title: 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.
authors: Department of Pharmaceutical, K.L.E.S's College of Pharmacy, Bangalore-560010, India. shivakumarhn@yahoo.co.in
authors: Hagalavadi Nanjappa
authors: HN
authors: Shivakumar
authors: Pragnesh Bharat
authors: PB
authors: Patel
authors: Bapusaheb Gangadhar
authors: BG
authors: Desai
authors: Purnima
authors: P
authors: Ashok
authors: Sinnathambi
authors: S
authors: Arulmozhi
mesh_terms: D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003460:Crystallization; D003692:Delayed-Action Preparations; D015195:Drug Design; D005913:Glipizide / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D015233:Models, Statistical; D010316:Particle Size; D016062:Porosity; D051381:Rats; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D008081:Liposomes; D005913:Glipizide