Design and statistical optimization of glipizide loaded lipospheres using response surface methodology

Abstract

A 32 factorial design was employed to produce glipizide lipospheres by the emulsification phase separation technique using paraffin wax and stearic acid as retardants. The effect of critical formulation variables, namely levels of paraffin wax (X1) and proportion of stearic acid in the wax (X2) on geometric mean diameter (dg), percent encapsulation efficiency (% EE), release at the end of 12 h (rel12) and time taken for 50% of drug release (t50), were evaluated using the F-test. Mathematical models containing only the significant terms were generated for each response parameter using the multiple linear regression analysis (MLRA) and analysis of variance (ANOVA). Both formulation variables studied exerted a significant influence (p < 0.05) on the response parameters. Numerical optimization using the desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of dg, % EE, rel12 and t50 values for the optimized formulation were found to be 57.54 +/- 1.38 mum, 86.28 +/- 1.32%, 77.23 +/- 2.78% and 5.60 +/- 0.32 h, respectively, which were in close agreement with those predicted by the mathematical models. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion model. The optimized liposphere formulation developed was found to produce sustained anti-diabetic activity following oral administration in rats.

Sustained release microspheres of ropinirole hydrochloride: Effect of process parameters

“…The quadratic models generated from the regression analysis were used to construct 3-dimensional graphs, in which the response parameter Y was represented by a curved surface as a function of X. The effects of independent variables on the response parameters were visualized from the contour plots (18,19).…”

“…Models with major appliance and best describing drug release phenomena are the Higuchi model, zero-order model, Weibull model and Korsmeyer-Peppas model. The criteria for chooseing the ''best model'' to study drug dissolution/release phenomena are based on the use of the R value; the ''best'' model would be the one with the highest adjusted R (19).…”

Phospholipon 90H (P90H)–based PEGylated microscopic lipospheres delivery system for gentamicin: an antibiotic evaluation

“…The drug solubility and miscibility in melted lipid, chemical and physical structure of lipid materials, and their polymorphic state determine the loading capacity of drug in the lipid particles [4][5][6][7] . The amount of drug encapsulated can vary from 1 % to 5 % for hydrophilic compounds and up to 80 % for lipophilic compounds [8,9] .…”

Untitled

“…Its half-life is relatively short (25 h) which necessitates its administration in 2 or 3 doses of 2.5-10 mg/day. [6,7] Therefore, it is a potential candidate for the development of extended release formulations.…”

“…[5] It was the 6 th leading cause of death due to the many complications associated with this disease, such as pulmonary hypertension and ischemia. [3,6] Gliclazide is a second generation sulfonylurea that can acutely lower the blood glucose level in humans by stimulating the release of insulin from the pancreas and is typically prescribed to treat Type II diabetes. Its half-life is relatively short (25 h) which necessitates its administration in 2 or 3 doses of 2.5-10 mg/day.…”