Abstract

The objective of this study was to identify if the root cause of dissolution was from the HPMC shell differences and/or the insufficient robustness of dissolution method. Studying the dissolution behavior of 40 and 150 mg granules (with and without shells), followed by capsule dissolution with switched shells, the sink condition can be verified by the extent of granule dissolutions with switch shells. The effect of the apparatus, agitation speed and medium deaeration on dissolution variations was also studied. The surface dissolution behavior for shells with different moisture levels was probed in an aqueous medium utilizing an ActiPix SDI300 surface dissolution imaging system. The inter-vessel variability of 150 mg granules was low, while for 40 mg granules, the inter-vessel variability of the 40 mg granules was slightly higher. Basket method exhibited much slower dissolution and higher percent relative standard deviation (RSD) at early sampling-points when comparing the paddle apparatus. Degassed medium reduced the capsule-to-capsule variations at early sampling-points and improved the dissolution rate. The 40 mg granule with the 150 mg capsule shell had an average dissolution release of 88% at 20 min with 7.4% RSD for n = 6 samples. It was slower and more variable as compared to 96% release with 2.8% RSD from the original 40 mg capsules (40 mg granule in 40 mg capsule shell). Capsules with un-dried shells exhibited a slower and variable dissolution at early sampling-points, whereas a faster and consistent dissolution was obtained for capsules with dried shells. The root cause of the undesirable dissolution variations at early sampling-points and the intermittent failure for stage 1 specification was the higher moisture content in the HPMC shells of the high strength capsules. Insufficient hydrodynamics in dissolution vessels contributed to the intermittent low drug release, higher agitation speed and medium deaeration can improve dissolution rate and reduce dissolution variations for HPMC shells.

Key words: Hypromellose capsule, dissolution, hydrodynamics, medium deaeration.