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By Yasuhiro Tsume

Compendial in vitro dissolution methodologies such as USP I and II have been conducted to assure the quality of oral products and to perform the in vivo-in vitro correlation as well as predict in vivo drug dissolution of test oral products. However, the human gastrointestinal (GI) tract is far more complicated than the simplified compendial dissolution apparatuses. As a result, newer in vitro dissolution methodologies have to be developed in order to understand the in vivo performance of oral (test) formulations and to formulate the best oral products.

Researchers have been conducting the different dissolution methodologies, in vivo predictive dissolution (iPD) methodologies, to evaluate the in vivo performance of their oral formulations.   Lately, the use of in vitro dissolution methodology to predict and develop oral dosage forms, iPD, or formulation predictive dissolution methodology has been an area of focus to ensure in vivo performance of oral drug products, as well as bioequivalence in the formulation development. This new field has been gathering tremendous attention and interest from industry, academia, and regulatory agencies. Successful predictions and simulations by in vitro and in silico methodologies will speed up the development of any oral drug products. Eventually it will also reduce the cost of oral products entering the market, leading to the fewer clinical studies and cheaper drug products. There are many ways in vivo predictive and formulation predictive dissolution methodologies optimize and assure the in vivo dissolution of oral drug products for therapeutic effect and safety and to ensure in vivo oral drug equivalent performance, including Scale-Up and Post-Approval Changes. Bioequivalence study certainly is one of the prominent applications of this type of in vitro dissolution methodology.

In Europe the Innovative Tools for Oral Biopharmaceutics (OrBiTo) has formed large groups of industries and academic institutions to facilitate and speed up the formulation development process. One of the main projects was to improve the fundamental knowledge of the GI environment and the understanding of the GI absorption process to deliver biopharmaceutical tools to accurately predict in vivo performance of oral drug products. OrBiTo has been creating new laboratory/dissolution tests and computer models to predict better drug performance in patients in Europe since 2012. This was clearly the set-up to develop newer dissolution methods for predicting in vivo oral drug performance. Through the OrBito project and scientific advancements, more researchers in the industry and academia have become interested in the mechanical/science-based dissolution settings and approaches to predict better in vivo performance of oral products. Those dissolution methodologies certainly help the development of oral drug products. However, these developments­­—drug discovery, development, and regulation—must overcome validation and drug safety assurance guidelines before achieving the maximum in vivo performance. Still, this type of movement is inevitable and many scientists have been searching for the best methodologies to test their formulations and to predict in vivo bioperformance of oral dosage forms.

The AAPS Workshop on In Vivo Predictive Drug Dissolution/Simulation, September 11‒12, 2017, in Rockville, Md., will be the best place to gather the information like the selection of in vitro methodologies for active pharmaceutical ingredient and physicochemical drug properties, along with clinical and nonclinical research data. Scientists who work with formulation, quality control, PK/PD, and bioequivalence, as well as those who work with the regulatory process would be interested in this workshop. Attendees will have the opportunity to learn fundamental and advanced knowledge and to discuss the best possible in vitro/in silico ways to evaluate/predict in vivo performance of oral products.

Yasuhiro Tsume, Ph.D., is a scientist at University of Michigan. He has worked in various research projects such as prodrug strategies, cancer therapeutics, in vivo predictive dissolution (IPD) methodologies, and translational studies.