461681 Application of PAT-Based Feedback Control for the Crystallization of Pharmaceuticals in Porous Media

Friday, November 18, 2016: 8:30 AM
Continental 5 (Hilton San Francisco Union Square)
David Acevedo1, Jing Ling2, Keith Chadwick2 and Zoltan K. Nagy1, (1)School of Chemical Engineering, Purdue University, West Lafayette, IN, (2)Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN

The development of new drug delivery methods to tailor the desired drug release have been of major interest such as substrates, polymer films and microspheres. The drug release can be affected by various attributes of the polymer properties such as molecular weight, size and size distribution, porosity, morphology and make-up. However, the purpose of this work is to evaluate the benefits of controlling the bulk crystallization in the presence of alginate porous particles. The main objective is to increase the drug loading (DL) in the alginate beads and minimizing the heterogeneous nucleation occurring in the bulk system. Two types of controlled cooling profiles and the model-free Direct Nucleation Control (DNC) strategy were evaluated. A mean DL from 49 to 69 % was achieved through the various scenarios. The application of DNC increased or maintained the mean DL achieved compared to the cooling only scenarios, while a decrease of about 75 % was observed in the batch-to-batch variability. SEM images showed that crystals of different crystal size distribution (CSD) were obtained for the various cooling scenarios, which can be related to the different operating trajectories in the phase diagram achieved during the feedback control approaches. The possibility of manipulating the CSD of particles within the polymer beads can be used to tailor dissolution profile and bioavailability. The work demonstrates the benefits of using feedback control approaches to increase DL, decrease batch-to-batch variability and control dissolution behavior of drug-loaded polymer microspheres.

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