In situ-forming pharmaceutical organogels based on the self-assembly of L-alanine derivatives

Purpose. 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 55degreesC. Gelation kinetics exhibited a lag time of 10 and 30 min at 25 and 37degreesC, 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.