Improving cyclodextrin complexation of a new antihepatitis drug with glacial acetic acid.

Abstract

The purpose of this study was to develop and evaluate a solid nonaqueous oral dosage form for a new hepatitis C drug, PG301029, which is insoluble and unstable in water. Hydroxypropyl-beta-cyclodextrin (HPbetaCD) and PG301029 were dissolved in glacial acetic acid. The acetic acid was removed by rotoevaporation such that the drug exists primarily in the complexed form. The stability of formulated PG301029 was determined upon dry storage and after reconstitution in simulated intestinal fluid (SIF), simulated gastric fluid (SGF), and water. Formulated PG301029 was found to be stable upon storage and can be reconstituted with water to a concentration 200 times that of the intrinsic solubility. Once reconstituted, the powder dissolves rapidly and PG301029 remains stable for 21 hours in SGF, SIF, and water. The unique use of acetic acid and HPbetaCD results in a solid dosage form of PG301029 that is both soluble and stable in water.

• Authors: Jennifer L H Johnson, Yan He, Akash Jain, Samuel H Yalkowsky
• Journal: AAPS PharmSciTech (AAPS PharmSciTech) Vol. 7 Issue 1 Pg. E18 (Feb 24 2006) ISSN: 1530-9932 [Electronic] United States
• PMID: 16584148 (Publication Type: Journal Article)

Chemical References

• 5-phenyl-3-thioureido-1,2,4-thiadiazole
• Antiviral Agents
• Thiadiazoles
• beta-Cyclodextrins
• 2-Hydroxypropyl-beta-cyclodextrin
• Acetic Acid

Topics

• 2-Hydroxypropyl-beta-cyclodextrin
• Acetic Acid (administration & dosage)
• Antiviral Agents (administration & dosage, analysis, chemistry)
• Calorimetry, Differential Scanning
• Chromatography, High Pressure Liquid
• Drug Stability
• Hepatitis C (drug therapy)
• Solubility
• Thiadiazoles (administration & dosage, chemistry)
• beta-Cyclodextrins (administration & dosage)