White Paper

Comparative Human in-vivo Study And The Impact Of The Dissolution Rate On Bioequivalence

Source: Capsugel® | Lonza Pharma & Biotech

By Sven Stegemann, Sudershan Vishwanath, Ravi Kumar, Dominique Cade, Missy Lowery, Keith Hutchison, Michael Morgen, Aaron Goodwin and Chang Lee

Capsules

Rapid and consistent in-vivo drug dissolution is critical for drug absorption. In-vitro dissolutions tests are used to predict in-vivo disintegration and dissolution properties of drug products. The in-vitro disintegration and dissolution times of tablets and capsules can vary significantly based on their composition and processing. Though small differences in-vitro dissolution are not expected to result in significant in-vivo performance differences, the slight in-vitro dissolution delay observed by over-encapsulation for double blind clinical trials, as well as switching from gelatin to HPMC capsules often raises concerns on the potential impact on in-vivo bioavailability. While it is accepted that the in-vitro dissolution delay of about 5 minutes caused by over-encapsulation with gelatin capsules of immediate release (IR) tablets or powder formulation does not lead to non-bioequivalence, no data on bioequivalence exist for over-encapsulation with an HPMC capsule having a dissolution lag time of around 10 minutes. To assess the potential impact, a comparative investigation was performed using in-vitro dissolution, PK simulation and human bioequivalence comparing an IR fixed dose combination compressed caplet containing three different rapidly-absorbed drugs over-encapsulated with gelatin capsules and the same caplet over-encapsulated with HPMC capsules made by a thermo-gelation process.

CapsugelĀ® | Lonza Pharma & Biotech