Reservoir devices/systems diffusion rate

Diffusion systems are characterized by the release rate of a drug being dependent on its diffusion through an inert membrane barrier. Usually this barrier is an insoluble polymer. In general, two types or subclasses of diffusional systems are recognized reservoir devices and matrix devices. These will be considered separately. 

Diffusion-controlled devices may be designed for continuous release and usually use either a matrix or reservoir construction. In matrix systems, the drug is dispersed randomly throughout a polymer, whereas reservoir devices surround the drug with an intact rate-controlling membrane. Regardless of the method of construction, the system must be safe and biocompatible for biological application. 

In an optimal release system, the rate of release is primarily determined by the design of the device itself, which is typically a polymer structure (Wise, 2000). A dmg can diffuse through the pores of the polymer system or by passing between the polymer chains. In a pure diffusion-controlled release system, there is no change occurring in the polymer itself. In matrix diffusion-controlled systems, the dmg can be either dissolved or dispersed throughout the polymer network, while reservoir diffusion-controlled... 

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. 

Buccal dosage forms can be of the reservoir or the matrix type. Formulations of the reservoir type are surrounded by a polymeric membrane, which controls the release rate. Reservoir systems present a constant release profile provided (1) that the polymeric membrane is rate limiting, and (2) that an excess amoimt of drug is present in the reservoir. Condition (1) may be achieved with a thicker membrane (i.e., rate controlling) and lower diffusivity in which case the rate of drug release is directly proportional to the polymer solubility and membrane diffusivity, and inversely proportional to membrane thickness. Condition (2) may be achieved, if the intrinsic thermodynamic activity of the drug is very low and the device has a thick hydrodynamic diffusion layer. In this case the release rate of the drug is directly proportional to solution solubility and solution diffusivity, and inversely proportional to the thickness of the hydrodynamic diffusion layer. 

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]. 

The microsealed delivery device is a variation of the matrix-type transdermal system in which the drug is dispersed in a reservoir phase which is then immobilized as discrete droplets in a cross-linked polymeric matrix. Release can be further controlled by inclusion of a polymeric microporous membrane. This system therefore combines the principles of both the liquid reservoir and matrix-type devices. Rate of release of a drug from a microsealed delivery system is dependent on the partition coefficient between the reservoir droplets and the polymeric matrix the diffusivity of the drug in the reservoir, the matrix and the controlling membrane and on the solubility of the drug in the various phases. There are, obviously, many ways to achieve the desired zero-order release rate, but only nitroglycerin has been commercially formulated into this type of delivery device (Karim 1983). 

Fig. 7. When such device is in contact with a solution or wet environment, the surrounding water molecules will diffuse across the membrane to the osmotic engine, which will increase the pressure inside the osmotic compartment. Then the piston will move forward to induce the gradual release of the dmg inside the drug reservoir through the outlet orifice. The water permeating flux is the most important parameter of such drug delivery system as it ultimately determines drug release rate.

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