Effect of pH on the solubility and release of furosemide from polyamidoamine (PAMAM) dendrimer complexes.

The complexation of the practically insoluble drug furosemide (acidic pK(a) 3.22) with lower generation PAMAM dendrimers showed a significant release dependence on the ionization state of the drug. UV and FTIR studies suggested that the drug was localized in the interior of the dendrimer. The dendrimer amine, amide and ester groups, demonstrated pH-dependent ionization as did the drug carboxylic acid group and it was proven that the most efficient drug complexation was achieved in slightly acidic conditions (pH 4.0-6.0). At this pH, amide groups in the dendrimer cavities were at least partially ionized to expose a positive charge whilst the furosemide carboxylic acid ionized to great extent (pH>pK(a)) resulting in electrostatic complexation. Conversely, higher release rates were observed in acidic conditions (pH 1.2) where furosemide was virtually unionized, emphasizing the importance of the drug ionization state in the determination of drug release. Despite the complex interactions between the dendrimer and drug and its effects on release kinetics, the dendrimers resulted in higher solubility of the drug and contributed significantly to the array of available techniques to increase the solubility of poorly water-soluble drugs that are very abundant in industry today. Complexation with low generation PAMAM dendrimers (

Effect of polyamidoamine (PAMAM) dendrimers on the in vitro release of water-insoluble nifedipine from aqueous gels.

The objective of this study was to determine the effect of ethylenediamine core PAMAM dendrimers on the release of nifedipine suspended in aqueous gels and to correlate release to the increase in solubility afforded by the dendrimers. Drug release from aqueous 5% HPMC gels containing nifedipine (2% wt/vol) through 0.2-microm membranes was measured using Enhancer cells and 50% ethanolic solution as the receptor medium. The release from gels containing PAMAM G-3 and G-5 (0.25%-1% wt/vol) was compared with gels containing the cosolvent isopropyl alcohol (10%-80% vol/vol). PAMAM dendrimers significantly increased the solubility of nifedipine. This caused a significant increase in the release rate of nifedipine from the gel suspensions. The increase in drug release depended on the concentration and generation size of the dendrimers added. For higher generations (G-5) lower concentrations were needed to obtain equivalent increases in release. Although the increase in solubility and release was not as high as from gels containing high concentrations of the cosolvent isopropyl alcohol, the dendrimers prevented the recrystallization of the drug that was observed when the gels containing isopropyl alcohol were left open.

Comparison of the aqueous solubilization of practically insoluble niclosamide by polyamidoamine (PAMAM) dendrimers and cyclodextrins.

This study is the first report of the solubilization of niclosamide by cyclodextrin complexation or the interaction between the drug and polyamidoamine (PAMAM) dendrimers. Half generation dendrimers with more polar carboxylate surface functional groups did not increase the solubility of niclosamide. From the phase solubility studies, when the fold enhancement in solubility of niclosamide combined with full generation amine terminated PAMAM dendrimers was compared with that obtained when the drug was combined with beta- or hydroxypropyl-beta-cyclodextrin, the results showed that, except for G-0 dendrimer at pH 7, the solubility of niclosamide was significantly higher in the presence of the dendrimers. In addition, higher equilibrium stability constants and complexation efficiency showed that the dendrimers formed stronger more stable complexes than the CDs. However, the strong interaction between the amine surface functional groups and the niclosamide molecule complexes caused a decrease in dissolution rate compared to the CDs because the interaction retarded the release of the drug from the dendrimers. In addition to increasing the solubility, PAMAM dendrimers therefore also offer the possible for the controlled release of the drug from solid dosage forms.

The relationship between surface adsorption and the hydrolysis of amitraz in anionic surfactant solutions.

The adsorption of amitraz to various adsorbents was studied in terms of the amount and rate of adsorption and the effect that adsorption had on the stability of amitraz in an aqueous environment. Adsorption results showed that in terms of their ability to adsorb amitraz from solution the adsorbents tested in this study can be ordered as follows: coarse carbon > cation exchange resin > or = anion exchange resin > fine carbon. Amitraz was not adsorbed on sand and potassium oxihumate. Adding sodium lauryl sulfate and potassium oxihumate to aqueous suspensions of suspended adsorbents containing adsorbed amitraz showed that both these anionic surfactants significantly increased the hydrolysis rate because the half-lives for amitraz was reduced from 27 days for a suspension to only 8 hours for amitraz adsorbed to a cation exchange resin and suspended in an aqueous buffer pH 5.8 containing 0.5% of the anionic surfactant sodium lauryl sulfate and 12 hours when 1% potassium oxihumate was added.

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 30 degrees C 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 AL-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 > or = G0.5 > 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.