In situ-Forming Pharmaceutical Organogels Based on the Self-Assembly of L-Alanine Derivatives |
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Authors: | Couffin-Hoarau Anne-Claude Motulsky Aude Delmas Pascal Leroux Jean-Christophe |
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Institution: | Faculty of Pharmacy, University of Montreal, C.P. 6128 Succ. Centre-ville, Montreal, Quebec H3C 3J7, Canada. |
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Abstract: | 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 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. |
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Keywords: | in situ gelation organogel self-assembly sustained release |
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