Abstract
Purpose :
PRINT (Particle Replication in Non-wetting Templates) is a versatile manufacturing technology used to produce precisely sized and shaped drug particles from the nanometer to millimeter size range with high batch to batch reproducibility and dose uniformity. PRINT is compatible with a wide variety of drugs and excipients, including many classes of small molecules as well as biologics, and can be used in combination products with multiple Active Pharmaceutical Ingredients (APIs). The AR-1105 manufacturing process used to make sustained release, dexamethasone implants requires multiple steps to incorporate dexamethasone into a polymer matrix. Heat and mechanical agitation are used to generate the intermediate blend from a solid-solid mixture. By tracing the Dexamethasone content throughout the manufacturing process (twin-screw extrusion, ball milling, and lamination) we can assess the API incorporation efficiency for each step of the process. Demonstrating control of API content throughout the manufacturing process is critical to the performance of the sustained release implant.
Methods :
The incorporation efficiency of dexamethasone at the intermediate manufacturing steps was analyzed using optical imaging and dexamethasone content by HPLC. The reproducibility of the dexamethasone content in the extrudate, the milled powder, and the intravitreal implant was analyzed for multiple lots.
Results :
Incorporation efficiency was determined by comparing the charged dexamethasone to the measured dexamethasone content by HPLC for each processing step. Average incorporation efficiency across two formulations for the extrudate, milled blend, and implants was >97%, >95%, and >92%, respectively. Approximately 98% of dexamethasone was retained between process step transitions. The cross-sectional images show the uniform incorporation of dexamethasone within the polymer matrix.
Conclusions :
PRINT technology can be used to fabricate particles and implants using a variety of APIs and excipients. Here we demonstrate control over the manufacturing process for dexamethasone intravitreal implants. The greatest loss of dexamethasone occurs after the initial mixing and extrusion of the material. Incorporation of dexamethasone in the polymer matrix was demonstrated throughout the manufacturing process and across multiple batches of two different formulations.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.