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Download Controlled Drug Delivery: Fundamentals and Applications, by Joseph Robinson, Vincent H. L. Lee PDF

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By Joseph Robinson, Vincent H. L. Lee

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Performance of the controlled release systems may also be influenced by physiological constraints imposed by the particular route, such as first-pass metabolism, GI motility, blood supply, and sequestration of small foreign particles by the liver and spleen. Target sites: In order to minimize unwanted side effects, it is desirable to maximize the fraction of applied dose reaching the target organ or tissue. This can be partially achieved by local administration or by the use of carriers. However, the absorptive surfaces of most routes are impermeable to macromolecules or other targeted delivery systems, thereby necessitating either intravascular or intraarterial administration.

Riboflavin is absorbed by an active transport process, a process which is saturable [62] , and is preferentially absorbed in the upper part of the GI tract [63]. Consequently, unless this drug can be localized at the absorptive site one expects a gradation in absorption for this drug but this is not necessarily prohibitive. Indeed, riboflavin has been formulated in various sustained release multivitamin preparations. However, Morrison et al. [63] found that such preparations provided no demonstrable advantages over conventional preparations.

In summary, it would appear that drug properties can induce local and systemic side effects which can often be circumvented by placement in a suitable controlled release system. The specific controlled release mechanism employed depends on the drug property inducing side effects. F. Margin of Safety Among the indices used to describe the margin of safety of a drug [188-190], the therapeutic index as defined in Eq. (7) is the most widely used: 32 I Li et al. T h e r a p e u t i c i n d e x = Median toxic dose/median effective dose = TD50/ED5Q (7) However, t h i s ratio p r o v i d e s no information on (a) t h e n a t u r e of t h e d i s t r i b u t i o n of toxicity and e f f e c t i v e n e s s , (b) t h e size of doses p r o d u c i n g t h e r a p e u t i c and toxic effects, and (c) plasma or serum d r u g c o n c e n t r a t i o n s c o r r e s p o n d i n g to toxic and t h e r a p e u t i c l e v e l s .

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