Homogeneity or uniformity of a dose formulation is a requirement for ensuring integrity of regulated preclinical safety studies. Demonstrating homogeneity ensures that the preclinical dose formulation contains active ingredient(s) uniformly throughout the formulation, thereby ensuring that the test system is being administered using the appropriate amount of test material. Accurate assessment of dose formulation homogeneity is accomplished by using an appropriate sampling protocol and validated analytical methodology.
Assessing homogeneity for preclinical dose formulations is generally completed by sampling the prepared preclinical dose formulation at various strata in the formulation container. Sampling from the top, middle, and bottom followed by analysis using a validated analytical method is an example. Homogeneity is established by sampling from the initial preparation at both the lowest and highest dosing concentrations. Confirmation of homogeneity ensures that the formulation preparation procedure is adequate for the study.Homogeneity of a preclinical dose formulation can be affected by multiple factors, including, but not limited to:
Homogeneity should be reassessed when there is a significant change in the batch size. For instance, if 100 mL of a formulation are prepared for the first study and 1000 mL are prepared for a subsequent study, homogeneity is performed on both batches. These tests ensure that the formulation process at each scale yields a homogeneous mixture. The need for these two processes is based on mixing techniques, because different methods are used depending on batch size.
Once homogeneity has been established using a specific formulation procedure, it is crucial to maintain consistent methods for preparation throughout the study. Minor changes may affect the ability to prepare and maintain a homogeneous mixture.
Challenges with homogeneity can vary depending on the type of formulation. There are multiple types of dose formulations used for in vivo studies, including, solutions, suspensions, and solids as described below: