Improving Stability and Dissolution of Amorphous Clofazimine by Polymer Nano-Coating
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To inhibit the surface crystallization and enhance the dissolution of the basic amorphous drug clofazimine by polymer nano-coating.
The free surface of amorphous clofazimine was coated by dip coating in an alginate solution at pH 7. The stability of the coated amorphous drug against crystallization was evaluated by X-ray diffraction and light microscopy. The effect of coating on dissolution rate was measured in simulated gastric fluid in an USP-II apparatus at 37°C.
At pH 7, the weak base clofazimine (pKa = 8.5) is positively charged, while the weak alginic acid (pKa = 3.5) is negatively charged, allowing coating by electrostatic deposition. Coated amorphous particles remain nearly amorphous after one year under the accelerated testing condition 40°C/75% R.H. and show faster dissolution than uncoated particles. In the first hour of dissolution, coated amorphous particles dissolve 50% faster than uncoated amorphous particles, and a factor of 3 faster than crystalline particles of the same size.
A pharmaceutically acceptable polymer, alginate, is coated on amorphous clofazimine by electrostatic deposition and effectively inhibits its surface crystallization and enhances its dissolution rate. This is the first time the nano-coating technique is applied to a basic drug using the principle of electrostatic deposition, demonstrating the generality of the approach.
Key WordsAmorphous pharmaceutical clofazimine crystallization dissolution polymer coating stability wetting
Differential scanning calorimetry
Sodium dodecyl sulfate
Simulated gastric fluid
Acknowledgments and Disclosures
We thank the Bill and Melinda Gates Foundation for financial support, Yuhui Li for assistance with dissolution measurements, and Mark Sacchetti, Niya Bowers, Phil Goliber, and Ellen Harrington for helpful discussions.