Performance qualification of a new hypromellose capsule: Part I. Comparative evaluation of physical, mechanical and processability quality attributes of Vcaps Plus ®, Quali-V ® and gelatin capsules

Abstract

This Part I paper describes the qualification of a new high performance hypromellose (hydroxypropyl methylcellulose, HPMC) capsule shell which contains no gelling agent and is dissolution friendly. The development history and the test results for a series of quality attributes including scanning electron microscopy, hygroscopicity, machineability, weight variation, powder leakage, mechanical strength, stability, cross-linking, animal and human pharmacokinetic results are reported. Comparisons to gelatin and HPMC capsule containing carrageenan showed the new HPMC capsule is superior in terms of mechanical strength, hygroscopicity and compatibility with a wide range of drugs. Specifically, the new HPMC capsule demonstrated improved weight variation, machineability and powder leakage than the HPMC capsule containing carrageenan. And the new capsule demonstrated a broader applicability than gelatin capsule for new drug development due to its inertness and compatibility for a wide range of excipients including those used for liquid fill formulations. In the second phase of qualification, disintegration and dissolution properties of the new HPMC were evaluated and reported in a Part II paper for 10 new clinical compounds with a variety of formulations optimized based on the biopharmaceutical classification system of solubility and permeability. Based on the superior performance, the new HPMC capsule is satisfactorily qualified and has since been used successfully for nearly 20 investigational new drug (IND) compounds.