Journal
JOURNAL OF PHYSICAL CHEMISTRY B
Volume 120, Issue 34, Pages 9161-9165Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jpcb.6b05417
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Funding
- NSF [DMR-1310266]
- Harvard MRSEC [DMR-1420570]
- National Science Foundation under NSF [ECS-0335765]
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The bioavailability of hydrophobic drugs strongly increases if they are formulated as amorphous materials because the solubility of the amorphous phase is much higher than that of the crystal. Moreover, the stability of these particles against crystallization during storage increases with decreasing particle size. Hence, it is advantageous to formulate poorly water soluble drugs as amorphous nano particles. The formulation of an amorphous structure is often difficult because many of these drugs have a high propensity to crystallize. This difficulty can be overcome if drugs are spray dried using a microfluidic nebulator we recently developed. However, these nanoparticles agglomerate when they come in contact with each other, and this compromises the stability of their amorphous structure through crystallization. To improve their stability, we coat the nanoparticles with a sterically stabilizing polymer layer; this can be accomplished by co-spraying them with an excipient. However, this excipient must meet strict solubility limits, which severely limit the choice of polymers. Alternatively, the nanoparticles can be sterically stabilized by spraying them directly into a polymeric matrix; this enables a much wider choice of stabiliziting polymers.
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