Improved entrapment efficiency of hydrophilic drug substance during nanoprecipitation of poly(l)lactide nanoparticles.

The purpose of this research was to improve the entrapment efficiency of a model hydrophilic drug substance, sodium cromoglycate, loaded inside polylactic acid nanoparticles by a modified nanoprecipitation method. The effect of formulation parameters was studied to improve the entrapment efficiency of the drug substance inside the nanoparticles. Several parameters (changes in the amount of model drug, solvent selection, electrolyte addition, pH alteration) were tested in order to increase the loading of the hydrophilic drug in the hydrophobic nanoparticles. Lowering of the pH was the most efficient way to increase the drug loading; up to approximately 70% of the sodium cromoglycate used in the particle formation process could be loaded inside the particles. The loading efficiency without the pH change was around 10% to 15% at maximum. The crystallinity values and crystal habits of the sodium cromoglycate nanoparticles were studied (x-ray diffraction) before and after the lowering of the pH. The change in pH conditions during the nanoprecipitation process did not affect markedly the crystallinity properties of the drug substance. According to this study, it is possible to improve the entrapment efficiency of hydrophilic sodium cromoglycate inside of the nanoparticles by small changes in the process parameters without alterations in the physical properties of the original drug substance.