Zero-order release

This equation describes the steady-state, or zero-order, release of the dmg. When the dmg completely dissolves, its concentration within the system begins to dilute, and the release rate foUows a parabohc decline with time (102). Acutrim (ALZA Corp.), dehvering phenylpropanolamine hydrochloride [154-41 -6] for appetite suppression, is an example of an elementary osmotic pump. 

Bezemer JM, Radersma R, Grijpma DW, Dijkstra PJ, Feijen J, and van Blitterswijk CA. Zero-order release of lysozyme from poly(ethylene glycol)/poly(butylenes terephthalate) matrices. Control Rel, 2000, 64, 179-192. 

Recently, Tsakala et al. (90) formulated pyrimethamine systems based on several lactide/glycolide polymers. These studies were conducted with both microspheres (solvent evaporation process) and implants (melt extrusion process). In vitro studies indicated that pyrimethamine-loaded implants exhibited apparent zero-order release kinetics in aqueous buffer whereas the microspheres showed an initial high burst and considerably more rapid drug release. In vivo studies in berghi infected mice confirmed that the microspheres did not have adequate duration of release for practical application. However, the implants offer promise for future clinical work as more than 3 months protection was observed in animals. 

In the treatment of chronic diseases, a long term zero order release dosage form is highly desirable as it reduces fluctuations of drug levels, reduces toxicity and increases patient compliance. Problems in the treatment of both hypertension, a lifetime disorder, and opiate addiction are associated with compliance. The goal of this research is to develop a subcutaneously injectable system which can release drug at constant rates over a long period of time. 

The rate and type of release can be analyzed by the expression Mt/Moo=ktn (76). In the case of pure Fickian diffusion n = 0.5, whereas n > 0.5 indicates anomalous transport, i.e., in addition to diffusion another process (or processes) also occurs. If n = 1 (zero order release), transport is controlled by polymer relaxation ("Case II transport") (76). The ln(Mt/Mco) versus In t plots, shown in Figure 4, give n = 0.47 and 0.67 for samples A-9.5-49 and A-4-56, respectively. Evidently theophylline release is controlled by Fickian diffusion in the former network whereas the release is... 

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... 

Since the left side of Eq. (7) represents the release rat of the system, a true controlled-release system with a zero-order release rate can be possible only if all of the variables on the right side of Eq. (7) remain constant. A constant effective area of diffusion, diffusional path length, concentration difference, and diffusion coefficient are required to obtain a release rate that is constant. These systems often fail to deliver at a constant rate, since it is especially difficult to maintain all these... 

Disadvantages Cannot obtain zero-order release... 

Drug surrounded by semipermeable membrane and release governed by osmotic pressure Zero-order release obtainable Reformulation not required for different drugs... 

NR Vyavahare, MG Kulkarni, RA Mashelkar. Zero order release from glassy hydrogels. n. Matrix effects. J Membrane Sci 54 205-220, 1990. 

CG Varelas, DG Dixon, CA Steiner. Zero-order release from biphasic polymer hydrogels. J Controlled Release 34 185-192, 1995. 

Zero order release over a period of time... 

A, the fitted Weibull parameters listed in Table 2 and the remaining model parameters as listed in Figure 4 (panel a) or the assumed zero order release rates of 4%, 5%, and 6.7% per hour (panel b). 

The predicted concentration-time profiles for all three formulations are shown in Figure 5 (panel a). These simulations use the fitted in vitro profiles for input to the model. For comparison, the simulations assuming zero order release are shown in panel b. Although the zero order simulations may be useful for initial specification of target profiles, they offer little of value for selecting specific formulations for the in vivo study or for study design (e.g., selection of sampling times),... 

I Brand Name(s) Entaprin, Halfprin, St. Joseph, YSPAspirin, Zero-Order Release, ZOR-prin... 

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