Effect of accelerated storage conditions on the dissolution and bioavailability of amitriptyline from sustained release capsules

ABSTRACT

Amitriptyline commercially available as sustained release capsules was stored at different conditions of temperature and relative humidity [RH] namely ambient room temperature and humidity 40°C/30 RH and 40°C/80% RH. The dissolution rate profiles before and after storage were compared. The bioavailability of amitriptyline in beagle dogs before storage was compared to that after storage at ambient conditions and stressed conditions [40°C/80% RH]. A remarkable change in the physical appearance was observed when the capsules were stored for16 weeks at 40°C/80% RH as the beads inside the hard gelatin capsules were agglomerated. A small ddecrease in dissolution rate was observed for capsules stored at 40°C/30% RH [up to 16 weeks] and at ambient conditions [up to 50 weeks]. An initial decrease in the percentage dissolved after 2 weeks of storage at 40°C/80% RH was noticed, followed, followed by a considerable increase upon storage for 16 weeks. The rate and extent of absorption from capsules stored at ambient conditions for 50 weeks were equivalent to those from pre-storage capsules. However a significant decrease in the rate and extent of absorption was observed for capsules stored for 16 weeks at 40°C/80% RH. Degradation and/or complexation of amitriptyline with the excipients in the formulation might explain the poor bioavailability for capsules exposed to stressed conditions