Performance qualification of a new hypromellose capsule: Part II. Disintegration and dissolution comparison between two types of hypromellose capsules.

This Part II paper describes the disintegration and dissolution aspects of the qualification of a new hypromellose capsule (HPMC Shell 2). This new capsule does not contain any gelling agent, and is manufactured by a thermal gelation process. Rupture time of the carrageenan-containing capsule (HPMC Shell 1) and HPMC Shell 2, as measured by an improved real-time detection method, showed only slight differences that did not manifest in vivo. The absence of a gelling agent appeared to give HPMC Shell 2 advantages in dissolution in acidic media and in buffers containing potassium ions. Slow drug release of HPMC Shell 1 in 0.1M HCl was attributed to the interaction of carrageenan with drug compounds; whereas the presence of potassium ions, a gelling promoter for carrageenan, caused delay in capsule opening and larger capsule-to-capsule variation. Disintegration and dissolution performances of both hypromellose capsules are comparable in other dissolution media tested. Based on the superior dissolution performances and quality attributes in terms of physical, mechanical and processability that were detailed in Paper I, the new hypromellose capsule was satisfactorily qualified and has since been used in nearly 20 investigational new drug (IND) compounds.