Purpose: To evaluate buprenorphine diffusion through oral tissue culture comparing dosage forms prepared by microdeposition versus a marketed sublingual tablet and a marketed buccal film.
Methods: MatTek ORL-200 24-well plate containing oral cell tissue cultures was utilized as the diffusion membrane. The tissues were equilibrated in a 5% CO2 chamber set to 37ºC and 95% relative humidity. 300uL of Dulbecco's Phosphate Buffered Saline (DPBS) receiver media was added to each well within the 24-well plate and placed into the CO2 chamber overnight. The following morning the tissue inserts were removed from the assay medium and transepitheleal electrical resistance (TEER) was measured on each tissue inset to assure viability following the overnight equilibrium. The tissues were then placed into a 24-well plate containing 300uL of pre-equilibrated receiver media. Each inset was prewetted with 25uL of DPBS prior to applying the respective samples to the donor side of the tissue inserts followed by an additional 25uL of DPBS onto the top of each sample. The 24-well plate containing each tissue insert was returned to the incubator following the elapsed time. The tissue inserts were transferred to a fresh 24-well plate containing 300uL of DPBS and returned to the incubator for the additional specified time. 300uL of receiver media from each well of the 24-well plate was transferred to an HPLC vial and analyzed via Ultra High Performance Liquid Chromatography (UPLC). The experimental sequence was repeated for all time points. The cumulative buprenorphine concentrations were plotted with respect to time.
Results: The microdeposited buprenorphine outperformed the buprenorphine sublingual tablet and the buprenorphine buccal film.
Conclusion: For improved delivery of buprenorphine, microdeposition technology represents a viable alternative to the traditional sublingual tablet or buccal film.
Scott Barnhart– ARx Technical Director, ARX LLC, Glen Rock, Pennsylvania
Ivanny Jacome– ARx R&D Technician, ARX LLC, Glen Rock, Pennsylvania
Adam Usciak– ARx Analytical Chemist, ARX LLC, Glen Rock, Pennsylvania