title: Formulation optimization of galantamine hydrobromide loaded gel drug reservoirs in transdermal patch for Alzheimer's disease.
abstract: Galantamine hydrobromide (GH) is an effective drug for Alzheimer's disease. It is currently delivered via the oral route, and this might cause nausea, vomiting, and gastrointestinal disturbance. In the present work, GH was formulated in a gel-type drug reservoir and then optimized by using response surface methodology (RSM) based on central composite design. This optimization study involved three independent variables (carbopol amount, triethanolamine amount, and GH amount) and two dependent variables (cumulative drug release amount at 8 hours and the permeation flux of drug). Two models using expert design software were fitted into a quadratic polynomial model. The optimized gel was formulated with 0.89% w/w carbopol, 1.16% w/w triethanolamine, and 4.19% w/w GH. Optimization analysis revealed that the proposed formulation has the predicted cumulative drug release amount at 8 hours of 17.80 mg·cm(-2) and the predicted permeation flux of 2.27 mg·cm(-2)/h. These predicted values have good agreement to actual cumulative drug release amount at 8 hours (16.93±0.08 mg·cm(-2)) and actual permeation flux (2.32±0.02 mg·cm(-2)/h). This optimized reservoir formulation was then fabricated in the transdermal patch system. This patch system has moderate pH, high drug content, and controlled drug-release pattern. Thus, this patch system has the potential to be used as the drug carrier for the treatment of Alzheimer's disease.
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Fong Yen
authors.initials: FY
authors.lastname: Woo
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia ; Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Mahiran
authors.initials: M
authors.lastname: Basri
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Hamid Reza Fard
authors.initials: HR
authors.lastname: Masoumi
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Mansor B
authors.initials: MB
authors.lastname: Ahmad
authors.affiliation: Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Maznah
authors.initials: M
authors.lastname: Ismail
mesh_terms: D000279:Administration, Cutaneous; D000544:Alzheimer Disease / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D004983:Ethanolamines / Q000737:chemistry; D005702:Galantamine / Q000737:chemistry / Q000494:pharmacology*; D005782:Gels / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D011145:Polyvinyls / Q000737:chemistry; D015203:Reproducibility of Results; D012984:Software; D057968:Transdermal Patch
chemical_list: D003692:Delayed-Action Preparations; D004983:Ethanolamines; D005782:Gels; D011145:Polyvinyls; D005702:Galantamine; C009546:triethanolamine
keywords: Franz diffusion cell; analysis of variance; central composite design; response surface methodology