Rational formulation strategy from drug discovery profiling to human proof of concept

Abstract

The objective of this paper is to introduce some strategic guidance to a rational formulation strategy of new molecules as oral dosage forms, based on a sound scientific understanding of factors determining the oral bioavailability. The critical implication of permeability and solubility is discussed along with the efficient dose of the drug. The concept of dose-solubility number is introduced as a tool for chemists to assess the develop-ability of different molecules very early during discovery stage. Based on this understanding, a rational formulation strategy for preclinical and early clinical phases is provided. The technical considerations and limitations of different formulation technologies are discussed and illustrated via concrete examples. This approach has the advantage of streamlining the formulation process in order to avoid delaying the development of new drugs due to formulation related issues.

Keywords: Formulation development; oral drug delivery; pre-formulation; solid dispersion; solubility enhancement.