The aim of the current work was the design and evaluation of
etodolac controlled porosity osmotic pump (CPOP)
tablets exhibiting zero-order release kinetics. Variables influencing the design of (1) core
tablets viz., (a) osmogent type (
sodium chloride,
potassium chloride,
mannitol, and
fructose) and (b)
drug/osmogent ratio (1:0.25, 1:0.50, and 1:0.75), and (2) CPOP
tablets viz., (a) coating
solution composition, (b)
weight gain percentage (1-5%, w/w), and (c) pore former concentration (5%, 10%, and 20%, v/v), were investigated. Statistical analysis and kinetic modeling of drug release data were estimated.
Fructose-containing core
tablets showed significantly (P < 0.05) more retarded drug release rates. An inverse correlation was observed between
drug/
fructose ratio and drug release rate. Coating of the optimum core
tablets (F4) with a mixture of
cellulose acetate solution (3%, w/v),
diethyl phthalate, and
polyethylene glycol 400 (85:10:5, v/v, respectively) till a 4% w/w
weight gain enabled zero-order sustained
drug delivery over 24 h. Scanning electron microscopy micrographs of coating membrane confirmed pore formation upon contact with dissolution medium. When compared to the commercial immediate-release Napilac® capsules, the optimum CPOP
tablets (F4-34) provided enhanced bioavailability and extended duration of effective
etodolac plasma concentration with minimum expected potential for side effects in healthy volunteers.