title: Selecting oral bioavailability enhancing formulations during drug discovery and development.
abstract: BACKGROUND
  The role of chemical structure, lipophilicity, physico-chemical, absorption, distribution, metabolism, excretion, toxicity (ADMET) and biopharmaceutical properties of compounds including bioavailability are critical in drug discovery and drug dosage forms design.
  
  
  METHODS
  The authors discuss a number of parameters including computational approaches used for selected chemical structures with biological activity for lead optimization and chemogenomics and preclinical studies for ADMET process development of ligand properties. The authors also look at a number of other parameters including: early drug product formulations with method selection based on the biopharmaceutical classification system (BCS); in vitro-in vivo correlation (IVIVC) and different formulation strategies to enhance solubility; dissolution rate and permeability; bioavailability evaluation and quality by design as an opportunity to develop 'safe space' regions, where bioavailability is unaffected by pharmaceutical variations.
  
  
  CONCLUSIONS
  The biopharmaceutical requirements for absorption are solubility and permeability. Both are influenced by lipophilicity, but in the opposite way. The genomic methodology, coupled with combinatorial chemistry, high-throughput screening, structure-based design and in silico ADMET would yield parameters as a starting point for the biopharmaceutical properties determination in further preclinical and clinical studies. Consecutive stages in drug discovery and development are irreplaceable, but pharmacokinetics is the critical step. Selection of drug formulations based on the BCS, IVIVC are the principal aspects to enhance the solubility and dissolution rate, while a rationale management of pharmaceutical and technological factors will enhance the bioavailability.
authors.affiliation: "Iuliu Hatieganu", University of Medicine and Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics , Str. Victor Babes nr.8, 400023, Cluj-Napoca , Romania +40 264575841 ; sleucuta@yahoo.com.
authors.forename: Sorin Emilian
authors.initials: SE
authors.lastname: Leucuta
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D055808:Drug Discovery; D006801:Humans; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations