Provisional in-silico biopharmaceutics classification (BCS) to guide oral drug product development

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The main objective of this work was to investigate in-silico predictions of physicochemical properties, in order to guide oral drug development by provisional biopharmaceutics classification system (BCS). Four in-silico methods were used to estimate LogP: group contribution (CLogP) using two different software programs, atom contribution (ALogP), and element contribution (KLogP). The correlations (r2) of CLogP, ALogP and KLogP versus measured LogP data were 0.97, 0.82, and 0.71, respectively. The classification of drugs with reported intestinal permeability in humans was correct for 64.3%–72.4% of the 29 drugs on the dataset, and for 81.82%–90.91% of the 22 drugs that are passively absorbed using the different in-silico algorithms. Similar permeability classification was obtained with the various in-silico methods. The in-silico calculations, along with experimental melting points, were then incorporated into a thermodynamic equation for solubility estimations that largely matched the reference solubility values. It was revealed that the effect of melting point on the solubility is minor compared to the partition coefficient, and an average melting point (162.7°C) could replace the experimental values, with similar results. The in-silico methods classified 20.76% (±3.07%) as Class 1, 41.51% (±3.32%) as Class 2, 30.49% (±4.47%) as Class 3, and 6.27% (±4.39%) as Class 4. In conclusion, in-silico methods can be used for BCS classification of drugs in early development, from merely their molecular formula and without foreknowledge of their chemical structure, which will allow for the improved selection, engineering, and developability of candidates. These in-silico methods could enhance success rates, reduce costs, and accelerate oral drug products development.

Original languageEnglish
Pages (from-to)1563-1575
Number of pages13
JournalDrug Design, Development and Therapy
Volume8
DOIs
StatePublished - 24 Sep 2014

Keywords

  • Biopharmaceutics classification system
  • In-silico
  • Intestinal permeability
  • Partition coefficient
  • Solubility

Fingerprint

Dive into the research topics of 'Provisional in-silico biopharmaceutics classification (BCS) to guide oral drug product development'. Together they form a unique fingerprint.

Cite this