Membrane reservoir system

For an ideal membrane, tL and tB emphasize the path length and the diffusion constant. Binding and heterogeneity of the membrane may complicate these simple relationships. In practice, as shown in Fig. 4.2, membrane reservoir systems have a period of constant release, i.e., steady -... 

Membrane-reservoir systems based on solution-diffusion mechanism have been utilized in different forms for the controlled delivery of therapeutic agents. These systems including membrane devices, microcapsules, liposomes, and hollow fibres have been applied to a number of areas ranging from birth control, transdermal delivery, to cancer therapy. Various polymeric materials including silicone rubber, ethylene vinylacetate copolymers, polyurethanes, and hydrogels have been employed in the fabrication of such membrane-reservoir systems (13). 

Unlike membrane-reservoir systems, the concentration distribution approach does not require a saturated reservoir and a rate-con-trolling membrane to achieve a constant rate of drug release. In addition, the onset of constant-rate release in the present approach can be almost instantaneous and the constant-rate releasing period can be relatively short. These are difficult to achieve in conventional membrane-reservoir systems. 

Cumulative Release from Membrane-Reservoir Systems... 

Membra.ne Diffusiona.1 Systems. Membrane diffusional systems are not as simple to formulate as matrix systems, but they offer much more precisely controlled and uniform dmg release. In membrane-controlled dmg deUvery, the dmg reservoir is intimately surrounded by a polymeric membrane that controls the dmg release rate. Dmg release is governed by the thermodynamic energy derived from the concentration gradient between the saturated dmg solution in the system s reservoir and the lower concentration in the receptor. The dmg moves toward the lower concentration at a nearly constant rate determined by the concentration gradient and diffusivity in the membrane (33). 

The hormone-releasing devices have a closer resemblance to standard methods of sustained release because they involve the release of a steroid compound by diffusion [198,199]. The Progestasert, a reservoir system, is shown in Fig. 16. Progesterone, the active ingredient, is dispersed in the inner reservoir, surrounded by an ethylene/vinyl acetate copolymer membrane. The release of progesterone from this system is maintained almost constant for 1 year. The effects of release are local, with none of the systematic side effects observed with orally administered contraceptives [200-207]. 

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. 

A typical reservoir system consists of a core (the reservoir) and a coating membrane (the diffusion barrier). The core contains the active ingredients and excipients, whereas the membrane is made primarily of rate-controlling polymer(s). The governing release mechanism is diffusion from the reservoir across the membrane to the bulk solution, and the one-dimensional release rate is described by Eqs. (4.4), (4.17), and (4.22).10,14 In addition,... 

Such design criteria have been successfully utilized in commercially available membrane-reservoir type of transdermal delivery systems for scopolamine, nitroglycerin, and more recently, estradiol (40,41). 

FIGURE 6.6 Schematic model for a membrane-reservoir sphere system. 

Steady-State Diffusion through a Membrane 6.2.2.1 Constant Activity Reservoir Systems... 

In microporous reservoir systems, drug molecules are released by diffusion through the micropores, which are usually filled with either water or oil (e.g. silicone, castor and olive oil). Solvent-loading of a porous membrane device is achieved simply by immersing the device in the solvent. When this technique presents some difficulty, the implantable device is placed inside a pressure vessel and pressure is then applied to facilitate the filling of the solvent into pores. The transport of drug molecules across such porous... 

Scopolamine was the first drug to be marketed as a transdermal delivery system (Transderm-Scop) to alleviate the discomfort of motion sickness. After oral administration, scopolamine has a short duration of action because of a high first-pass effect. In addition, several side-effects are associated with the peak plasma levels obtained. Transderm-Scop is a reservoir system that incorporates two types of release mechanims a rapid, short-term release of drag from the adhesive layer, superimposed on an essentially zero-order input profile metered by the microporous membrane separating the reservoir from the skin surface. The scopolamine patch is able to maintain plasma levels in the therapeutic window for extended periods of time, delivering 0.5 mg over 3 days with few of the side-effects associated with (for example) oral administration. 

In reservoir systems, a reservoir—whether solid drug, dilute solution, or highly concentrated drug solution with in polymer matrix—is surrouned by a film or membrane of a rate-controlling material [5]. The only structure effectively limiting the... 

The ER formulations can be a single-unit, monolithic system or multiple-unit systems containing many individual units with extended release. Multiple-unit systems consist of many small pellets and are normally produced by extrusion and spheronization or coating on inert spheres [2,10]. The composition and ER mechanism can vary for multiple-unit systems, and some examples are membrane-coated reservoir systems and polymer- or lipid-based matrix systems, where the matrices can be made of both soluble and insoluble carriers [11-16]. 

In ER reservoir systems, a membrane surrounds a reservoir of the drug, also called the core of the system. The membrane controls the drug release and the driving force is the difference in chemical potential over the membrane, which can be correlated with a concentration gradient over the membrane. The transport of the drug through the ER membranes can be divided into three different mechanisms [45-47] ... 

---