Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 345, Issue 1-2, Pages 142-153Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2007.05.039
Keywords
PAMAM dendrimer; furosemide; complexation; ionization; solubility; release
Categories
Ask authors/readers for more resources
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, an-tide 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 (
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available