Zero-order release phase

Equation 9 describes the zero-order release phase from the frustum. 

The release kinetics are characterized by an initial lag-phase, a zero release phase and a depletion phase. During the lag-phase water intrudes into the polymer matrix and activates the latent catalyst. During the zero-order release phase, an equilibrium between water intrusion and polymer erosion is established and an eroding front, (V2), that penetrates the device is established. Because thin disks were used, device geometry remains essentially constant and zero order release uncomplicated by a decrease in total surface area is observed. The depletion phase characterizes a decrease in device and depletion of the incorporated acidic excipient. 

As can be seen in Figure 4a, incorporation of dDAVP in the liquid crystalline phase significantly prolongs the apparent half-life of the peptide. No decline in plasma dDAVP-LI was found during the observation period of five hours, and the level of dDAVP-LI in plasma thus seems to correlate with an apparent zero-order release process of dDAVP. No difference in plasma dDAVP-LI could be found between sc and im administration. 

The inclusion of Somatostatin into a cubic phase markedly prolonged the apparent half-life. As can be seen in Figure 4b, the plasma level of Somatostatin-like immunoreactivity (SRIF-LI) after sc administration of cubic preparations of SRIF was nearly constant during the observation time of six hours, and no decline in the plasma level could be seen. During this period, the level of SRIF-LI in plasma thus seems to correlate with a zero-order release process of SRIF (cf. dDAVP). In Figure 4b is also shown the plasma SRIF-LI after sc administration of the peptide solubilized in cubic phases with varying ratios of MO/LE. It can be seen that increasing the amount of LE... 

A device consisting of an array of frustum-shaped cells that contain a drug dispersed in a permeable matrix is shown to obey zero-order release kinetics following an initial burst phase. Geometric shapes of dissolving solids or diffusion systems and the constraints of impermeable barriers influence mass transport and can be exploited as in the constant release wedge- or hemispheric-shaped devices. 

The microsealed delivery device is a variation of the matrix-type transdermal system in which the drug is dispersed in a reservoir phase which is then immobilized as discrete droplets in a cross-linked polymeric matrix. Release can be further controlled by inclusion of a polymeric microporous membrane. This system therefore combines the principles of both the liquid reservoir and matrix-type devices. Rate of release of a drug from a microsealed delivery system is dependent on the partition coefficient between the reservoir droplets and the polymeric matrix the diffusivity of the drug in the reservoir, the matrix and the controlling membrane and on the solubility of the drug in the various phases. There are, obviously, many ways to achieve the desired zero-order release rate, but only nitroglycerin has been commercially formulated into this type of delivery device (Karim 1983). 

Iwatsubo and Pantaloni 121) demonstrated that the rate-limiting step in oxidation of glutamate is release of the reduced coenzyme, confirming an earlier conclusion based on steady-state measurements 315). Subsequently, Fisher et al. 322) and DiFranco and Iwatsubo 323) indicated that reduction of NADP can be resolved into a three-part process, a rapid, first-order burst followed by a slower, zero-order, second phase, then an approach to equilibrium. Fisher et al. 322) demonstrated that replacement of the a-hydrogen of the substrate by deuterium results in a significant slowing of the burst phase but has little effect on subsequent steps, thus indicating that hydride ion abstraction is involved in the burst. 

McGee, J. P., Davis, S. S., and O Hagan, D. T., 1995, Zero order release of protein from poly(D,L-lactide-co-glycolide) microparticles prepared using a modified phase separation technique, J. Controlled Release 34 17-86. 

With the advance of pharmaceutical science, it has been recognized that constant release is not the only way to maximize drug effectiveness and minimize side effects and that the assumptions used for constant release rate sometimes fail due to physiological conditions. From this perspective, zero-order dmg release is not acceptable in all cases and externally modulated or self-regulating dmg delivery systems have been developed as novel approaches to deliver dmgs as required. To realize such dmg delivery systems, it is important to constmct a system where the dmg itself senses environmental stimuli and responds appropriately to control the dmg release. For this purpose, the phase transition polymers have been intensively exploited as a candidate material during last decade [21]. 

The release profile of ketoprofen from the 2/3 CAP coated core (KET-R CAP tablet) was of zero order (y=0.037x-1.263, r=0.99) and the drug release rate was clearly lower than the original core, as is shown in Fig. 5. However, the technique of preparation of KET-R CAP tablets was somewhat complex, requiring considerable accuracy in the partial coating phase, and not easily applicable on an industrial scale. 

The buccal permeability of the non-steroidal antiinflammatory drug, diclofenac sodium, has been evaluated in a dog model. The dog was selected because of the similarity of its buccal mucosa to that of man. Analysis of the buccal data indicated that diclofenac sodium permeability followed an essentially zero-order kinetic process with a minimal lag phase. Permeability of the drug was estimated to be 3 mg/cm2.h but significant differences were observed between animals. The absorption rate with the transbuccal delivery device decreased with time whereas the corresponding rate with a saturated solution was constant. This difference was attributed to the time dependency of drug delivery from the device and was modeled on the basis of release from a membrane-dispersed monolith combined with constant buccal permeability. The predictions of the model showed excellent agreement with the experimental data. 

Core/shell particles exhibit a number of features which make them very useful for controlled (sustained or triggered) release purposes. The release kinetics may be zero-order (constant rate) or first order (exponentially decreasing with time. In sustained release, the release kinetics is primarily determined by the structure of the core. Solid cores (i.e. of the active molecule itself) will give rise to zero-order kinetics during sustained release through a shell. Clearly, there must, in this case, be a reverse flow of liquid from the continuous phase back... 

In zero-order reactions the amount of product formed varies with time so that the amount of product formed after 20 minutes will be twice that formed after 10 minutes. Reactions that follow zero-order kinetics are quite rare, but they do occur in solid-phase reactions such as release of drug from a pharmaceutical suspension. 

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