Monolithic systems

As the agent evaporates or is removed from the surface of the monolithic device, more of the agent diffuses out from the interior to the surface in response to the decreased concentration gradient leading up to the surface. The release rate in physically dissolved, nonerodible plastomeric or elastomeric matrix is proportional to t until 60 % of the active agent is released. Thereafter, the release rate is related exponentially to time (Eq. 3.5). 

Release by erosion is a surface area-dependent phenomenon, and the general expression which describes the rate of release R, by an erosion mechanism is (Eq. 3.6)  

---

The most widely used exhaust control device consists of a ceramic monolith with a thin-waHed open honeycomb stmcture. The accessible surface of this monolith system is iacreased by applyiag a separate coatiag, a wash coat, of a high surface area material such as gamma-alumiaa with the catalyticaHy active species impregaated iato this washcoat. The catalyst aeeds to oxidize hydrocarboas, coavert CO to CO2, and reduce NO. The whole system forms a catalytic converter that, suitably encased, is placed between the engine and the muffler/silencer unit. 

A monolithic system is comprised of a polymer membrane with dmg dissolved or dispersed ia it. The dmg diffuses toward the region of lower activity causiag the release of the dmg. It is difficult to achieve constant release from a system like this because the activity of the dmg ia the polymer is constantly decreasiag as the dmg is gradually released. The cumulative amount of dmg released is proportional to the square root of time (88). Thus, the rate of dmg release constantly decreases with time. Again, the rate of dmg release is governed by the physical properties of the polymer, the physical properties of the dmg, the geometry of the device (89), and the total dmg loaded iato the device. 

The Minitran system, by 3M Health Care, is a monolithic transdermal system that deUvers nitroglycerin at a continuous rate of 0.03 mg/(cm h) (81). The dmg flux through the skin is higher than the previous two systems thus the Minitran system is a smaller size for equivalent dosing. For example, the 0.1 mg/h dose is achieved with a 3.3 cm system rather than the 5 cm systems of Transderm-Nitro or Nitro-dur. Because the skin is rate-controlling in a monolithic system and the Minitran flux is higher than the similar monolithic Nitro-dur system flux, it appears that 3M Health Care has included an additive to increase the skin flux to 0.03 mg/(cm h). Whereas this information is not apparent in Reference 81, patent information supports the hypothesis (96). 

Fig. 6. Catalyst inhibition mechanisms where ( ) are active catalyst sites the catalyst carrier and the catalytic support (a) masking of catalyst (b) poisoning of catalyst (c) thermal aging of catalyst and (d) attrition of ceramic oxide metal substrate monolith system, which causes the loss of active catalytic material resulting in less catalyst in the reactor unit and eventual loss in performance.

The concept of fibrous polymer formulations was extended to the delivery of aquatic herbicides (56). Several herbicides including Diquat, Fluridone, and Endothal were spun into biodegradable poly-caprolactone. Monolithic fibers and a modified monolithic system were produced with levels of herbicide from 5 to 60% by weight. Laboratory and field trials showed efficacious delivery of the active agent. Fibers provided both targeted localized delivery and controlled release of the herbicide to the aquatic weed. 

Micro Total Analysis Systems (pTAS) are chip-based micro-channel systems that serve for complete analytics. The word Total refers to the monolithic system character of the devices, integrating a multitude of miniature functional elements with minimal dead volumes. The main fields of application are related to biology, pharmacology, and analytical chemistry. Detailed applications of pTAS systems are given in Section 1.9.8. Recently, pTAS developments have strongly influenced the performance of organic syntheses by micro flow (see, e.g., [29]). By this, an overlap with the micro-reactor world was made, which probably will increase more and more. 

The granularity of the components and the corresponding unit of pluggability from monolithic systems, to client-server partitions, to the operating system and its services, to today s object-based component approaches. 

In a monolithic system, electronics and sensor part are integrated on a single chip. Separate circuitry and microsensor chips are characteristic for hybrid systems, as it is indicated by the dashed separation line in Fig. 2.1. The advantages and issues with hybrid and monolithic systems are extensively discussed in literature [14], so that only a few key points are mentioned here. The main disadvantage of monolithic systems is the limitation with respect to available materials and microtechnological process... 

A key issue in monolithic-system design is the simulation of the microhotplate coupled to the circuitry to ensure full chip functionahty. This requires an adequate description of the microhotplate and an implementation in a language that is applicable to circuitry simulations. 

Deleuze et al. used the same approach for the synthesis and functionalization of emulsion-derived polymeric foams [119]. Alternatively, a post-synthesis grafting method recently developed in our group offers access to high-capacity functionalized monolithic systems. Such high capacity monoliths are vital to various applications such as catalysis, extraction of environmental contaminants, extraction of biochemicals for either pharmaceutical or clinical purposes or, more generally, separation techniques [100]. With these systems, amounts of grafted monomers can exceed 1 mmol/g [94]. 

To model mass and energy transport in monolith systems, several approaches are discussed, leading from a representative channel spatially ID approach to 2D (1D+1D) modeling explicitly including washcoat diffusion. Correlations are given to describe heat and mass transfer between bulk gas phase and catalytic washcoat. For the detailed study of reaction-transport interactions in the porous catalytic layer, the spatially 3D model of the computer-reconstructed washcoat section can be employed. 

The presence of insoluble ingredients in the formulations helps to maintain the physical dimension of a hydrophobic matrix during drug release. As such, diffusion of the active form from the system is the release mechanism, and the corresponding release characteristic can be described by the Higuchi equation (Eq. 4.11). Very often, pores form within a hydrophobic matrix as a result of the release of the active ingredient. For a porous monolithic system, Eq. (4.11) can be further modified as18... 

Pillay, V., and Fassihi, R. A novel approach for constant rate delivery of highly soluble bioactives from a simple monolithic system. J. Contr. Rel. 67 67-78, (2000). 

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]. 

A salen-cobalt complex has been appended to the PASSflow monolith system to form catalyst 42 and used for the dynamic kinetic resolution of epibromohydrin, 43. Because 43 undergoes rapid racemization under the conditions used, all the starting materials can theoretically be converted to the desired diol 44 (Scheme 4.75). 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]. 

Water-soluble hydrophilic matrix systems may also be extruded, both to monolithic systems and to multiple-unit systems [12, 14-16], Polyethylene oxide (PEO) and chloropheniramine maleate have, for example, been extruded to a monolithic unit [113]. This manufacturing method proved more feasible for mixtures between low- and high-molecular-weight PEO, since systems containing only high-molecular-weight PEO proved too viscous and difficult to extrude. It was also... 

Achieving identical flow in each charmel can be difficult at low flow rates. A careful analysis of fhe hydrod)mamic sfabilify teaches that a monolith system is intrinsically unstable in cocurrent upflow. Conversely, cocurrent downflow is sfable when fhe flow velocity exceeds a critical value. A first approximation of fhe crifical flow velocify is fhe velocity that a liquid plug has when it falls under fhe influence of gravity inside the channel when it is open to the atmosphere at both ends. 

Figure 32 includes results illustrating the performance of lipase/car-bon monolith systems in an acylation reaction. For comparison, the free lipase and a commercial immobilized lipase (Novozyme) were also tested. As expected, in all cases the specific activity of immobilized lipase was foimd to be lower than that of the free enzyme. Such a difference is usually ascribed to conformational changes of the enzyme, steric effects, or denaturation. For the monolithic biocatalysts, the activity of the immobilized catalyst relative to that of the pure enzyme was found to be 30-35%, and for the Novozyme catalyst about 80% in the first rim. However, the Novozyme catalyst underwent significant deactivation, in contrast to the carbon monolith-supported catalysts. The deactivation of the Novozyme catalyst in consecutive runs is probably a consequence of the instability of the support matrix under reaction conditions (101,102). 

It is concluded that carbon/monolith systems, especially those incorporating CNFs, offer good potential value for catalysis involving liquid-phase reactants and for biocatalysis, as a consequence of the excellent accessibility of the active phase, which is present at the outside of the fibers, without any microporosity to offer a resistance interfering with the reaction. 

Awareness of the importance of air quality has triggered several home appliances of catalysts, whereby monoliths play a role. Table 6 gives several applications in the consumer sector. The limited lifetime of such applications overcomes a disadvantage of monolithic systems, in that they contain usually a relatively small amoimt of catalyst, and as a consequence, the buffer capacity against poisoning is less than that of conventional packed-bed reactors. In industrial operation, either robust catalysts or pure feeds are needed, but for home appliances, these criteria may be less of an issue. Similarly, for the use of N2O in hospitals, ambulances, etc., catalyst poisoning is less important. N2O decomposition can be achieved easily, and the use of a monolith structure is highly attractive for mobile applications. 

---