In situ-forming oleogel implant for rivastigmine delivery.
OBJECTIVE
To provide a simplified dosing schedule and potentially reduce side effects associated to peak plasma concentrations, an in situ-forming oleogel implant was studied for the sustained-release of rivastigmine.


METHODS
The gel was prepared by dissolving 5-10% (w/w) N-stearoyl L: -alanine methyl ester (SAM) organogelator in safflower oil containing either dissolved rivastigmine or its dispersed hydrogen tartrate salt. Rheological analysis, differential scanning calorimetry, and infrared spectroscopy were carried out to assess the impact of drug incorporation on the oleogel; this was followed by in vitro and in vivo release studies.


RESULTS
A weakening of intermolecular interactions was suggested by gel-sol transition temperature drops of 10-15 degrees C upon incorporation of dissolved drug. Meanwhile, the dispersed drug salt induced minimal or no changes in transition temperature. Gels containing dispersed rivastigmine had the lowest burst in vitro (<15% in 24 h). In vivo, the 10% SAM formulation containing dispersed rivastigmine provided prolonged drug release within the therapeutic range for 11 days, with peak plasma levels well below the toxic threshold and up to five times lower than for the control formulation.


CONCLUSIONS
This study established SAM gels to be a promising option for sustained-release formulations in the treatment of Alzheimer's Disease.
Vintiloiu
Anda
A
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, PO Box 6128, Downtown Station, Montreal, QC, Canada H3C 3J7.
Lafleur
Michel
M
Bastiat
Guillaume
G
Leroux
Jean-Christophe
JC
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D004343:Drug Implants; D007279:Injections, Subcutaneous; D008297:Male; D008855:Microscopy, Electron, Scanning; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D009930:Organic Chemicals; D048448:Phenylcarbamates / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D020318:Rats, Long-Evans; D012212:Rheology; D000068836:Rivastigmine; D012450:Safflower Oil / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D044366:Transition Temperature
D002800:Cholinesterase Inhibitors; D004343:Drug Implants; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D048448:Phenylcarbamates; C016021:oleogels; D012450:Safflower Oil; D000068836:Rivastigmine
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