Dissolution composition for examining drug solubility

Abstract

There are described solid compositions or examining drug solubility comprising bile salts and phospholipids, optionally containing buffer components suitable for preparation of intestinal media that simulate the composition of the intestinal fluids in fasted and fed states.

1 - 21 . (canceled) 
     
     
         22 . A composition for forming a simulated gastrointestinal medium to determine solubility or dissolution of a pharmacological compound, comprising:
 a homogeneous solid dissolution composition in a granular or powder form
 comprising at least one bile salt and at least one phospholipid configured to be added to an aqueous medium comprising at least one buffer component and at least one osmotic agent to form a simulated gastrointestinal medium, the simulated gastrointestinal medium configured to receive at least one of a pharmacological compound, a physiological compound and a dosage form to determine a solubility or dissolution characteristic of the pharmacological compound, physiological compound or dosage form. 
   
     
     
         23 . The composition of  claim 22 , wherein the dissolution composition is added to the aqueous medium in an amount such that the at least one bile salt and at least one phospholipid have a mole ratio between about 1:1 and 20:1. 
     
     
         24 . The composition of  claim 22 , wherein the dissolution composition is added to the aqueous medium in an amount such that the simulated gastrointestinal medium has a 0.1% w/v to 5% w/v of the at least one bile salt and the at least one phospholipid, micelles or mixed micelles with mean particle diameters below 100 nm, a pH between about pH 1 and pH 10 and an osmolality less than about 800 mOsmol/kg. 
     
     
         25 . The composition of  claim 22 , wherein the dissolution composition is added to the aqueous medium in an amount such that the simulated gastrointestinal medium simulates a fasted state intestinal fluid with a pH between about 6.0 and 7.0 and a combined weight per volume of about 0.1% to 1% of the at least one bile salt and the at least one phospholipid. 
     
     
         26 . The composition of  claim 25 , wherein the dissolution composition is added to the aqueous medium in an amount such that the simulated gastrointestinal medium has an osmolality of between about 250 and 290 mOsmol/kg. 
     
     
         27 . The composition of  claim 22 , wherein the dissolution composition is added to the aqueous medium in an amount such that the simulated gastrointestinal medium simulate a fed state intestinal fluid with a pH to about 4.5 to 5.5 and a combined weight per volume of about 0.2% to 2.5% of the at least one bile salt and the at least one phospholipid. 
     
     
         28 . The composition of  claim 27 , wherein the dissolution composition is added to the aqueous medium in an amount such that the simulated gastrointestinal medium has an osmolality of about 650 to 690 mOsmol/kg. 
     
     
         29 . The composition of  claim 22 , wherein the solid dissolution composition has a water content of less than about 5% by weight. 
     
     
         30 . The composition of  claim 22 , wherein the at least one phospholipid is selected from the group of phospholipids consisting of lecithin, enzyme hydrolyzed lecithin, diacyl phospholipids, monoacyl phospholipids, and a mixture of diacyl phospholipids and monoacyl phospholipids comprising about 10% to 90% by weight monoacyl phospholipids. 
     
     
         31 . The composition of  claim 22 , wherein the solid dissolution composition is a free flowing powder. 
     
     
         32 . The composition of  claim 22 , wherein the bile salt and the at least one phospholipid have a mole ratio of between about 1:1 and 10:1. 
     
     
         33 . The composition of  claim 22 , wherein the bile salt and the phospholipid have a mole ratio of about 4:1. 
     
     
         34 . The composition of  claim 22 , wherein the bile salt is selected from the group consisting of sodium cholate, sodium taurocholate, sodium glycocholate, sodium deoxycholate, sodium taurodeoxycholate, sodium glycodeoxycholate, sodium ursodeoxycholate, sodium chenodeoxycholate, sodium taurochenodeoxycholate, sodium glyco chenodeoxycholate, sodium cholylsarcosinate, and sodium N-methyl taurocholate. 
     
     
         35 . The composition of  claim 22 , further comprising at least one fatty acid and wherein a mole ratio of the at least one phospholipid and the at least one fatty acid is between about 10:1 and 1:10. 
     
     
         36 . The composition of  claim 35 , wherein the monoacyl phospholipid and the at least one fatty acid have a mole ratio of about 1:1. 
     
     
         37 . The composition of  claim 35 , wherein the at least one fatty acid is selected from the group consisting of lauric acid, myristic acid, palmitic acid, oleic acid and arachidonic acid. 
     
     
         38 . The composition of  claim 22 , wherein the simulated gastrointestinal medium further comprises one additional component selected from a fatty acid, a cholesterol, a monoglyceride, a diglyceride, a triglyceride, a carbohydrate, a protein and an enzyme. 
     
     
         39 . The composition of  claim 22 , wherein the solid dissolution composition further comprises at least one additional component selected from the group consisting of a fatty acid, a cholesterol, a monoglyceride, a diglyceride and a triglyceride.