PURPOSE: 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. MATERIALS AND 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.
PURPOSE: 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. MATERIALS AND 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.
Authors: S M Nuño-Donlucas; J C Sánchez-Díaz; M Rabelero; J Cortés-Ortega; C C Luhrs-Olmos; V V Fernández-Escamilla; E Mendizábal; J E Puig Journal: J Colloid Interface Sci Date: 2004-02-01 Impact factor: 8.128
Authors: B Mallikarjuna Rao; M K Srinivasu; K Praveen Kumar; Neelu Bhradwaj; R Ravi; Pradeep K Mohakhud; G Om Reddy; P Rajender Kumar Journal: J Pharm Biomed Anal Date: 2005-02-07 Impact factor: 3.935
Authors: Krista L Lanctôt; Nathan Herrmann; Kenneth K Yau; Lyla R Khan; Barbara A Liu; Maysoon M LouLou; Thomas R Einarson Journal: CMAJ Date: 2003-09-16 Impact factor: 8.262
Authors: Tânia M T Guimarães; Tânia Moniz; Cláudia Nunes; Maya Margaritova Zaharieva; Mila Kaleva; Krassimira Yoncheva; Hristo Najdenski; Sofia A Costa Lima; Salette Reis Journal: Pharmaceutics Date: 2022-03-30 Impact factor: 6.525
Authors: Tarek A Ahmed; Yasser A Alharby; Abdel-Rahim M El-Helw; Khaled M Hosny; Khalid M El-Say Journal: Drug Des Devel Ther Date: 2016-01-20 Impact factor: 4.162