In situ-forming pharmaceutical organogels based on the self-assembly of L-alanine derivatives.
OBJECTIVE
To characterize novel pharmaceutical organogels based on the self-assembly of L-alanine derivatives in hydrophobic vehicles.


METHODS
The gelation properties of N-lauroyl-L-alanine (LA) and N-lauroyl-L-alanine methyl ester (LAM) were investigated in the presence of various solvents. Gel-sol and sol-gel transitions were evaluated by the inverse flow method, and gelation kinetics were determined by turbidimetry. The in vitro release kinetics of labeled dextran physically dispersed in the oil-based organogel was assessed in phosphate-buffered saline. In situ formation of the implants was evaluated in rats by subcutaneously injecting a solution containing LAM, an oil, and a water-diffusible inhibitor of self-assembly (ethanol).


RESULTS
The LAM-containing formulations showed a hysteretic gelling behavior with transition temperatures between 10 and 55 degrees C. Gelation kinetics exhibited a lag time of 10 and 30 min at 25 and 37 degrees C, respectively. In vitro, fluorescein isothiocyanate-dextran was released from the gel in a sustained manner with less than 6% released after 20 days. The addition of ethanol to the LAM/oil mixture inhibited gelation and allowed subcutaneous injection of the solution at room temperature. After injection, ethanol diffusion led to the formation of a solid implant.


CONCLUSIONS
Low-molecular weight self-assembling organogelators may allow the preparation of novel in situ-forming hydrophobic implants.
Couffin-Hoarau
Anne-Claude
AC
Faculty of Pharmacy, University of Montreal, C.P. 6128 Succ. Centre-ville, Montreal, Quebec H3C 3J7, Canada.
Motulsky
Aude
A
Delmas
Pascal
P
Leroux
Jean-Christophe
JC
D000409:Alanine / Q000031:analogs & derivatives; D000818:Animals; D002626:Chemistry, Pharmaceutical; D005782:Gels / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D044366:Transition Temperature
D005782:Gels; D012997:Solvents; D000409:Alanine