Pharmaceutical organogels prepared from aromatic amino acid derivatives.
Organogels are semi-solid systems in which an organic liquid phase is immobilized by a 3-dimensional network composed of self-assembled gelator molecules. Although there is a large variety of organogel systems, relatively few have been investigated in the field of drug delivery, owing mostly to the lack of information on their biocompatibility and toxicity. In this work, organogelator-biocompatible structures based on aromatic amino acids, namely, tyrosine, tryptophan, and phenylalanine were synthesized by derivatization with aliphatic chains. Their ability to gel an injectable vegetable oil (i.e.safflower oil) and to sustain the release of a model anti-Alzheimer drug (i.e.rivastigmine) was then evaluated. Organogels and molecular packing were characterized by differential scanning calorimetry, rheology analysis, Fourier-transform infrared spectroscopy and X-ray crystallography. The amino acid derivatives were able to gel safflower oil through van der Waals interactions and H-bonds. Tyrosine-derivatives produced the strongest gels while tryptophan was associated with poor gelling properties. The superior gelling ability of tyrosine derivatives could be explained by their well-structured 2-dimensional packing in the network. The addition of an optimalN-methyl-2-pyrrolidone amount to tyrosine gels fluidized the network and allowed their injection through conventional needles. Upon contact with an aqueous medium, the gels formedin situand released entrapped rivastigmine in a sustained fashion.
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, QC, Canada H3C 3J7.
Guillaume
G
Bastiat
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, QC, Canada H3C 3J7; Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, Switzerland. ; Tel: +41 (0) 44 633 7310.
Jean-Christophe
JC
Leroux