Comparative evaluation of mixing dynamics in USP apparatus 2 using standard USP vessels and PEAK™ vessels

Abstract

Objective: To compare dissolution results for commercial for-mutations in USP Apparatus 2 using conventional USP vessels and PEAK™ vessels. Methods: Dissolution studies using commercially available disintegrating tablets of acetaminophen and naproxen sodium were conducted in USP Apparatus 2 using USP and PEAK™ vessels. The effect of four different RPMs (25, 50, 75 and 100) and three dissolution media (water, 1% Tween SO and phosphate buffer, pH 5.8 and 7.4 for acetaminophen and naproxen sodium, respectively) on the mixing dynamics in the two vessels were investigated. Both nondeaerated and deaerated media -were employed in the dissolution studies. To confirm the differences in mixing, if any, is only due to the formation of a cone at the bottom of the USP vessel, dissolution studies on these tablets were also performed in USP Apparatus I. Results: Significant differences (p <0.05) -were detected for up to 20 minutes in the release of naproxen sodium tablets at RPM 50, 75 and 100 in nondeaerated and deaerated phosphate buffer (pH 7.4). However, no significant difference in mixing was seen at 25 RPM. Release of the drug from naproxen sodium tablets showed significant differences (p<0.05) in both nondeaerated and deaerated water and 1% Tween 80 with PEAK™ vessels showing greater release. Interestingly, no significant difference was detected in the release profile using USP Apparatus I indicating that the different mixing profile is in fact due to deposition of powder at the bottom of the USP vessel. Acetaminophen tablets showed differences in mixing in the two vessels only at RPM 25. There was no difference in the mixing of acetaminophen in the USP Apparatus 1 at 25 RPM. No difference was detected in water and I % Tween SO at 25 RPM or at higher RPMs of 50, 75 and 100 in phosphate buffer (pH 5.8). Conclusions: PEAK™ vessels show improved mixing when compared to USP vessels indicated by an increase in the release profile (and a decrease in variability) with the PEAK™ vessels. This is due to the shape of the vessel which helps to displace any cone effect at the bottom of the vessel. It is possible that tablets that may fail to meet USP dissolution criteria do so because of poor particle dispersion which can be overcome by the use of PEAK™ vessels.