Dose Formulation Analysis is an essential step in regulated nonclinical studies to assure that correct doses have been administered to underpin toxicokinetic assessments. Based on years of experience, KCAS has built a stand-alone team dedicated to dose form analysis. We recognize that robust analytical methods, rapid turnaround, and efficient communication are vital to ensure quality dose formulation data for your GLP studies and your projects’ success.
The preparation of semisolid and liquid formulations of pharmaceuticals is an essential step in the drug development and preclinical process. As part of characterization, methods are developed to confirm the amount of active pharmaceutical ingredients (APIs), vehicle, and other excipients in the dosing formulation, as well as formulation homogeneity, stability, purity, and content analysis.
KCAS has built capabilities around a team solely focused on dose formulation analysis providing a dedicated resource for your projects. This helps the team function as a stand-alone entity and emphasizes taking a non-bioanalytical approach to dose form analysis. For most of our projects, the analytical challenges do not come from a need for sensitivity, so our workhorse in the lab is the Shimadzu Nexera X2 UHPLC system equipped with diode array UV-VIS and fluorescence detection. We can readily adapt existing assays or develop new HPLC methods from scratch. Validations and sample analyses are performed according to Good Laboratory Practices, as one of our deliverables is a compliance statement in reports regarding adherence to GLP Principles.
Our standard approach is to gear our assays to the lowest dose. Knowing the required sensitivity enables us to set the analytical range to cover all formulation doses. We run three-point calibration curves over a narrow range, typically 50% above and 50% below target concentration.
We routinely perform In-Use Stability Studies to characterize the test material from formulation preparation, storage, and dosing until analysis. This covers test article stability for all preclinical activities over the study timeline. Stability assessments at each time point include testing formulations for concentration, pH, and appearance. In-Use Stability benchmarks your formulation stability in all container types under actual study storage conditions (room temperature, refrigerated, and frozen) for durations relevant to your study.
Chromatographic separation is key to success, particularly if your target analyte is administered in the presence of much higher concentration excipients. We pivot between reversed-phase chromatography and size exclusion chromatography depending on whether your need is for small or large molecule determination. We routinely develop GLP methods for formulations containing multiple analytes. Also, if stereoisomers are part of the formulation, regulatory agencies now require each enantiomer to be separated and studied individually, so our extensive experience with chiral separations means we can readily develop robust assays.
KCAS’s philosophy is to be flexible with technology when the assay demands require an alternative approach. All our scientists are in one facility, so it is easy to supplement our core dose form team with other analysts should a separate technology be more applicable to the problem at hand. We have implemented MS/MS and fluorescence detection for dose form analysis to provide higher sensitivity when the administered dose is low, such as highly potent compounds. Our approach mimics bioanalysis to ensure tighter acceptance criteria that we routinely expect from HPLC-UV analyses are met. An alternative approach that we have taken for large molecule dose formulation analysis has been to adapt an existing PK assay and prove it applies to dose formulations. There are challenges to this approach. Vehicle constituents may impact results, and the non-proteinaceous environment may need to be adapted during dilution steps.
In today’s fast-paced drug development environment, it is essential to have things done right the first time. Partner with KCAS and our customer-focused expert teams to deliver validated dose formulation analyses that exceed your expectations. Visit our facility and take your GLP dose formulation research to the next level.
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