Microcapsules reservoir

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). 

Controlled release formulations are a recent innovation in which the pesticide is incorporated into a carrier, generally a polymeric material (Scher, 1999). The rate of release of the pesticide is determined by the properties of the polymer itself as well as environmental factors. There are mainly two types of CR formulations reservoir devices and monolithic devices. As shown in Figure 2.1, in the reservoir device, the toxicant is enclosed in capsules of thin polymeric material to become microcapsules (1-100 pm in diameter), e.g., Penncap-M microcapsules (methyl parathion). In the monolithic device, the toxicant is uniformly... 

Mathiowitz [35 0] realizes reservoir-type delivery systems recurring to a photochemical control. Microcapsules, built up by interfacial polymerization of polyamide, also contain azobisisobutyronitrile, a substance that emanates nitrogen due to a photochemical action. Accordingly, after exposition to light, microcapsules internal pressure increases (as a result of nitrogen release) until membrane rupture and consequent contents release. 

Yeo, Y. Basaran, O.A. Park, K. A new process for making reservoir-type microcapsules using ink-jet technology and interfacial phase separation. J. Controlled Release 2003, 93 (2), 161-173. 

The internal structure of microspheres may vary as a function of the microencapsulation process employed. " Reservoir microcapsules have a core of... 

It may be necessary to consider the effect of a boundary layer on the release rate. A boundary layer of appreciable drug concentration on the surface of the device would hinder drug release by diffusion. The effect of the layer is more marked with drugs of low solubility and with microparticles having irregular surfaces. From this simple example, it can be seen that various factors affect the release rate from reservoir microcapsules. 

Nevertheless, monolithic microspheres can be made to release drug at an approximately constant rate. " The core loading of these microspheres may be increased to create structures similar to those of reservoir microcapsules. An optimum combination of particle sizes (a size distribution), may be prepared to achieve a constant rate of drug release. Preparing microspheres with an erodible polymer in such a way that maximum erosion occurs in conjunction with minimum diffusion may establish a constant release rate. Although the principles described here appear simple, they are difficult to utilize because of their dependence on a number of factors, each of which can complicate the process. 

The release rates that are achievable from a single microcapsule are generally 0 order, 1/2 order, or 1st order. 0 order occurs when the core is a pure material and releases through the wall of a reservoir microcapsule as a pure material. The 1/2-order release generally occurs with matrix particles. Ist-order release occurs when the core material is actually a solution. As the solute material releases from the capsule the concentration of solute material in the solvent decreases and a Ist-order release is achieved. Please note that these types of release rates occur from a given single microcapsule. A mixture of microcapsules will include a distribution of capsules varying in size and wall thickness. The effect, therefore, is to produce a release rate different from O , 1/2 , or 1 because of the ensemble of microcapsules. It is therefore very desirable to examine carefully on... 

FIGURE 11.8 Schematic morphologies of the two types of microcapsules, (a) Core-shell microcapsule or reservoir and (b) matrix type microcapsule. (From Lembo, D. and Cavalli, R., Antivir. Chem. Chemother., 21, 53,2010.)... 

The active constituent/encapsulating material ratio is usually high in reservoir systems (between 0.70 and 0.95), whereas for matrix systems, this ratio is generally lower than 1.5 (more commonly between 0.2 and 0.35). The delivery devices defined in 1 are often referred to as microcapsules and those described in 2 are called microspheres. 

FIGURE 32.2 Schematic diagram of microcapsules morphology (a) reservoir system (simple wall) (b) matrix system (c) simple wall (liquid core) (d) multicore (e) simple wall (solid and irregular core) and (f) matrix (solid core dispersed into the polymeric matrix). 

FIGURE 32.3 Release from reservoir device (microcapsule) fractured by mechanical forces. 

Microsphere reservoirs for controlled release applications in medicine, cosmetics and fragrances are obtained evaporating solvent fi om an oil-in-water emulsion. The microcapsules have diameters of fi om 3 to 300 im. Many polymers are suitable for use in this invention which is based on the knowledge that the inclusion of plasticizer renders porous and spongy structure as opposed to the hollow core and relatively solid surface which results when no plasticizers are used. 

Reservoir delivery systems have been developed in a variety of styles, ranging from microcapsules to hollow fibers to liposomes. Hayashi et al. (1994) produced delivery systems by encapsulating proteins and hormones inpoly-L-lactide microspheres by a solvent evaporation method. The release mechanism for hormones entrapped in liposomes was studied by Ho et al (1986). Progesterone and hydrocortisone skin permeation was enhanced by the presence ofthe liposomes no penetration ofthe liposomes was observed. Examples ofthe most common hydrogels employed in reservoir systems are crystalline-rubbery PEG, PAAm, celluloses, PAA, and PHEMA. 

Mechanisms of Release. In Figure 3, Line A represents release from a reservoir system with a large core relative to the wall mass. This could be a microcapsule releasing by steady-state diffiision through a uniform nonerodible wall. Transport through the polymer membrane (or matrix) occurs by a dissolution-diffusion process, where the active ingredient first dissolves in the polymer and then diffuses across the polymer to the external surface where the concentration is lower. The diflfiision is in accordance with Fick s first law ... 

Physical Methods. Physical methods are divided into two general approaches. The pesticide is entrapped within a physical structure either at a molecular or micro-domain level or the pesticide in the form of a reservoir is enclosed within a polymeric envelope (2). In the first approach, the pesticide is mixed with the polymer (or other material with high energy density) to form a monohthic structure or matrix. Release is normally through diffusion through the matrix or dissolution and erosion of the matrix. In the second approach, structures are based upon a reservoir of the pesticide enclosed by the polymer, from nano-scale up to centimeter-sized devices. The shapes of these devices are varied and include spherical, such as microcapsules, and laminar or layered structures with the reservoir bounded by permeable membranes. These membranes provide a permeable barrier which controls the release rate. Other mechanisms of release include capsule rupture and erosion of the membrane. 

Matrix Particles. Small particles based on a matrix can range in size from powders (microparticles) to granules (fine to macrogranules) to pellets (43). Microspheres can be considered as the matrix equivalent to microcapsules. Most controlled release granules are matrix-based, although some have a solid core or reservoir of pesticide (with a coating). 

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