Authors: Manthena V.S. Varma; Sateesh Khandavilli; Yasvanth Ashokraj; Amit Jain; Anandbabu Dhanikula; Anurag Sood; Narisetty S. Thomas; Omathanu Pillai; Pradeep Sharma; Rajesh Gandhi; Shrutidevi Agrawal; Vinod Nair; Ramesh Panchagnula

Source: Current Drug Metabolism, Volume 5, Number 5, October 2004 , pp. 375-388(14)

Publisher: Bentham Science Publishers

Abstract:

The tenets of biopharmaceutics, solubility and permeability, are of pivotal importance in new drug discovery and lead optimization due to the dependence of drug absorption and pharmacokinetics on these two properties. A classification system for drugs based on these two fundamental parameters, Biopharmaceutic Classification System (BCS), provides drug designer an opportunity to manipulate structure or physicochemical properties of lead candidates so as to achieve better “deliverability”. Considering the facts for failure of NCEs, drug research, once concentrating on optimizing the efficacy and safety of the leads, dramatically transformed in the past two decades. With the enormous number of molecules being synthesized using combinatorial and parallel synthesis, high throughput methodologies for screening solubility and permeability has gained significant interest in pharmaceutical industry. Ultimate aim of the drug discovery scientist in pharmacokinetic optimization is to tailor the molecules so that they show the features of BCS class I without compromising on pharmacodynamics. Considerations to optimize drug delivery and pharmacokinetics right from the initial stages of drug design propelled need for “High Throughput Pharmaceutics” (HTP). In silico predictions and development of theoretical profiles for solubility and lipophilicity provides structure based biopharmaceutical optimization, while in vitro experimental models (microtitre plate assays and cell cultures) validate the predictions. Thus, biopharmaceutical characterization during drug design and early development helps in early withdrawal of molecules with insurmountable developmental problems associated with pharmacokinetic optimization.

Keywords: Biopharmaceutic; silico predictions; microtitre plate

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389200043335423

Affiliations: 1: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Phase X, SAS Nagar, Punjab 160062, India.

Publication date: 2004-10-01

More about this publication?

• Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:
  
  In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.

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• By this author: Manthena V.S. Varma ;  Sateesh Khandavilli ;  Yasvanth Ashokraj ;  Amit Jain ;  Anandbabu Dhanikula ;  Anurag Sood ;  Narisetty S. Thomas ;  Omathanu Pillai ;  Pradeep Sharma ;  Rajesh Gandhi ;  Shrutidevi Agrawal ;  Vinod Nair ;  Ramesh Panchagnula

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