Steroid hormone products and methods for preparing them

Abstract

The present invention relates to steroid hormone products, such as oral contraceptive products, including at least one steroid active ingredient mixed with an excipient and having improved dissolution and release rate properties. The invention further relates to methods for making such steroid hormone products, wherein a mixture of the hormone and the excipient is subjected to sufficient mechanical energy to form a powder blend wherein the hormone is stabilized by the excipient in substantially non-crystalline form.

1 . A method of preparing a steroid hormone product having improved dissolution and release rate properties, said product comprising norgestimate in admixture with an excipient, wherein substantially all of said norgestimate is in non-crystalline form and wherein said excipient stabilizes said norgestimate in its non-crystalline form, said method comprising the steps of:
 preparing a mixture comprising at least norgestimate and at least one excipient;   imparting to said mixture sufficient mechanical energy to yield an excipient/norgestimate powder blend wherein the norgestimate is stabilized by said excipient in substantially non-crystalline form; and   forming said product from the powder blend.   
     
     
         2 . The method of  claim 1 , wherein the step of preparing the mixture includes the steps of:
 preparing a solution of the norgestimate in a suitable solvent;   uniformly mixing the solution with the excipient; and   removing the solvent.   
     
     
         3 . The method of  claim 1 , wherein at least about 0.1 hp-min/kg of mechanical energy is imparted to the mixture to form the powder blend. 
     
     
         4 . The method of  claim 1 , wherein the step of imparting mechanical energy to the mixture is further characterized in that the mixture is subjected to high energy blending. 
     
     
         5 . The method of  claim 1 , wherein the mixture comprises a norgestimate/excipient ratio of from about 1/1 to about 1/10. 
     
     
         6 . The method of  claim 1 , wherein the excipient is selected from the group consisting of dextrose, fructose, sorbitol, xylitol, sucrose, lactose, mannitol, dextrate, cellulose, starch and mixtures thereof. 
     
     
         7 . The method of  claim 6 , wherein the excipient is lactose. 
     
     
         8 . The method of  claim 1 , wherein the steroid hormone product comprises norgestimate and an estrogen. 
     
     
         9 . The method of  claim 8 , wherein the estrogen is ethinyl estradiol. 
     
     
         10 . The method of  claim 8  wherein the product is an oral contraceptive product comprising from about 10 μg to about 50 μg of an estrogen and/or from about 50 μg to about 300 μg of norgestimate. 
     
     
         11 . The method of  claim 10 , wherein the estrogen is ethinyl estradiol.