Side-effects zero-order controlled release

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]. 

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... 

The state-of-the-art approach to controlled release opioid therapy is to provide formulations which exhibit zero order pharmacokinetics and have minimal peak to trough fluctuation in opioid levels with repeated dosing. This zero order release provides very slow opioid absorption, and a generally flat serum concentration curve over time. A flat serum concentration is generally considered to be advantageous because it would in effect mimic a steady-state level where efficacy is provided but side effects common to opioid analgesics are minimized. 

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