Dr. Nikunj Patel is a senior director of PBPK Consultancy Services in the Simcyp division of Certara. Nikunj helps clients with advanced PBPK modeling to expedite internal decision making, support biowaivers via virtual bioequivalence assessments, and develop model-informed regulatory strategies for novel products, generic formulations, scale-up and post-approval changes (SUPAC), and justification of dissolution specifications. He has more than more 13 years’ experience in computer-aided drug design and PKPD modeling, including 10+ years’ experience focusing on PBPK modeling.

Nikunj Patel

Biosimulation (a term that includes model informed drug discovery and development) uses computer-based mathematical simulations derived from preclinical and clinical data to replicate biological processes, dynamics, and systems (1). By integrating and quantifying information about the drug, disease, how the drug affects the human body (pharmacokinetics [PK]), and how the body responds to the drug (pharmacodynamics), biosimulation optimizes decision-making. Used in most novel drug development programs today, it can predict clinical outcomes, inform clinical trial design, support evidence of effectiveness, and improve safety profiles by predicting drug–drug interactions (DDIs), and optimizing dosing. Biosimulation, which accelerates drug development, is actively used across the industry, and encouraged by FDA and other global regulators.

In the context of formulation development, a key biosimulation approach, termed model informed formulation development (MIFD), is used to determine the 

 correlation and/or extrapolation (IVIVC/IVIVE), a predictive mathematical model describing the relationship between an 

 PK or response. IVIVC is used to establish a predictive relationship between 

 drug absorption. IVIVC can be numerically based, for drugs with a simpler, often linear relationship between absorption and dissolution, or mechanistically based (also called physiologically based pharmacokinetics modeling, or PBPK), for more complex products.

Advancing Oral Drug Development Using MIFD

Based on decades of data and advancements in mathematical modeling, currently available PBPK models can help simulate the transit, disintegration, dissolution, precipitation, and absorption of drug from a particular formulation and include population variability. Moreover, PBPK models can help evaluate the fate of a formulation in different prandial states such as fasted vs fed conditions, in a pediatric vs adult gastrointestinal (GI) tract, in subjects with achlorhydria, etc. PBPK models can also help assess and optimize the role of excipients on drug solubility, dissolution, and absorption, evaluate the salt selection and solid-state polymorphism, enabling formulations to be examined under 

 conditions without performing clinical studies.

Pharmaceutical Technology’s October 2023 Trends in Formulation eBook

is senior director of PBPK Consultancy Services, 

 is senior vice president and chief commercial officer, both at the Simcyp division of Certara

When referring to this article, please cite it as Patel, N.; Leinfuss, E. Advancing Oral Drug Development Using MIFD. 

Pharmaceutical Technology’s Trends in Formulation eBook 

Articles

Model informed formulation development uses in-silico modeling and simulation to identify and/or refine promising formulations faster and cheaper, support formulation strategy and increasingly, demonstrate virtual bioequivalence and obtain biowaivers.