Membrane-dispersed monolith

The buccal permeability of the non-steroidal antiinflammatory drug, diclofenac sodium, has been evaluated in a dog model. The dog was selected because of the similarity of its buccal mucosa to that of man. Analysis of the buccal data indicated that diclofenac sodium permeability followed an essentially zero-order kinetic process with a minimal lag phase. Permeability of the drug was estimated to be 3 mg/cm2.h but significant differences were observed between animals. The absorption rate with the transbuccal delivery device decreased with time whereas the corresponding rate with a saturated solution was constant. This difference was attributed to the time dependency of drug delivery from the device and was modeled on the basis of release from a membrane-dispersed monolith combined with constant buccal permeability. The predictions of the model showed excellent agreement with the experimental data. 

Drug release from the device was modelled on the basis of a membrane dispersed monolith (3) for which the net flux is given by... 

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. 

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]. 

One of the potential applications of these ABC triblock copolymers was explored by Hillmyer and coworkers in 2005 [118]. They have prepared nanoporous membranes of polystyrene with controlled pore wall functionality from the selective degradation of ordered ABC triblock copolymers. By using a combination of controlled ring-opening and free-radical polymerizations, a triblock copolymer polylactide-/j-poly(A,/V-dimethylacrylamide)-ib-polystyrene (PLA-h-PDMA-h-PS) has been prepared. Following the self-assembly in bulk, cylinders of PLA are dispersed into a matrix of PS and the central PDMA block localized at the PS-PLA interface. After a selective etching of the PLA cylinders, a nanoporous PS monolith is formed with pore walls coated with hydrophilic PDMA. 

Catalysts such as the platinum group metals can be used in dispersed or monolithic solid form. The catalyst can be deposited on the surface of a membrane (dense or porous) or, in the cases of catalyst particles, dispersed in the sub>surface layer or throughout the matrix of a porous membrane. 

Most research on controlled release polymeric systems has, however, centered on compositions in which a drug is either encapsulated in the center of a polymeric membrane (reservoir type) or dispersed throughout the polymer (monolithic type). The drug diffuses through the polymeric material to the surface where it is released to the body fluids. Such systems have been used to give... 

In most polymerizations the kind of dispersed system changes in the course of the process owing the fact that a gaseous or liquid monomer is transformed into a solid polymer. Examples are catalytic gas-phase polymerizations on solid catalyst beads (1) or polymerizations in liquid continuous phases of gaseous monomers. Heterophase polymerization can also be carried out in pores of inorganic solid materials such as Zeolites (2-5), or mesoporous MCM-41 and similar silicates (6,7), or inside interlayers of montmorillonite (8). Other special types of heterophase polymerizations in a solid continuous phase are used to modify the pores in solid polymer monoliths (9) or pores in polymeric membranes (10). 

Monoliths are continuous structures consisting of narrow parallel channels, typically with a diameter of 1-3 mm. A ceramic or metallic support is coated with a layer of material in which catalytically active components are dispersed (washcoat). The walls of the channels may be either permeable or impermeable. In the former case, the term membrane reactor (see above) is used. Figure 4.10.78 shows an example of a monolith. The shape of the monolith can be adapted to fit in the reaction chamber. 

The release of 5-fluorouracil from the [EMCF] copolymers follows a different mechanism than the release of 5-FU from a monolithic dispersion in poly(caprolactone). The copolymers consistently exhibit zero-order kinetics while the [FUPC] systems never show this pattern. In addition, much higher levels of the 5-FU can be incorporated into the polymeric system than into the monolithic dispersion system. In the present case, this was 45+% compared to less than 25%. For therapeutic use, the zero-order kinetics would offer the additional advantage of a completely controlled dose rate that could be maintained constant for long periods of time. The exact release rate can be controlled through the concentration of the drug monomer in the copolymer and the nature of the comonomer(s). This combination of properties can not be readily obtained in any other system without the use of complex membranes and the like. In short, the polymeric drug approach does offer many distinct advantages over the usual controlled release systems and should prove to be the more desirable system for use in medication. 

Due to the complexity of the mathematical treatment for cylindrical systems that include phenomena such as the presence of a diffusion boundary layer, a membrane that laminates the device surface and/or finite external medium, analytical solutions are difficult to obtain. Consequently, the study of drug release from cylindrical matrix systems using numerical methods is a common practice. Zhou and Wu analyzed in detail the release from cylindrical monolithic dispersion devices by using the finite element method [189]. 

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