Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability

Authors

  • Parvin Zakeri-Milani Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Zohreh Fasihi Biotechnology Research Center and Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Jafar Akbari Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  • Ensieh Jannatabadi Biotechnology Research Center and Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Mohammad Barzegar-Jalali Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Raimar Loebenberg Faculty of Pharmacy and Pharmaceutical Science, University of Alberta, Edmonton, Alberta, Canada. http://orcid.org/0000-0002-0919-0213
  • Hadi Valizadeh Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. http://orcid.org/0000-0003-4157-6279

DOI:

https://doi.org/10.18433/J3KS4P

Abstract

Background: We assessed the feasibility of using crystal-liquid fugacity ratio (CLFR) as an alternative parameter for intestinal permeability in the biopharmaceutical classification (BCS) of passively absorbed drugs. Methods: Dose number, fraction of dose absorbed, intestinal permeability, and intrinsic dissolution rate were used as the input parameters. CLFR was determined using thermodynamic parameters i.e., melting point, molar fusion enthalpy, and entropy of drug molecules obtained using differential scanning calorimetry. Results: The CLFR values were in the range of 0.06-41.76 mole percent. There was a close relationship between CLFR and in vivo intestinal permeability (r > 0.8). CLFR values of greater than 2 mole percent corresponded to complete intestinal absorption. Applying CLFR versus dose number or intrinsic dissolution rate, more than 92% of tested drugs were correctly classified with respect to the reported classification system on the basis of human intestinal permeability and solubility. Conclusion: This investigation revealed that the CLFR might be an appropriate parameter for quantitative biopharmaceutical classification. This could be attributed to the fact that CLFR could be a measure of solubility of compounds in lipid bilayer which was found in this study to be directly proportional to the intestinal permeability of compounds. This classification enables researchers to define characteristics for intestinal absorption of all four BCS drug classes using suitable cutoff points for both intrinsic dissolution rate and crystal-liquid fugacity ratio. Therefore, it may be used as a surrogate for permeability studies.

 

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Published

2016-08-18

How to Cite

Zakeri-Milani, P., Fasihi, Z., Akbari, J., Jannatabadi, E., Barzegar-Jalali, M., Loebenberg, R., & Valizadeh, H. (2016). Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability. Journal of Pharmacy & Pharmaceutical Sciences, 19(3), 312–324. https://doi.org/10.18433/J3KS4P

Issue

Section

Pharmaceutical Sciences; Review Articles