Influence of excipients on solubility and dissolution of pharmaceuticals.
In this work, solubilities and dissolution profiles of the active pharmaceutical ingredients (APIs) indomethacin and naproxen were measured in water in the presence of one excipient out of polyethylene glycol (PEG) 2000, 6000 and 12000, polyvinylpyrrolidone (PVP) K 25 and mannitol. It was found that the solubility of indomethacin and naproxen was increased with an addition of the selected excipients, which was also predicted by the perturbed-chain statistical associating fluid theory (PC-SAFT). The two-step chemical-potential-gradient model was applied to investigate the dissolution mechanism of indomethacin and naproxen in water in the presence of the excipient. It was found that the dissolution mechanisms of indomethacin and naproxen were changed by the presence of excipients. Although the solubility of the API was increased by the addition of excipients, the dissolution rate of the API was decreased in some cases. This was mainly due to the combination of the molecular interactions between the API and the polymer with the influence of the excipients on the kinetic part (rate constant of the surface reaction or diffusion of the API or both) of API dissolution as function of PEG molar mass as well as of the API type. Based upon the determined rate constants, the dissolution profiles were modeled with a high accuracy compared with the experimental data.
TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge Str. 70, D-44227 Dortmund, Germany.
Raphael
R
Paus
TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge Str. 70, D-44227 Dortmund, Germany.
Anke
A
Prudic
TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge Str. 70, D-44227 Dortmund, Germany. Electronic address: Yuanhui.Ji@bci.tu-dortmund.de.
Yuanhui
Y
Ji
D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D005079:Excipients / Q000737:chemistry*; D007213:Indomethacin / Q000737:chemistry*; D007700:Kinetics; D008353:Mannitol / Q000737:chemistry; D008956:Models, Chemical; D015233:Models, Statistical; D009288:Naproxen / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014783:Viscosity; D014867:Water / Q000737:chemistry
D005079:Excipients; D014867:Water; C000595215:Polyethylene Glycol 6000; D008353:Mannitol; D011092:Polyethylene Glycols; D009288:Naproxen; D011205:Povidone; C000595210:polyethylene glycol 2000; D007213:Indomethacin
Chemical potential gradient; Dissolution; Excipients; Indomethacin (PubChem CID: 3715); Mannitol (PubChem CID 6251); Naproxen (PubChem CID: 156391); PC-SAFT; Polyethylene glycol (PubChem CID: 174); Polyvinylpyrrolidone (PubChem CID: 6917); Poorly soluble APIs; Solubility; Thermodynamics