469561 Tunable Drug Loaded Stable and Fast Release Amorphous Composites Production Using Mesoporous Neusilin®UFL2

Friday, November 18, 2016: 2:10 PM
Continental 4 (Hilton San Francisco Union Square)
Mohammad Azad1,2, Jacqueline Moreno3, Meng Li4 and Rajesh Dave3, (1)Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, (2)Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, MA, (3)New Jersey Institute of Technology, Newark, NJ, (4)Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ

Literature has revealed that there may exist possibility of greatly reduced mobility of drug molecules due to confinement, which could occur through several different manners. Impregnation of poorly water drug solutions in to mesoporous materials is one such attractive approach for nano-confinement that leads not only to creation of amorphous state but also its stability due to what may be the poor molecular mobility. Such as approach is examined here to increase the aqueous solubility and thus the bioavailability of poorly soluble drugs since it allows formation of drug amorphous state which generally exhibit higher apparent solubilities than their crystalline counterparts. Unfortunately, mesoporous materials such as silica are expensive and proprietary, and not easily available in bulk quantities. In this work, Neusilin® UFL2 as commercially available mesoporous amorphous materials was used to prepare amorphous drug composites of the model poorly soluble drugs Fenofibrate and Itraconazole via impregnation. Drug loading could be tuned as low as 1.0% (w/w) to as high as 30%. PXRD, DSC, and Raman spectroscopy were used to assess the amorphousness/crystallinity of the drug in the impregnated composites after formation as well as after storage. It was shown that the impregnated drug composites are stable for three months even stored at 40°C and 75% relative humidity. Re-crystallization of the amorphous drug was completely suppressed in the composites due to the confinement effect provided by the mesopores of Neusilin® UFL2. The amorphous drug composites result in higher apparent solubility and faster release/dissolution rate of the model drugs compared to crystalline counterparts. UV imaging technique, a real-time and sample sparing method, was used to qualitatively differentiate the amorphous and crystalline drug dissolution besides the conventional USP II dissolution. In conclusion, preparation of amorphous drug composites using Neusilin® UFL2 appears to be promising as a stable amorphous drug delivery vehicle providing a rapid drug release and subsequently bioavailability enhancement.

Keywords: Mesoporous Neusilin®, Impregnation, Amorphous Drug Composites, Stability, Dissolution Enhancement

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