Controlled release, rationale

The rationale for the development of such fibers is demonstrated by their appHcation in the medical field, notably hemoperfusion, where cartridges loaded with activated charcoal-filled hoUow fiber contact blood. Low molecular weight body wastes diffuse through the fiber walls and are absorbed in the fiber core. In such processes, the blood does not contact the active sorbent direcdy, but faces the nontoxic, blood compatible membrane (see Controlled RELEASE TECHNOLOGY, pharmaceutical). Other uses include waste industrial appHcations as general as chromates and phosphates and as specific as radioactive/nuclear materials. 

Hoffman, A., et al. 1998. Pharmacodynamic and pharmacokinetic rationales for the development of an oral controlled-release amoxicillin dosage form. J Control Release 54 29. 

A. Rubinstein, B. Tirosh, M. Baluom, T. Nassar, A. David, R. Radai, I. Gliko-Kabir, and M. Friedman, The rationale for peptide drug delivery to the colon and the potential of polymeric carriers as effective tools, J. Controlled Release 46 59-73 (1996). 

Sustained release (SR) preparations are not new but several new modifications are being introduced. They are also referred to as long acting or delayed release when compared to rapid or conventional release preparations. The term sometimes overlaps with controlled release, which implies more sophisticated control of release and not just confined to the time dimension. Controlled release implies consistency, but release of drug in SR preparations may not be consistent. The following are the rationale of developing SR ... 

Thies C, Dappert T. Statistical models for controlled release microcapsules Rationale and theory. Journal of Membrane Science. 1978 4 99-113. 

The rationale and use of modified-release formulations of antiepileptic drugs (carbamazepine, valproic acid, and tiagabine) have been reviewed (171). The authors concluded that modified-release formulations afford the advantages of better patient compliance, fewer adverse effects, and less fluctuation in plasma concentrations, making monitoring of drug concentrations easier. They concluded that these advantages should lead to better seizure control and improved quahty of life. 

A much more desirable erosion mechanism is surface erosion, where hydrolysis is confined to a narrow zone at the periphery of the device. Then, if the drug is weU-immobihzed in the matrix so that drug release due to diffusion is minimal, the release rate is completely controlled by polymer erosion, and an ability to control erosion rate would translate into an ability to control dmg delivery rate. For a polymer matrix that is very hydrophobic so that water penetration is limited to the surface (thus Hmiting bulk erosion), and at the same time, allowing polymer hydrolysis to proceed rapidly, it should be possible to achieve a drug release rate that is controlled by the rate of surface erosion. Two classes of biodegradable polymers successfully developed based on this rationale are the polyanhydrides [31] and poly (ortho esters) [32], the latter of which is the subject of this chapter. 

The rationale behind controlled or sustained release has always been the need for a therapeutic drug level that is sufficient without the overdose level that is generally found with injection or other forms of bolus medicant delivery. Oftentimes, there are undesirable side effects associated with bolus drug delivery and, in the case of certain drug therapies, a second drug must be administered to prevent side effects such as nausea. In theory, a properly designed controlled delivery device should overcome or minimize problems associated with pulsed drug delivery. 

As a general rule, all risk measures shall have passed test execution with satisfactory results. Exceptionally, a failed test case can be accepted if it has a very good rationale to explain that mitigation did not actually fail and safety is not compromised. Actual residual risk is then calculated and the release accepted or rejected based on the resulting residual risk and control outcome. 

Encapsulation is the process in which small particles are surrounded by a coating or shell layer. The main rationale for the encapsulation of substrates is to protect the substrate from the surrounding environment and to allow controlled or triggered release at a particular time. Key considerations are the degree of loading which is possible for a given particle, which can be... 

The latter process was termed biological mineralisation. The release of P and S in esters on the other hand is strongly controlled by the supply of, and need for the element which is released from soil organic matter by extracellular enzymes (biochemical mineralisation). These concepts, portrayed in Fig. 6, can accommodate the variability of C N S P ratios and the greater variability for P than for S in soil organic matter, and provide a rationale for understanding the stability of P in different soils. 

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