Amorphous Solid Dispersions Using pH-responsive Cellulose Ethers to Improve Rifapentine Dissolution Properties

The efficacy of rifapentine, an oral antibiotic used in the treatment of tuberculosis, is reduced due to its degradation at gastric pH and low solubility at intestinal pH. We aimed to improve delivery properties in vitro by incorporating rifapentine into pH-responsive amorphous solid dispersions with commercially-available and novel cellulose ethers. Amorphous solid dispersions reduced rifapentine release at gastric pH, with the best performing polymer, achieving >31-fold decrease in gastric area under the curve compared to rifapentine alone. Lower solubility was accompanied by a reduction in the acidic degradation product 3-formylrifamycin compared to rifapentine alone. Certain formulations also showed enhanced apparent solubility and stabilization of supersaturated solutions at intestinal pH, with the best performing formulation showing almost a 4-fold increase.

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Rob Whitehead
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Nammalwar Sriranganathan
Kevin Edgar
Andrew Neilson
Brittany Nichols
Christopher Winslow