title: Optimization of hydrogels for transdermal delivery of lisinopril by Box-Behnken statistical design.
abstract: The aim of this study was to investigate the combined influence of three independent variables on the permeation kinetics of lisinopril from hydrogels for transdermal delivery. A three-factor, three-level Box-Behnken design was used to optimize the independent variables, Carbopol 971 P (X(1)), menthol (X(2)), and propylene glycol (X(3)). Fifteen batches were prepared and evaluated for responses as dependent variables. The dependent variables selected were cumulative amount permeated across rat abdominal skin in 24 h (Q (24); Y(1)), flux (Y(2)), and lag time (Y(3)). Aloe juice has been first time investigated as vehicle for hydrogel preparation. The ex vivo permeation study was conducted using Franz diffusion cells. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the cumulative permeation of LSP in 24 h (Q(24)) was Y(1) = 1,443.3-602.59X(1) + 93.24X(2) + 91.75X(3) - 18.95X(1)X(2) - 140.93X(1)X(3) - 4.43X(2)X(3) - 152.63X(1)(2) - 150.03X(2)(2) - 213.9X(3)(2). The statistical validity of the polynomials was established, and optimized formulation factors were selected by feasibility and grid search. Validation of the optimization study with 15 confirmatory runs indicated high degree of prognostic ability of response surface methodology. The use of Box-Behnken design approach helped in identifying the critical formulation parameters in the transdermal delivery of lisinopril from hydrogels.
authors.affiliation: National Facilities in Engineering and Technology with Industrial Collaboration Centre, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506 009, Andhra Pradesh, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Gannu
authors.forename: Vamshi Vishnu
authors.initials: VV
authors.lastname: Yamsani
authors.forename: Shravan Kumar
authors.initials: SK
authors.lastname: Yamsani
authors.forename: Chinna Reddy
authors.initials: CR
authors.lastname: Palem
authors.forename: Madhusudan Rao
authors.initials: MR
authors.lastname: Yamsani
mesh_terms: D000279:Administration, Cutaneous; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D003627:Data Interpretation, Statistical; D020100:Hydrogels / Q000008:administration & dosage*; D017706:Lisinopril / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010539:Permeability; D051381:Rats; D012107:Research Design; D012867:Skin / Q000378:metabolism*; D014783:Viscosity
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D020100:Hydrogels; D017706:Lisinopril