Process for the production of a crystalline glucagon receptor antagonist compound
View Patent ↗The present invention relates to a process for the production of crystalline particles of a glucagon receptor antagonist compound. The process includes the steps of generating microseeds and subjecting the microseeds to a crystallization process. The resulting crystalline particles have a mean particle size of less than about 100 mm. The present invention also provides for a pharmaceutical composition which includes the crystalline particles produced by the method described herein and a pharmaceutically acceptable carrier.
1. A process for the production of substantially uniform crystalline particles of a compound of the formula I:
comprising:
generating microseeds of the compound of formula I, and
crystallizing the compound of formula I on the microseeds from a suitable solvent or solvent mixture to produce the compound in the form of substantially uniform crystalline particles.
2. A process in accordance with claim 1 wherein the compound of formula is crystallized on the microseeds in the presence of ultrasonic energy.
3. A process in accordance with claim 1 wherein the mean particle size of the resulting crystalline particles is less than 60 μm.
4. A process in accordance with claim 1 wherein the mean size of the micro-seed is approximately 0.5 to 20 μm.
5. A process in accordance with claim 1 wherein the mean size of the micro-seed is approximately 1 to 10 μm.
6. A process in accordance with claim 1 wherein a media mill is utilized to generate the microseeds.
7. A process for the production of substantially uniform crystalline particles of a compound of the formula I:
comprising:
(1) generating a slurry of micro-seeds;
(2) generating a solution of the compound of formula I to be crystallized in a suitable solvent;
(3) combining the product of step (1) and the product of step (2) in the presence of ultrasonic energy, and
(4) adding a suitable anti-solvent to cause crystallization of the compound of formula I.
8. A process in accordance with claim 7 wherein a recycle loop is utilized during the crystallization process.
9. A process in accordance with claim 7 wherein a supplemental energy device is utilized during the crystallization process.
10. A process in accordance with claim 9 wherein the supplemental energy device is a mixing tee, a mixing elbow, a static mixer, a sonicator, or a rotor stator homogenizer.
11. A process in accordance with claim 9 wherein the supplemental energy device is placed in a recycle loop.
12. A process in accordance with claim 11 wherein the crystallization process further comprises adding the micro-seeds, a batch solution, a reagent solution, or an antisolvent into a recycle loop or a region of high mixing intensity.
13. A process in accordance with claim 7 wherein the slurry of the micro-seeds and the solution of the compound of formula I are rapidly micro-mixed when they are combined.
14. A process in accordance with claim 1 wherein the resulting crystalline particles have a crystalline form that corresponds to the form of the micro-seeds.