Acta Pharm. 57
(2007) 269-285
10.2478/v10007-007-0022-8
Original research paper
Design and statistical optimization of glipizide loaded lipospheres
using response surface methodology
HAGALAVADI NANJAPPA SHIVAKUMAR, PRAGNESH BHARAT BHAI PATEL, BAPUSAHEB GANGADHAR DESAI, PURNIMA ASHOK AND SINNATHAMBI ARULMOZHI
shivakumarhn@yahoo.co.in
1Department of
Pharmaceutical Technology
2Department of
Pharmacology, K. L. E. S s College of Pharmacy, Bangalore-560010,
India
Accepted March 21, 2007
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 m, 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.
Keywords: lipospheres, glipizide, factorial
design, response surface methodology, optimization