Zero-order controlled release

Fig. 1. Zero-order (controlled) deflvery versus first-order (immediate-release) deflvery (repeated adrninistration). In 2ero-order deflvery, the dmg is released at a constant rate within the therapeutic range. In first-order deflvery, each administration of the dmg (represented by J.) causes semm-dmg concentrations...

Fig. 1 Drug level versus time profile showing differences between zero-order controlled release, slow first-order sustained release, and release from a conventional tablet or capsule.

Hsieh, D., Rhine, W., and Langer, R. Zero-order controlled release polymer matrices for micro and macro-molecules. J. Pharm. Sci. 72 17-22, 1983. 

A wide variety of drag delivery systems have been developed to achieve zero-order controlled release and are discussed further in the relevant chapters. 

Figure 1.10 Plasma concentration-time curve following oral administration of a zero-order controlled release dosage form...

The terminology describing dmg delivery and targeting is extensive and ever-growing. Systems are diversely referred to as controlled release , sustained release , zero-order , reservoir , monolithic , membrane-controlled , smart , stealth etc. Unfortunately, these terms are not always used consistently and, in some cases, may even be used inaccurately. For clarity and consistency, some common terms used in this book are defined as follows ... 

Potential for controlled release implants are available which deliver drags by zero-order controlled release kinetics. As discussed in Chapter 1 (Section 1.5.1), zero-order controlled release offers the advantages of ... 

For example, it is generally easier to fabricate a matrix-type implant than a reservoir system, so this may determine the selection of a matrix system. However, if drag release is the overriding concern, a reservoir system may be chosen in preference to a matrix system. This is because reservoir systems can provide zero-order controlled release, whereas drag release generally decreases with time if a matrix system is used. 

Figure 4.4 M t Zero-order controlled release profile of a reservoir-type nondegradable polymeric implant (porous or compact membrane)...

Infeld, M.H., Malick, A.W., Phuapradit, W, Shah, N.H. Pharmaceutical compositions with constant erosion volume for zero-order controlled release, US 5393765 A, 1995, 21pp. 

Gellan gumdamarind seed polysaccharide Metformin HCl Mucoadhesive beads The in-vitro drug release from the beads showed controlled-release (zero-order) pattern over a period of 10 h. [151]... 

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. 

The investigators studied various blends of the three polymers in order to control the rate of chain scission and thus influence the induction period and onset of drug release. None of the blends provided the desired 1-week zero-order kinetics. However, blends of different microsphere types did show promise in vitro (88). 

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... 

Controlled release, although resulting in a zero-order delivery system, may also incorporate methods to promote localization of the drug at an active site. In some cases, a controlled-release system will not be sustaining, but will be concerned strictly with localization of the drug. Site-specific systems and targeted-delivery systems are the descriptive terms used to denote this type of delivery control. 

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... 

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