Solubilization of butylated hydroxytoluene for oral administration

Collaborative research project with UNC faculty.

Formulation requirements:  mixture of  butylated hydroxytoluene (BHT): 3 mg/kg; Glycerizerin 1 mg/kg;  Ibuprofen sodium salt: 15 mg/kg; and Dextromethaphen hydrobromide: 15 mg/kg for oral administration.

Original approach:

Solution A (1% b-cyclodextrin) : 1.0 g b-cyclodextrin was added 100 ml of Monster and mixed completely (clear solution).

Solution B: 200 mg of BHT was dissolved in 1 ml of 100% ethanol, Sonic 5 min.

3. Solution C: 10 ml of solution B was added to 10 ml of solution A.

4. Solution D: 5 mg Glycerizerin was dissolved in 1ml of water.

5. Solution E (Mix 3): 10 mg of dextromethaphan hydrobromide, 10 mg of iburophen sodium salt and 134 ml of solution D were added to solution C and mix thoroughly.

Problem: Precipitation is observed upon dilution in aqueous mixture and final formulation contains ethanol.

Our solution:

Solubilization of the non-water soluble component using Pluronic F127 through thin film approach in PBS and mixture with the solutions of the other components in PBS.

The final formulation is stable for at least 21 days in room temperature. In vivo experiments are in progress.