The effect of using different HPMC hard capsule shells on the in vitro dissolution profile of acetaminophen powder wasinvestigated. Use of HPMC capsule shells from different manufacturers resulted in different in vitro dissolution profiles.These differences were unrelated to the presence or absence of a gelling agent (carrageenan) in the capsule shells whenpotassium was absent from the dissolution media. Even though these differences can be significant from a regulatorypoint of view, they do not translate into differences in the in vivo performance. This is because, in some cases, thesimilarity criterion of f2 ≥ 50 is too strict.
Using HPMC capsules from different manufacturers could, at least from a regulatory point of view, result insignificant differences in the dissolution performance for highly soluble drugs like acetaminophen, where drug dissolution could be so fast that the capsule shell rupture and dissolution rates would be reflected in the overall drug release profile. However, these differences might not always be reflected by significant differences in the in vivo performance. This is because drug dissolution is not always the rate-determining step of drug absorption. In such cases, a dissolution profile similarity criterion of f2 ≥50 could often be too strict, particularly in the absence of strong segment-dependence of the API’s permeability.Therefore, it would be reasonable to look further into relaxing the current dissolution profile similarity criterion in such cases and/or investigate the use of some alternative dissolution comparison methods (with betterability to forecast the differences in the in vivo product performance) following further study of the interplaybetween dissolution, gastric emptying and absorption rates.
Jozef Al-Gousous1, Michael B. Bolger2, Fernando Diez3, Justin Kalafat3, Peter Langguth1*
1Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
2Simulations Plus Inc, Lancaster, CA, USA
3ACG World, Mumbai, India