Compositions of GnRH related compounds and processes of preparation

Abstract

The present invention provides compositions of GnRH related compounds that are suitable for oral administration, injectable administration and other forms of administration wherein the gelling characteristics of the composition are a factor. The compositions of the present invention comprise a therapeutically effective amount of one or more GnRH related compound, and a sufficient amount of at least one anti-gelling agents to reduce the gelation of the GnRH related compound. The present invention also provides processes for preparation of a composition of one or more GnRH related compound, wherein the process comprises mixing the GnRH related compound with one or more anti-gelling agents, wherein the anti-gelling agent comprises a medium chain fatty acid salt, or an ester, an ether, or a derivative of a medium chain fatty acid and has a carbon chain length of from about 4 to about 20 carbon atoms or is a surface active agent.

1 - 45 . (canceled) 
     
     
         46 . A solid oral dosage form comprising a therapeutically effective amount of one or more GnRH agonists, and a sufficient amount of at least one anti-gelling agent to reduce the gelation of the GnRH agonist, wherein at least one anti-gelling agent is a medium chain fatty acid salt and has a carbon chain length of from about 8 to about 14 carbon atoms. 
     
     
         47 . The solid oral dosage form of  claim 46 , wherein the solid oral dosage form is prepared by mixing the one or more GnRH agonists with the at least one anti-gelling agent;
 wherein the final step of the preparation of the GnRH agonist is conducted in the presence of a co-solvent system in a manner such that the gelation of the GnRH agonist is reduced.   
     
     
         48 . The solid oral dosage form of  claim 47 , wherein the co-solvent system comprises water and at least one water-miscible solvent. 
     
     
         49 . The solid oral dosage form of  claim 48 , wherein the water-miscible solvent selected from the group consisting of methanol, ethanol, iso-propanol, tert-butanol, acetonitrile and methylene chloride. 
     
     
         50 . The solid oral dosage form of  claim 46 , wherein the gelation of at least 90% of the GnRH agonist is inhibited. 
     
     
         51 . The solid oral dosage form of  claim 46 , wherein the anti-gelling agent is selected from the group consisting of sodium caprylate, sodium caprate and sodium laurate. 
     
     
         52 . The solid oral dosage form of  claim 46 , further comprising a rate-controlling polymer. 
     
     
         53 . The solid oral dosage form of  claim 46 , further comprising one or more excipients selected from the group consisting of rate-controlling polymeric materials, diluents, lubricants, disintegrants, plasticizers, anti-tack agents, opacifying agents, pigments, and flavorings. 
     
     
         54 . The solid oral dosage form of  claim 46 , wherein the oral dosage form is a tablet or a capsule. 
     
     
         55 . The solid oral dosage form of  claim 46 , having thereon an enteric coating. 
     
     
         56 . The solid oral dosage form of  claim 55 , wherein the enteric coated solid oral dosage form is a tablet or capsule. 
     
     
         57 . A process for preparing a GnRH agonist,
 wherein the process comprises preparing the GnRH agonist in the presence of a co-solvent system in a manner such that the gelation of the GnRH antagonist is reduced; and   wherein the co-solvent system is used during the final step of the preparation of the GnRH agonist.   
     
     
         58 . The process of  claim 57 , wherein the co-solvent system comprises water and at least one water-miscible solvent. 
     
     
         59 . The process of  claim 58 , wherein the water-miscible solvent is selected from the group consisting of methanol, ethanol, iso-propanol, tent-butanol, acetonitrile and methylene chloride. 
     
     
         60 . A method for preparation of a solid oral dosage form of one or more GnRH agonists, wherein the process comprises mixing the GnRH agonists with one or more anti-gelling agents, wherein at least one anti-gelling agent is a medium chain fatty acid salt and has a carbon chain length of from about 8 to about 14 carbon atoms;
 wherein the final step of the preparation of the GnRH antagonist is conducted in the presence of a co-solvent system in a manner such that the gelation of the GnRH antagonist is reduced.   
     
     
         61 . The process of  claim 60 , wherein the co-solvent system comprises water and at least one water-miscible solvent. 
     
     
         62 . The process of  claim 61 , wherein the water-miscible solvent is selected from the group consisting of methanol, ethanol, iso-propanol, tert-butanol, acetonitrile and methylene chloride. 
     
     
         63 . A method of treating a medical condition treatable by a GnRH agonist comprising administering to a patient suffering from said condition the solid oral dosage form of  claim 46 .