Diffusion-controlled systems, control delivery

Matrix Diffusion. Historically, the most popular diffusion-controlled delivery system has been the matrix system, such as tablet and granules, where the drug is uniformly dissolved or dispersed, because of its low cost and ease of fabrication. However, the inherent drawback of the matrix system is its first-order release behavior with continuously diminishing release rate. This is a result of the increasing diffusional resistance and decreasing area at the penetrating diffusion front as matrix diffusion proceeds. 

Mathematically, the rate of drug delivery in diffusion-controlled delivery systems can be described by Pick s laws. Pick s first law of diffusion is expressed as ... 

Diffusion-Controlled Delivery of Proteins from Hydrogels and Other Hydrophilic Systems... 

Another critical consideration in protein delivery from hydrogel systems is the potential for protein denaturation in the device. For diffusion-controlled delivery systems, where water is the main transporting medium, the protein solution stability governs the type of device. Extended releasing times can be achieved with reservoir systems (Fig. 1) for highly stable proteins (Langer, 1990). Alternatively, dehydrated delivery systems... 

DIFFUSION-CONTROLLED DELIVERY SYSTEMS 2.1. Reservoir Systems... 

The polymer will play a passive role if it acts solely as a barrier which controls the rate of drug delivery by diffusion. Indeed, changes in the properties of the polymer are undesirable in this case since thereby the parameters governing the diffusion process will change. Purely diffusion controlled delivery systems generally belong to either one of two types, monolithic devices or reservoir devices. 

Because of their relative ease of production and cost compared with other methods of sustained or controlled delivery, dissolution and diffusion-controlled systems have classically been of primary importance in oral delivery of medication. Dissolution systems have been some of the oldest and most successful oral systems in early attempts to market sustaining products. 

Figure 4.1 Released amount Qt versus square-root-time -Jt plots. Illustration of loading less than or equal to saturation (dispersed, A < Cs) and greater than saturation (dissolved, A > Cs) in a matrix-type diffusion-controlled drug delivery system.

Transdermal delivery is a noninvasive intravenous infusion of drug to maintain efficacious drug levels in the body for predictable and extended duration of activity. Diffusion-controlled transdermal systems are designed to deliver the therapeutic agent at a controlled rate from the device to and through the skin into the systemic circulation. This route of administration avoids unwanted presystemic metabolism (first-pass effect) in the GI tract and the liver. Patient satisfaction has been realized through decreased... 

Figure 4.5 Transdermal diffusion-controlled drug delivery systems four design configurations and their basic elements.

Nondegradable subcutaneous implants as diffusion-controlled drug delivery systems, including Norplant, have been reviewed.89 99 Unlike biodegradable implants with long-term toxicological concern for metabolism of the polymer, nondegradable implants cannot avoid removal of the... 

Lee, P. Diffusion-controlled matrix systems, in Kydonieus, A. (ed.), Treatise on Controlled Drug Delivery Fundamentals, Optimization, Applications. New York Marcel Dekker, 1992, pp. 155—198. 

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