Claims
- 1. A method for preparing a crystalline form of estradiol characterized by possessing at least one diffraction peak having a 2.theta. angle of 11.2.degree..+-.0.2.degree., 12.7.degree..+-.0.2.degree., 17.4.degree..+-.0.2.degree. or 19.6.degree..+-.0.2.degree., said method comprising the steps of:
- a) preparing a supersaturated suspension of estradiol hemihydrate crystals in an adhesive and solvent;
- b) removing the solvent;
- c) heating the suspension to a temperature sufficient to dissolve the estradiol hemihydrate crystals in the adhesive; and
- d) transferring the suspension to conditions wherein the supersaturation ratio is greater than or equal to about 12.
- 2. A method for preparing a crystalline form of of estradiol characterized by possessing at least one diffraction peak having a 2.theta. angle of 11.2.degree..+-.0.2.degree., 12.7.degree..+-.0.2.degree., 17.4.degree..+-.0.2.degree. or 19.6.degree..+-.0.2.degree., said method comprising the steps of:
- a) preparing a supersaturated suspension of estradiol hemihydrate crystals in an adhesive and solvent;
- b) removing the solvent;
- c) heating the suspension of to a temperature sufficient to dissolve the estradiol hemihydrate crystals in the adhesive; and
- d) transferring the suspension to conditions of approximately 32.degree. C. and 80% relative humidity.
- 3. A method for preparing a crystalline form of of estradiol characterized by possessing at least one diffraction peak having a 2.theta. angle of 11.2.degree..+-.0.2.degree., 12.7.degree..+-.0.2.degree., 17.4.degree..+-.0.2.degree. or 19.6.degree..+-.0.2.degree. from micronized estradiol hemihydrate (E2-HH) crystals said method comprising the steps of:
- a.) preparing a sample of pure micronized E2-HH in an sealed container in the absence of extraneous water;
- b.) heating the sample to the melting temperature of the micronized E2-HH and
- c.) cooling the sample at a controlled rate so as to form Crystal X.
- 4. The method of claim 1, further comprising the step of e) incorporating the suspension into a pharmaceutical formulation.
- 5. The method of claim 4, wherein the pharmaceutical formulation comprises a transdermal drug delivery device.
- 6. The method of claim 5 wherein the pharmaceutical formulation further comprises a skin permeation enhancer.
- 7. The method of claim 5, wherein the pharmaceutical formulation further comprises a progestin.
- 8. The method of claim 1, wherein the adhesive is chosen from the group consisting of acrylates, silicones, and polyisobutylenes.
- 9. The method of claim 2, further comprising the step of e) incorporating the suspension into a pharmaceutical formulation.
- 10. The method of claim 9 wherein the pharmaceutical formulation comprises a transdermal drug delivery device.
- 11. The method of claim 10, wherein the pharmaceutical formulation further comprises a skin permeation enhancer.
- 12. The method of claim 10, wherein the pharmaceutical formulation further comprises a progestin.
- 13. The method of claim 2, wherein the adhesive is chosen from the group consisting of acrylates, silicones, and polyisobutylenes.
- 14. The method of claim 3 wherein the controlled rate of cooling is approximately 5.degree. C. per minute.
- 15. The method of claim 3, further comprising the step of d) incorporating the sample into a pharmaceutical formulation.
- 16. The method of claim 15 wherein the pharmaceutical formulation further comprises a pharmaceutical excipient.
- 17. The method of claim 16, wherein the pharmaceutical formulation comprises tablets.
- 18. The method of claim 15, wherein the pharmaceutical formulation further comprises a progestin.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority to U.S. provisional application Ser. No. 60/030,524 filed Nov. 12, 1996, from which application priority is claimed pursuant to 35 U.S.C. .sctn. 120.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5827245 |
Horstmann et al. |
Oct 1998 |
|