Development of NovelIn SilicoModel to Predict Corneal Permeability for Congeneric Drugs: A QSPR Approach

Abstract

This study was undertaken to determinein vivopermeability coefficients for fluoroquinolones and to assess its correlation with the permeability derived using reported models in the literature. Further, the aim was to develop novel QSPR model to predict corneal permeability for fluoroquinolones and test its suitability on other training sets. Thein vivopermeability coefficient was determined using cassette dosing (N-in-One) approach for nine fluoroquinolones (norfloxacin, ciprofloxacin, lomefloxacin, ofloxacin, levofloxacin, sparfloxacin, pefloxacin, gatifloxacin, and moxifloxacin) in rabbits. The correlation between corneal permeability derived usingin vivostudies with that derived from reported models was determined. Novel QSPR-based model was developed usingin vivocorneal permeability along with other molecular descriptors. The suitability of developed model was tested onβ-blockers (n=15). The model showed better prediction of corneal permeability for fluoroquinolones(r2>0.9)as well asβ-blockers(r2>0.6). The newly developed QSPR model based uponin vivogenerated data was found suitable to predict corneal permeability for fluoroquinolones as well as other sets of compounds.