Evaluation of In-Use Stability of Anticoagulant Drug Products: Warfarin Sodium.
The objective of the study was to evaluate the stability of warfarin products during use by patients or caregivers. For evaluation, three commercial products manufactured by different processes were selected and placed at 30°C/75%RH to simulate in use condition. Samples were withdrawn up to 12 weeks and analyzed for the physicochemical changes. Scanning electron microscopy demonstrated increasing holes and craters in the tablets over the timeframe. Near-infrared chemical imaging and powder X-ray powder diffraction corroborated the change arising from conversion of crystalline to amorphous forms of the drug. Hardness and disintegration time of the tablets were found to increase progressively. With increasing time, moisture contents of the products were found to increase and consequent decrease in isopropyl alcohol content of the product. Dissolution of the tablets in media at pH 4.5 demonstrated discrimination between crystalline and amorphous drug products. Overall, percent drug dissolved in each product at 30 min was found to decrease with increasing exposure time. Dissolution of drug decreased from 54% to 38% and 82% to 54% for the two products while the third product maintained consistently high level of dissolution. These results suggest that the drug product quality attributes can change during use.
Division of Product Quality Research, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, Maryland 20993-002.
Agnes
A
Nguyenpho
Division of Product Quality Research, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, Maryland 20993-002.
Anthony B
AB
Ciavarella
Division of Product Quality Research, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, Maryland 20993-002.
Akhtar
A
Siddiqui
Division of Product Quality Research, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, Maryland 20993-002.
Ziyaur
Z
Rahman
Division of Product Quality Research, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, Maryland 20993-002.
Sohail
S
Akhtar
Division of Product Quality Research, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, Maryland 20993-002.
Robert
R
Hunt
Division of Product Quality Research, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, Maryland 20993-002.
Maxwell
M
Korang-Yeboah
Division of Product Quality Research, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, Maryland 20993-002. Electronic address: mkhan@pharmacy.tamhsc.edu.
Mansoor A
MA
Khan
D000925:Anticoagulants / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D004355:Drug Stability; D006244:Hardness; D006813:Humidity; D011208:Powders / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000737:chemistry; D013696:Temperature; D014859:Warfarin / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
D000925:Anticoagulants; D011208:Powders; D013607:Tablets; D014859:Warfarin
X-ray powder diffractometry; amorphous; clathrates; crystallinity; dissolution; near-infrared spectroscopy; stability