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By Yasuhiro Tsume

Yasuhiro TsumeIn vitro drug dissolution methodology is easy, fast, and cost effective compared to in vivo drug dissolution methodology. Current in vitro dissolution methods are mainly suitable for quality control of oral drug products but not suitable for the prediction of in vivo dissolution for most oral drug products.

Recently, oral in vivo predictive dissolution (IPD) methodology was developed to ensure in vivo performance of oral drug products. This new field has been gathering tremendous attention and interest because there are many ways to optimize the in vivo performance of oral drug products and confirm in vivo oral drug performance. In vitro bioequivalence methods aiming for biowaiver certainly is one such application. IPD methodologies usually reflect the in vivo condition such as changes of pH environment (gastric pH to intestinal pH) and drug permeation into the intestinal membrane. The in vitro dissolution results of IPD methodologies provide the extra information for oral test compounds of in vivo dissolution. Although oral IPD methodologies certainly help the development of oral drug products, there are public perception issues, e.g., consumers not accepting the concept of in vitro results to ensure in vivo performance of oral drug products, from drug discovery to regulation, involved in the potential use of this developing science.

Movement away from the in vitro dissolution method of a one-fits-all oral drug product to the in vivo predictive / in vitro dissolution method in science is almost certain. The ORBITO (oral biopharmaceutics tools) project, established in Europe in 2012, started with large groups of industries and academia to facilitate and speed up the formulation development process and to create new laboratory tests and computer models to predict better drug performance in patients. One of ORBITO’s main projects is to improve the fundamental knowledge of the gastrointestinal environment and the understanding of the gastrointestinal absorption process to deliver biopharmaceutical tools to accurately predict in vivo performance. Oral IPD methodology clearly meets this goal. The usage of oral IPD methodology is already happening in Europe, and this movement is slowly occurring in the United States, where the first guideline for oral IPD methodologies will likely be discussed and issued sometime this year or the next. I am personally interested in observing where this movement will go from here and how practical methodologies will be developed.

The In Vivo Predictive Dissolution Conference will be held on August 4–6, 2014, at University of Michigan, Ann Arbor, Michigan, where oral IPD methodologies, practical applications, and more will be discussed.

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.