Monolithic devices, controlled drug

Controlled Drug Release—Because the degradation products of Type III bioerosion are small, water soluble molecules, the principal application of polymers undergoing such degradation is for the systemic administration of therapeutic agents from subcutaneous, intramuscular or intraperitoneal implantation sites. Application of Type III bioerosion to controlled drug release was first described in 1970 (32) and has since then been extensively investigated. The various types of devices currently under development can be classified into (a) diffusional and (b) monolithic (7). 

Monolithic Devices—In these systems the drug is homogeneously dispersed within a bioerodible polymer matrix, and release of the drug can be controlled either by diffusion or by polymer erosion. If erosion of the matrix is very much slower than drug diffusion, then release kinetics follow the Higuchi model (37) and drug release rate decreases exponentially with time, following t dependence over a major portion of the release rate. 

A matrix system, often described as monolithic device, is designed to uniformly distribute the drug within a polymer as a solid block. Matrix devices are favored over other design for their simplicity, low manufacturing costs, and lack of accidental dose dumping, which may occur with reservoir systems when the rate controlling membrane ruptures. 

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. 

Diffusion-controlled membranes exist in two categories depot systems, in which the drug is totally encapsulated within a reservoir, and monolithic systems, where the drug is dispersed in a rate-controlling polymer matrix [25]. One commercially successful depot device is the Alza Ocusert for ocular delivery of pilocarpine in the treatment of glaucoma [25]. 

In developing such devices, two fundamentally different approaches are possible. In one, mechanism of drug release is by diffusion from a reservoir through a rate-limiting bioerodible pol3nner membrane, and in the other, drug release is controlled by matrix erosion. However, to achieve zero order drug delivery from monolithic erosional devices the erosion process must be confined to the surface of the solid device. ... 

The simplest configuration of a controlled release device is where a drug is either dissolved in high concentration or suspended as particles in a monolithic polymer such as a cylindrical polymer fiber. The release of the drug from it may occur via ... 

The second type of device is a monolithic system (Fig. 9, middle) incorporating a backing layer, a matrix layer, and an adhesive layer. The matrix layer consists of a polymer material in which the solid drug is dispersed the rate at which the drug is released from the device is controlled by this polymer matrix. With this type of system, the drug release rate falls off with time as the drug in the skin-contacting side of the matrix is depleted. 

Rod-shaped monolithic hydrogel devices with progesterine have been studied in the development of controlled release system for contraceptive application. It was found that progesterine release depends on the initial drug load, the degree of cross-linking, and the water content of the hydrogel. The first-order release was observed. 

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