Is there variability in drug release and physical characteristics of amiodarone chloride from different commercially available tablets? Possible therapeutic implications.
OBJECTIVE
Amiodarone is a low-solubility, high-permeability drug with a narrow therapeutic index and reported bioavailability problems associated with switching formulations. The aim of this study was to identify whether there is variability in drug release and physical characteristics of different commercially available amiodarone hydrochloride formulations in Australia.


METHODS
Four available formulations (innovator Cordarone (COR) and generic products G1, G2 and G3) were tested for drug dissolution, content uniformity, hardness, weight variation, friability and disintegration in accordance with the US Pharmacopeia specifications.


RESULTS
The tested formulations exhibited variable dissolution behaviours: G1 and G3 exhibited the fastest dissolution, G2 dissolution was the slowest and Cordarone showed a medium dissolution. After 3 months' exposure to high temperature (40 +/- 2 degrees C) and relative humidity (75 +/- 5%), the products exhibited a higher degree of disparity, with drug-release profiles of the generics being markedly different from that of Cordarone. This suggests possible implications on bioequivalence for patients who live in warm/tropical regional areas. Most products met the US Pharmacopeia specifications for drug-content uniformity and other test physical characteristics.


CONCLUSIONS
The results suggested that variability in drug release profiles in vitro of amiodarone formulations might be a potential indicator of compromised bioavailability, causing possible interference with the therapeutic response of the drug.
Ngo
Suong N T
SN
The University of Adelaide, School of Animal and Veterinary Sciences, Roseworthy, Australia. suong.ngo@adelaide.edu.au
Barnes
Timothy
T
D000638:Amiodarone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001315:Australia; D001682:Biological Availability; D004355:Drug Stability; D004356:Drug Storage; D016568:Drugs, Generic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006244:Hardness; D006813:Humidity; D010602:Pharmacopoeias as Topic; D012995:Solubility; D013607:Tablets; D013696:Temperature; D014481:United States
D000889:Anti-Arrhythmia Agents; D016568:Drugs, Generic; D013607:Tablets; D000638:Amiodarone