The Influence of Drugs Solubilities and Chitosan-TPP Formulation Parameters on the Mean Hydrodynamic Diameters and...

Chitosan is a natural, biocompatible polymer. The aim of this work was to study the influence of drug solubility in 2% v/v acetic acid, formulation parameters, on mean hydrodynamic (MHD) diameters and drug entrapment efficiencies (% EE) into chitosan-TPP nanoparticles (NPs). Drugs of different aqueous solubilities with nearly similar molecular weights were chosen and admixed at several concentrations in 2% acetic acid at different chitosan concentrations and at fixed chitosan to TPP concentrations/volumes ratios. The NPs were freeze-dried, and the supernatants were utilized to determine % EE. Theophylline- and antipyrine-loaded NPs showed the best short-term physical stability in terms of MHD diameters. Antipyrine-loaded NPs possessed the larger MHD diameters, while vitamin C-loaded NPs showed the smallest ones. The relationships between the ratio of drug concentration relative to their solubilities in acetic acid were almost linear for antipyrine and vitamin C-loaded NPs when plotted against and the MHD diameters of NPs, and linear for antipyrine- and theophylline-loaded NPs when plotted against % EE with antipyrine NPs possessing the highest % EE. However, vitamin C- and propylthiouracil-loaded NPs exhibited curvilinear patterns with comparatively lower % EE. The concentration of chitosan, drug solubility in dispersion medium, and the ratio of the concentration of admixed drug relative to its solubility in dispersion medium were found critical in determining % EE and MHD diameters of NPs. It was evident that drugs with extremely low or high solubilities in dispersion medium resulted in low % EE when admixed at both low and high concentrations.