citrate monohydrate, Form A polymorph exhibiting the X-ray powder diffraction pattern
- Peak No. 1 2 3 4 5 6 7 8 9 D 17.74 10.93 9.65 8.25 6.71 5.98 5.67 5.45 4.83 space
- and
- (c) A citrate monohydrate, Form B polymorph exhibiting the X-ray powder diffraction pattern
- Peak No. 1 2 3 4 5 6 7 8 9 D 12.3 11.3 6.5 6.9 5.9 4.3 4.1 3.5 3.2 space
A method of making crystalline polymorphic Form A of (2-Benzhydryl-1-azo-bicyclo[2.2.2]oct-3-yl)-(5-isopropyl-2-methoxybenzyl)-amine citrate monohydrate comprising:
- Dissolving anhydrous citrate in isopropyl alcohol and water;
- stirring the mixture overnight at room temperature;
- crystallizing the citrate monohydrate salt and collecting Form A by filtration;
- and drying at about 20 to 80° C. under vacuum.
A method of making crystalline polymorphic Form B of (2-Benzhydryl-1-azo-bicyclo[2.2.2]oct-3-yl)-(5-isopropyl-2-methoxybenzyl)-amine citrate monohydrate comprising:
- Concentrating a solution of the citrate monohydrate in methanol at room temperature for about 48 to 72 hours.
Dependencies are inferred from the claim text.