A rate-limiting membrane around a drug core, engineered for a near zero-order release profile.
In a reservoir system the drug is either molecularly dissolved or dispersed in a reservoir that is surrounded by a rate-limiting inert membrane. In a monolithic or matrix device this membrane is absent. Controlled delivery from a monolithic device is possible, but the presence of a membrane normally provides a better release profile. In principle, a zero-order release (constant release over time) can be approached with a reservoir system when the drug is dispersed in the core at a concentration far above the saturation solubility. The release of the drug occurs by diffusion of the drug molecules through the core and membrane of the reservoir system. Because of their suitable properties, polymers are often used in reservoir systems.
When the drug is dispersed in the core above saturation solubility, and the concentration outside the reservoir is almost zero (sink conditions), the concentration difference (ΔC) across the membrane can be regarded as almost constant. For a planar reservoir system this simplifies to a rate proportional to membrane area (A) and inversely proportional to membrane thickness (d), scaled by the interfacial partitioning coefficient K, related to drug solubility in the core (Cc) and in the membrane polymer (Cm).
To predict release rate for cylindrical and spherical geometries, Baker & Lonsdale describe equations based on cylinder length (h), and outer/inner membrane radius (ro, ri).
Coextrusion technology is commonly used to manufacture reservoir systems, multilayer flat films for transdermal delivery, or multilayer coaxial fibers for implants and vaginal rings. Two- and three-layer transdermal patch constructions allow one or more drugs to be delivered at the same time, though multilayer design must account for the physicochemical properties of every drug and excipient involved.
If the drug is dissolved, core concentration, and therefore release rate, gradually decreases over time, and because total dissolved drug is limited by saturation solubility, release time is typically short. If the drug is dispersed, release rate is controlled instead by membrane thickness, allowing much longer release durations since dispersed drug content can far exceed saturation concentration.
Storage & burst release: immediately after manufacturing, drug content in the membrane is zero, so release starts at zero and rises to steady state. If the reservoir is stored first, drug diffuses into the membrane until equilibrium, and the subsequent release curve shows an initial burst release, followed by steady state. For a planar system, the diffusion coefficient can be deduced from where the steady-state line intercepts the time axis: l²/3D (time-lag curve) and −l²/6D (burst-effect curve), where l is membrane thickness and D is the diffusion coefficient.
