Evaluation of various parameters on release of indomethacin from two-layered core osmotic pump

The novel drug delivery systems (NDDSs) have many advantages over traditional dosage forms such as longer duration, lower side effects, more uniformly blood concentrations and more patient compliance. Oral osmotic systems are NDDSs which can release their drug contents in long period of time (24h) with constant release rate. In this study we tried to formulate osmotic pump with two layered core and evaluate the effects of some parameters on the extent and kinetics of indomethacin release from it. Cellulose acetate was used as film former polymer in formulation of semipermeable membrane (SPM). Dip coating method was used for coating of the core tablets and a small orifice was drilled on one side of them by using standard microdrills. The drug release was tested by standard dissolution tester (paddle apparatus) and the drug concentration in the samples was measured by UV spectrophotometer. Various formulations were compared in terms of different parameter such as D10h (percent released within 10 hours), tL (lag time), Devzero (deviation of the drug release from zero order kinetics) and RSQzero. The results showed that SPM thickness has the significant effects on 10h and tL. tL was increased and D10h was decreased by increasing SPM thickness from 90 to 190μm regularly. The best drug release kinetic was observed in 130μm SPM thickness. Increasing orifice diameter from 350 to 80 μm improved D10h and tL but improvement in zero-order release kinetic of the drug was seen only to an optimum orifice diameter (700μm) also this parameter should be optimized in formulation. The results also showed a direct relationship between the amount of caster oil as lipophilic plasticizer and tL. D10h also decreased with increasing of caster oil in SPM formulation. Omitting of glycerine as hydrophilic plasticizer produced great enhancement in tL (46.7 in presence of 1.5% glycerin vs 207.8min for formulation without glycerine). with optimization of the main system parameters such as aperture diameter, SPM thickness, type and amounts of hydrophilic and lipophilic plasticizer, we can obtain suitable drug release (near zero order) from the osmotic system