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Calcium Coordination Solids for pH-Triggered Release of Olsalazine.

  • Author(s): Levine, Dana J;
  • Gonzalez, Miguel I;
  • Legendre, Christina M;
  • Runčevski, Tomče;
  • Oktawiec, Julia;
  • Colwell, Kristen A;
  • Long, Jeffrey R
  • et al.
Abstract

Calcium coordination solids were synthesized and evaluated for delivery of olsalazine (H4 olz), an anti-inflammatory compound used for treatment of ulcerative colitis. The materials include one-dimensional Ca(H2 olz)⋅4 H2 O chains, two-dimensional Ca(H2 olz)⋅2 H2 O sheets, and a three-dimensional metal-organic framework Ca(H2 olz)⋅2DMF (DMF=N,N-dimethylformamide). The framework undergoes structural changes in response to solvent, forming a dense Ca(H2 olz) phase when exposed to aqueous HCl. The compounds Ca(H2 olz)⋅x H2 O (x=0, 2, 4) were each pressed into pellets and exposed to simulated gastrointestinal fluids to mimic the passage of a pill from the acidic stomach to the pH-neutral intestines. All three calcium materials exhibited a delayed release of olsalazine relative to Na2 (H2 olz), the commercial formulation, illustrating how formulation of a drug within an extended coordination solid can serve to tune its solubility and performance.

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