As expected, rheological measurements clearly indicate that the flow behavior is dependent on the polyacrylate concentration. With increasing concentrations of this gelling agent, an increase in the dynamic viscosity can be observed (Fig. ). The results from the drug release experiments (Fig. ) are in good agreement with these observations. From all gel formulations, acetaminophen was released with an almost constant rate that was close to zero-order kinetics (Table ). The release rate was strongly dependent on the concentration of the gelling agent and consequently on the gel viscosity. In the case of low viscous gels obtained for polyacrylate concentrations of 0.05% and 0.1%, drug delivery was completed within 30 and 60 min, respectively. In contrast, gels with higher polyacrylate concentrations showed incomplete drug release within the test duration of 8 h, i.e., 80% of the dose was released from the gel containing 0.15% of gelling agent and only about 20% of the dose from the gel containing 0.30% of polyacrylate. In this work, the capillary was prefilled with the gel prior the dissolution and so no lag time in the delivery profiles was observed. However, if the capillary will not be prefilled, it is possible to achieve lag times depending on the gel viscosity. The lack of dose dumping is related to system robustness and usage of uniformly drug-loaded gels which viscosity remained constant during the delivery time. In the present setup, the system is activated by the temperature increase above BP of isopentane. However, by sealing the capillary with polymers of desired properties, it become likely that besides the temperature the water contact or pH could trigger the delivery process.
Fig. 3 Mean drug release profiles of the novel drug delivery system loaded with gels containing different concentrations of polyacrylate (USP apparatus 2, 50 rpm, 1,000 ml USP phosphate buffer pH 6.8, 37°C, means of n (more ...)
Slopes of the Dissolution Profiles and the Corresponding Regression Coefficients
The results indicate that by using liquefied gas-based drug delivery systems, it is possible to achieve zero-order release kinetics over highly variable time spans for liquid or semisolid drug formulations. Further changes of the drug delivery characteristic can be achieved by the modification of capillary parameters (length, radius) as well as by use of propellants with different vapor pressures.