IVIVC of the Product

During the total process of drug development, formulation optimization represents a critical aspect to ensure the quality of pharmaceutical products. However, the formulation optimization is always a complex and time consuming procedure that generally requires alteration in composition, excipients, batch sizes and manufacturing parameters. Moreover, the composition or other characteristic changes of the formulation may lead to a change of in vivo pharmacokinetics. Therefore, a corresponding bioequivalence study is required to be done for proving the similarity of the new formulation. The in vitro- in vivo correlations (IVIVC) represents the mathematical relationship between an in vitro property of the formulation (the in vitro release data of a dosage form) and its in vivo act (generally reflected by the time course of the plasma concentration of API). In this case, a comprehensive understanding of the correlations between in vitro and in vivo data are of great importance to the drug development and optimization of formulation, since it can significantly reduce the research time and expenditure.

BOC Sciences has a wealth of expertise in formulation development and analysis of products for quality control. Our experts are well aware of that a good correlation is a very useful tool for predicting in vivo results based on the in vitro data and allows dosage form optimization with the fewest possible trials in mankind. Generally, based on the ability of the correlation to reflect the complete plasma drug level-time profile, there are four levels of IVIVC (levels A, B, C, and multiple C) according to the description of FDA.

• Level A: Level A is the highest category of correlation and the most preferred to achieve, since it correlates the entire in vitro and in vivo profiles and allows bio waiver for changes in manufacturing and minor changes in formulation.
• Level B: The in vitro data from level B can’t be utilized to completely reflect the actual in vivo plasma level curves and justify the extremes of quality control standards.
• Level C: As the weakest level of correlation, there is some obvious limitations for the usefulness of such grade in predicting in vivo drug performance. Although it does not reflect the complete shape of plasma drug concentration time curve, level C correlation can be useful in the early stages of formulation.
• Multiple Level C: Multiple level C correlation is the relationship between one or more pharmacokinetic parameters, such as Cmax and AUC, and amount of drug dissolved at several time point of dissolution profile.

BOC Sciences has a team of experts who are professional in formulation development and product quality control. We work cooperatively with our customers to analysis their pharmaceutical products in a highly efficient and rapid way. By conducting a comprehensive IVIVC investigation, clients can benefit from a lot, including:

• Efficient and rapid drug formulation optimization
• Justification for therapeutic product quality
• Time and cost saving for their product development
• Provide a surrogate for in vivo bioequivalence and to support biowaivers

References

1. Sakore, S. and Chakraborty, B. (2011) ‘In Vitro–In Vivo Correlation (IVIVC): A Strategic Tool in Drug Development’, J Bioequiv Availab, S3.
2. Cardot, J. M., Beyssac, E. and Alric, M. (2007) ‘In vitro-in vivo correlation: importance of dissolution in IVIVC’, Dissolution technologies, 14(1): 15.