Active Agent Formulations, Methods of Making, and Methods of Use
An active agent composition includes particles containing a water-insoluble active agent or an active agent with a significant food effect; and a ternary amine polymer having both hydrophobic (meth)acrylate units and acid-soluble (meth)acrylate units, and an acidifying agent; wherein upon ingestion by a human subject, the acidifying agent facilitates the dissolution of the ternary amine polymer in the gastrointestinal tract.
1 . A method of producing a solid dosage form, comprising:
producing particles comprising a water-insoluble active agent or an active agent with a significant food effect, and a ternary amine polymer; and
combining the particles with the acidifying agent to produce the dosage form, wherein upon ingestion of the dosage form by a human subject, the acidifying agent facilitates the dissolution of the ternary amine polymer in the gastrointestinal tract.
2 . The method of claim 1 , wherein the particles have a diameter of 200 nanometers to 200 micrometers.
3 . The method of claim 1 , wherein the ternary amine polymer has both hydrophobic (meth)acrylate units and acid-soluble (meth)acrylate units.
4 . The method of claim 3 , wherein the ternary amine polymer comprises a butyl methacrylate-(2-dimethylaminoethyl)methacrylate-methyl methacrylate copolymer.
5 . The method of claim 1 , further comprising disposing the particles and the acidifying agent on an inert core.
6 . The method of claim 5 , wherein the inert core has an average diameter of 5 to 500 μm.
7 . The method of claim 1 , further comprising combining the particles with am ionic strength modifying agent in addition to the acidifying agent.
8 . The method of claim 1 , wherein the acidifying agent is an organic acid.
9 . The method of claim 8 , wherein the organic acid is citric acid, maleic acid, fumaric acid, succinic acid, or a combination thereof.
10 . The method of claim 8 , wherein the organic acid is fumaric acid and succinic acid.
11 . The active agent composition of claim 10 , wherein the ratio of the organic acid to the ternary amine polymer is about 0.3 to about 2.
12 . The method of claim 1 , wherein producing particles comprises forming an aqueous solution of the ternary amine polymer, forming a suspension of the active agent in the solution, and mixing or milling the suspension to produce suspended particles.
13 . The method of claim 12 , further comprising spraying the suspended particles over a powder bed comprising a plurality of inert cores to disperse the suspended particles on the inert cores.
14 . The method of claim 12 , wherein the suspended particles have an average particle size of 200 to 700 nm.