Compositions with a Rheological Modifier to Reduce Dissolution Variability

Abstract

The present disclosure provides compositions (e.g., extended release compositions) which exhibit a desirable pharmacokinetic profile of an active agent while providing reduced dissolution sample variability, e.g., in the form of reduced inter-capsule variability and/or a reduction in storage-time dependent change in mean release of the active agent from the composition. Related methods of making and administering the disclosed compositions and formulations are also provided.

1 . A composition comprising:
 a pharmacologically active agent;   about 35% by weight to about 45% by weight, based on total weight of the composition, of a high viscosity liquid carrier material (HVLCM) having a viscosity of at least 5000 cP at 37° C. that does not crystallize neat at 25° C. and 1 atmosphere;   about 31% by weight to about 45% by weight, based on total weight of the composition, of a solvent;   about 2% by weight to about 10% by weight, based on total weight of the composition, of a rheology modifier; and   a cellulose acetate butyrate.   
     
     
         2 . The composition of  claim 1 , wherein the HVLCM is sucrose acetate isobutyrate (SAIB). 
     
     
         3 .- 5 . (canceled) 
     
     
         6 . The composition of  claim 1 , wherein the HVLCM is sucrose acetate isobutyrate (SAIB), the solvent is triacetin, and the rheology modifier is isopropyl myristate (IPM). 
     
     
         7 .- 10 . (canceled) 
     
     
         11 . The composition of  claim 1 , wherein the pharmacologically active agent is selected from opioid, stimulant, and depressant. 
     
     
         12 . The composition of  claim 11 , wherein the pharmacologically active agent is an opioid. 
     
     
         13 . The composition of  claim 11 , wherein the pharmacologically active agent is selected from oxycodone, oxymorphone, hydrocodone, and hydromorphone, either in the free base form or a pharmaceutically acceptable salt form thereof. 
     
     
         14 . The composition of  claim 11 , wherein the pharmacologically active agent is oxycodone. 
     
     
         15 .- 91 . (canceled) 
     
     
         92 . A composition comprising:
 a pharmacologically active agent;   a high viscosity liquid carrier material (HVLCM) having a viscosity of at least 5000 cP at 37° C. that does not crystallize neat at 25° C. and 1 atmosphere;   a solvent;   a rheology modifier; and   a cellulose acetate butyrate,   wherein the composition is encapsulated within a hydroxypropylmethylcellulose capsule, and   wherein the composition within the capsule comprises less than 5% water by weight, based on total weight of the composition within the capsule.   
     
     
         93 . The composition of  claim 92 , wherein the composition comprises less than 2% water by weight, based on total weight of the composition. 
     
     
         94 . The composition of  claim 92 , wherein the HVLCM is sucrose acetate isobutyrate (SAIB). 
     
     
         95 . (canceled) 
     
     
         96 . The composition of  claim 92 , wherein the HVLCM is sucrose acetate isobutyrate (SAIB), the solvent is triacetin, and the rheology modifier is isopropyl myristate (IPM). 
     
     
         97 - 100 . (canceled) 
     
     
         101 . The composition of  claim 92 , wherein the pharmacologically active agent is selected from opioid, stimulant, and depressant. 
     
     
         102 . The composition of  claim 101 , wherein the pharmacologically active agent is an opioid. 
     
     
         103 . The composition of  claim 101 , wherein the pharmacologically active agent is selected from oxycodone, oxymorphone, hydrocodone, and hydromorphone, either in the free base form or a pharmaceutically acceptable salt form thereof. 
     
     
         104 . The composition of  claim 101 , wherein the pharmacologically active agent is oxycodone. 
     
     
         105 .- 295 . (canceled) 
     
     
         296 . A composition comprising:
 an opioid;   sucrose acetate isobutyrate (SAM);   triacetin;   isopropyl myristate (IPM);   cellulose acetate butyrate (CAB);   hydroxyethyl cellulose (HEC); and   silicon dioxide, wherein the silicon dioxide is present in the composition in an amount from about 2.4% by weight to about 5.4% by weight relative to the total weight of the composition.   
     
     
         297 .- 299 . (canceled) 
     
     
         300 . The composition of  claim 296 , wherein the CAB has a number average molecular weight ranging from 66,000 Daltons to 83,000 Daltons. 
     
     
         301 . The composition of  claim 296 , wherein the CAB has at least one feature selected from a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%. 
     
     
         302 .- 304 . (canceled) 
     
     
         305 . The composition of  claim 296 , wherein the silicon dioxide is present in the composition in an amount from about 2.5% by weight to about 2.9% by weight relative to the total weight of the composition. 
     
     
         306 .- 309 . (canceled) 
     
     
         310 . The composition of  claim 296 , wherein the opioid is oxycodone. 
     
     
         311 .- 586 . (canceled)