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Prof. Dr. Ing. Yuanhui Ji

Prof. Dr. Ing. Yuanhui Ji Foto von Prof. Dr. Ing. Yuanhui Ji keine E-Mail

Dissolution of Formulated Poorly Water-soluble Pharmaceutical

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Abstract:

The development of potentially efficacious pharmaceuticals is hindered by their poor aqueous solubilities which result in a poor bioavailability. Our research focus on the dissolution mechanism and rate of formulated poorly water-soluble pharmaceuticals in solutions with experiments and theoretical modeling. It is expected that the research could provide useful knowledge for the formulation strategy development of poorly water-soluble amorphous pharmaceuticals.




Description:

It is known that the development of potentially efficacious pharmaceuticals is hindered by their poor aqueous solubilities which result in a poor bioavailability [1]. Amorphous pharmaceuticals hold potential to enhance the dissolution rate for poorly water-soluble pharmaceutical candidates [2]. In recent years, several investigations on the amorphous forms of active pharmaceutical ingredients (APIs) formulated in various polymer carriers to improve their dissolution have been reported. Characterizing the pharmaceutical-dissolution mechanism to measure product performance is particularly important for rationally designing optimal formulations of poorly soluble compounds [3].

Picture-1-for-homepage_Yuanhui-JiThe pharmaceutical dissolution kinetics of formulated poorly water-soluble amorphous pharmaceuticals has been widely investigated. However, it is difficult to obtain the dissolution rate-controlling step just from the experimental dissolution kinetics curve and empirical model of the dissolution. Therefore, in this research, the dissolution kinetics of the poorly water-soluble pharmaceutical is analyzed with both experimental measurements and modeling in which the mass transport of the dissolved pharmaceutical at the solid-solution interface is described.

To achieve this objective, the following investigations are performed:Picture-2-for-homepage_Yuanhui-Ji

(a) to prepare the amorphous solid dispersions of pharmaceutical;

(b) to measure the solubility of pharmaceutical in aqueous systems;

(c) to determine the dissolution kinetics of the pharmaceutical experimentally;

(d) to investigate the dissolution mechanism with theoretical modeling in which the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT)

Equation of State [4] will be used to represent the thermodynamic properties of the system.

It is expected that the research could provide useful knowledge for the formulation strategy development of poorly water-soluble amorphous pharmaceuticals.

Picture 3 for homepage_Yuanhui Ji



References:

[1] M. Kennedy, J. Hu, P. Gao, L. Li, A. Ali-Reynolds, B. Chal, V. Gupta, C. Ma, N. Mahajan, A. Akrami, and S. Surapaneni:

"Enhanced Bioavaolability of a Poorly Soluble VR1 Antagonist Using an Amorphous Solid Dispersion Approach: A Case Study"

Molecular Pharmaceutics, vol. 5, pp. 981-993, 2008


[2] D. Zhou, G. G. Z. Zhang, D. Law, D. J. W. Grant, and E. A. Schmitt:

"Thermodynamics, Molecular Mobility and Crystallization Kinetics of Amorphous Griseofulvin"

Molecular Pharmaceutics, vol. 5, pp. 927-936, 2008


[3] C. K. Brown, H. P. Chokshi, B. Nickerson, R. A. Reed, B. R. Rohrs, and P. A. Shah:

"Acceptable Analytical Practices for Dissolution Testing of Poorly Soluble Compounds"

Pharmaceutical Technology, December, pp. 56-65, 2004


[4] M. Kleiner, F. Tumakaka, and G. Sadowski:

"Thermodynamic Modeling of Complex Systems"

Structure and Bonding, Springer-Verlag Berlin Heidelberg, vol. 131, pp. 75-104, 2009



Selected Publications:

[1] Y. H. Ji, W. J. Huang, X. H. Lu, Z. H. Yang, and X. Feng:

"Theoretical limiting concentration for mineralization of trichloromethane and dichloromethane in aqueous solutions by AOPs",

SCIENCE CHINA Chemistry, vol. 54, pp. 559-564, 2011


[2] X. H. Lu, Y. H. Ji, and H. L. Liu:

"Non-equilibrium thermodynamics analysis and its application in interfacial mass transfer",

SCIENCE CHINA Chemistry, vol. 54, pp. 1659-1666, 2011


[3] Y. H. Ji, X. Y. Ji, C. Liu, X. Feng, and X. H. Lu:

"Modelling of mass transfer coupling with crystallization kinetics in microscale"

Chemical Engineering Science, vol. 65, pp. 2649-2655, 2010


[4] Y. H. Ji, W. J. Huang, X. H. Lu, X. Feng, and Z. H. Yang:

"Theoretical limit of energy consumption for removal of organic contaminants in U.S. EPA Priority Pollutant List by NRTL, UNIQUAC and Wilson models"

Fluid Phase Equilibria, vol. 297, pp. 210-214, 2010


[5] Y. H. Ji, X. H. Lu, Z. H. Yang, and X. Feng:

"Thermodynamic analysis on the theoretical energy consumption in the removal of organic contaminants by physical methods"

SCIENCE CHINA Chemistry, vol. 53, pp. 671-676, 2010


[6] W. J. Huang, Y. H. Ji, Z. H. Yang, X. Feng, C. Liu, Y. H. Zhu, and X. H. Lu:

"Mineralization of trace nitro/chloro/methyl/amino-aromatic contaminants in wastewaters by advanced oxidation processes", Industrial & Engineering Chemistry Research, vol. 49, pp. 6243-6249, 2010


[7] Y. H. Ji, Z. H. Yang, X. Y. Ji, X. Feng, W. J. Huang, C. Liu, W. Li, and X. H. Lu:

"Thermodynamic analysis on the mineralization of trace organic contaminants with oxidants in advanced oxidation processes", Industrial & Engineering Chemistry Research, vol. 48, pp. 10728-10733, 2009


[8] Y. H. Ji, Z. H. Yang, X. Y. Ji, W. J. Huang, X. Feng, C. Liu, L. H. Lu, and X. H. Lu:

"Thermodynamic study on the reactivity of trace organic contaminant with the hydroxyl radicals in waters by advanced oxidation processes"

Fluid Phase Equilibria, vol. 277, pp. 15-19, 2009


[9] C. Liu, Y. H. Ji, Q. Shao, X. Feng, and X. H. Lu:

"Thermodynamic analysis for synthesis of advanced materials"

Structure and Bonding, Springer-Verlag Berlin Heidelberg, vol. 131, pp. 193-270, 2009


[10] Y. H. Ji, X. Y. Ji, X. Feng, C. Liu, L. H. Lu, and X. H. Lu:

"Progress in the study on the phase equilibria of the CO2-H2O and CO2-H2O-NaCl systems"

The Chinese Journal of Chemical Engineering, vol. 15, pp. 439-448, 2007


[11] C. Liu, Y. H. Ji, Y. Bai, F. Q. Cheng, and X. H. Lu:

"Formation of porous crystals by coupling of dissolution and nucleation process in fractional crystallization"

Fluid Phase Equilibria, vol. 261, pp. 300-305, 2007