Tier I dissolution was performed using USP paddle apparatus in 900 mL of 0.01 N HCl with 1.0% SLS in each vessel at 37 °C. The paddle rotation speed was 75 rpm.
Samples were obtained at predetermined time points of 10, 20, 30, 45, and 60 min. After 60 min the paddle speed was increased
to 250 rpm for another 15 min before samples at the "infinity" time point were withdrawn. All samples were analyzed using
a UV–Vis spectrometer at a wavelength of 266 nm.
The initial Tier II dissolution method was developed following USP <711>, using a premixed medium containing 900 mL of 0.01 N HCl, 1.0% SLS and 750,000 units/L purified pepsin in each vessel.
The final Tier II dissolution method was modified from USP <711> by using 600 mL of 0.01 N HCl solution containing 750,000 units/L of purified pepsin in each vessel at the beginning
of the test. After 5 min, an additional 300 mL of 0.01N HCl solution containing 3.0% SLS was added to each vessel. This medium
was preheated and kept at 37 °C before transferring. Other method conditions were constant
Capsule switching test procedure.
To identify the cause of dissolution slowdown, a capsule switching test was conducted. The contents of six capsules, which
had been stored at 40 °C and 75% RH for three months and showed dissolution slow down, were fully transferred into six fresh
shells. The fresh capsule shells were from the same batch as those used in the stability study and were stored in a closed
container at ambient conditions. The six emptied (i.e., aged) capsule shells, on the other hand, were refilled with a fresh
drug blend made with the same formula and manufacturing process.
Table I: Dissolution results for capsules stored at 40 °C and 75% relative humidity (RH) for 1 and 3 months.