Reservoir systems controlled-release devices

This zero-order type of release is maintained if the reservoir contains a saturated solution and excess solid agent. This potential for zero-order release makes reservoir systems the most efficient of any type of controlled-release device. However, when the reservoir contains no excess solute the internal concentration falls with release of the agent, first-order release then results (Eq. 3.2). 

However, there are many ways in which we can both control drug release and get the zero-order behavior. Three common ways are a reservoir system, an altered device geometry, and an altered initial concentration profile. These three, shown schematically in Figure 19.1-3, are analyzed in the paragraphs that follow. 

Controlled release can be achieved by a wide range of techniques a simple but important example is illustrated in Eigure 45. In this device, pure dmg is contained in a reservoir surrounded by a membrane. With such a system, the release of dmg is constant as long as a constant concentration of dmg is maintained within the device. Such a constant concentration is maintained if the reservoir contains a saturated solution and sufficient excess of soHd dmg. 

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. 

The hormone-releasing devices in uterus have a closer resemblance to controlled release because they involve the release of a steroid compound by diffusion [82,83], Progesterone, the active ingredient, is dispersed in the inner reservoir, surrounded by ethlene/vinyl acetate copolymer membrane. The release of progesterone from this system is maintained almost constant for about a year [84-86],... 

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). 

Reservoir systems also have a backing and adhesive layer, but are contained by a rate-controlling membrane. The drug is contained within the reservoir as a suspension in a liquid or gel phase. The drug is released rapidly when the device is placed on the skin to give an initial burst effect. Thereafter, drug... 

Figure 9.2 Reservoir delivery systems based on rate-limiting polymer membranes. Rate-limiting polymer membranes can be used to produce several different types of drug delivery devices including (a) transdermal delivery systems, (b) planar con-trolled-release systems, and (c) cylindrical controlled-release systems.

According to the diffusion principle, controlled-release drug delivery systems can be designed as a reservoir system or a matrix system. Drugs released from both reservoir and matrix type devices follow the principle of diffusion, but they show two different release patterns as shown in Fig. 22.3. 

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... 

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... 

The most well known commercial reservoir controlled release systems deliver hormones for contraception from hydrophobic polymers. The Norplant subcutaneous device controls the release of levonorgestrel with silicone rubber, and the Progestasert intrauterine device (lUD) releases progesterone from reservoir devices of ethylene vinyl acetate. In the field of insecticides, reservoir dispensers called BioLure were developed to provide zero-order release ofinsect pheromones to disrupt mating (Smith et al, 1983). The dispenser consists of a slab configuration with a rate-controlling membrane, with constant release described by Eq. 1. 

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