Analytical Support for Accelerated Product Development and Effective QC Testing

Situation: Our client needed assay, related substance and dissolution method development to support the reformulation of two different extended release tablet formulations each containing three different actives (total of four different actives); the active with the highest potency was present at levels over hundred times higher than the level of the lowest strength active. Validatable methods for each product (supported by specificity, sensitivity, forced degradation, recovery studies) had to be in place to test prototype samples within three to four weeks.

Task: Develop effective QC methodologies to simultaneously monitor potency and related substances, reduce sample preparation labor and solvent cost associated with previously employed procedures; develop meaningful and differentiating dissolution parameters for each active despite the different solubility, stability and targeted release profile characteristics for each active. Reduce the number of the dissolution set ups involved in current client methodologies (three different set ups).

Action: AAIPharma developed a gradient separation that monitored in one run two of the actives for each formulation and all eight relevant related substances associated with the three actives; a simple dilution was necessary to monitor the potency of the third active. System/sample calibration for all actives of each product was carried with a single standard solution. AAIPharma also developed discriminating dissolution conditions utilizing a single dissolution system (apparatus and medium). Dissolution solutions were measured with a single HPLC separation, single injection without requiring a sample dilution for any of the actives.

Result: The client was able to meet the aggressive timeline requirements for formulation selection. Because of the QC friendly character of the methods, testing of prototypes consumed less resource than originally anticipated. Discriminating dissolution conditions increased the possibility of achieving the desired release characteristics for each active, thus keeping the bioequivalence costs as low as possible.