Dissolution of Formulated Poorly Water-soluble Pharmaceutical

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].

The 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:

(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.