Find out how our team successfully developed and validated a dissolution method to support quality control for continuously manufactured clinical trial materials.
Metrics’ scientists were faced with the challenge of troubleshooting poorly soluble HPMC capsule formulation containing a BCS Class II/IV compound with a tartaric acid excipient (Compound E) intended for an immediate-release capsule.
Previous methodology employed a single pull point (30 minute) with 0.1N HCl as the dissolution medium. Prior to regulatory submission, a robust and discriminating dissolution method for Compound E was necessary.
The compound had calculated pKa values of 0.2 and 4.1, and limited solubility in aqueous solutions above pH 5.0. Improved solubility and bioavailability of were shown in the presence of an acidulant, which acted as a functional excipient by lowering the pH environment in the capsule.
Metrics’ scientists had two objectives. First, to discriminate between drug product formations that had three different levels of acidulant by evaluating low, target, and high acidulant levels.
Second, to generate a release profile capable of supporting a two-point specification of Q = 25 at 30 min and Q = 80 at 60 min to ensure continued quality control.
Download the whitepaper to explore how our team solved another complex OSD puzzle, enabling a phase III study to progress .