The effect of PAMAM dendrimer generation size and surface functional group on the aqueous solubility of nifedipine

The aim of this study was to investigate the effect of low generation (G0-G3) ethylenediamine (EDA) core poly(amidoamine) (PAMAM) dendrimers on the aqueous solubility of nifedipine.-The aqueous solubility of nifedipine was measured in the presence of dendrimers at 30degreesC in Tris buffers at pH 4, 7, and 10 using the traditional rotary bottle method. Results showed that generation size, surface functional group and the pH of the aqueous media determined the aqueous solubility of nifedipine and that solubility profiles were of the Higuchi A(L)-type. Both amine and ester terminated dendrimers caused the highest increase in nifedipine solubility at pH 7. The order in which the dendrimers increased the solubility at pH 7 was G2.5 > G3 > G1.5 > G2 > GO.5 > G1 > G0. In addition, at each pH, the solubility of nifedipine was greater in the presence of ester-terminated dendrimers compared to the amine-terminated dendrimers possessing the same number of surface functional groups. The pH and surface functional group dependent increase in nifedipine solubility caused by the dendrimers was likely due to changes in the degree of protonation of the dendrimers. A decrease in the protonation of dendritric amines was expected to promote hydrogen bond formation between the tertiary amines within the dendrimer cavity and the nifedipine molecule. (C) 2004 Elsevier B.V. All rights reserved.