Solid dispersions surface-active carriers

Another surface-active carrier useful for preparing solid dispersion formulations is tocopheryl polyethylene glycol 1000 succinate (TPGS)o0iR-tocopheryl PEG 1000 succinate (Eastman Chemical,... 

HIV Protease Inhibitor. The bioavailability of ritonavir (Norvir, Abbott), an HIV protease inhibitor, was enhanced by formulation as a solid dispersion in a mixture of surface active carrier, such as Gelucire 50/13, polysorbate 80, and polyoxyl-35 castor oil. 

If it is not possible to improve the bioavailability of a substance as desired by the addition of a solubilizing agent, this is frequently because the surface area of the crystals of active ingredient exposed to the solvent is too small. It is therefore necessary to increase the surface area, to accelerate dissolution. The first solid dispersions with antibiotics in povidone were described in the literature in about i960 [49,60]. In solid solutions and dispersions the active substance is embedded in a hydrophilic carrier to improve its bioavailability. The difference between a solid solution and a solid dispersion can be defined in terms of the state of the active substance. In a solid solution, it is present in an amorphous molecular form, while in a solid dispersion it is in the form of crystals that must be as fine as possible. 

The use of a support allowing the HPA to be dispersed over a large surface may result in an increase of its catalytic activity. The performance of supported HPA catalysts depends on the carrier, the HPA loading, conditions of pretreatment, among other variables. Acidic or neutral solids such as active carbon, Si02 and ZrOz are suitable as supports [1]. But HPA often leaks out of catalyst supports even in vapor-phase reactions. It is important, for practical purposes, to develop supported catalysts which can be applied to several reactions with no leakage of HPA. 

Solid-Phase Components. Dispersed sohds are vital ingredients in commercial antifoam formulations. Much of the cmrent theory on antifoaming mechanism ascribes the active defoaming action to this dispersed solid phase with the liquid phase primarily a carrier fluid, active only in the sense that it must be surface-active in order to carry the solid particles into the foam films and cause destabilization. For example, PDMS, despite its considerable effectiveness in nonaqueous systems, shows little foam-inhibiting activity in aqueous surfactant solutions. It is only when compounded with hydrophobic silica [7631-86-9] to give the so-called silicone antifoam compounds that highly effective aqueous defoamers result. The three main solid-phase component classes are hydrocarbons, silicones, and fluorocarbons. 

Most industrial catalysts are heterogeneous catalysts consisting of solid active components dispersed on the internal surface of an inorganic porous support. The active phases may consist of metals or oxides, and the support (also denoted the carrier) is typically composed of small oxidic structures with a surface area ranging from a few to several hundred m2/g. Catalysts for fixed bed reactors are typically produced as shaped pellets of mm to cm size or as monoliths with mm large gas channels. A catalyst may be useful for its activity referring to the rate at which it causes the reaction to approach chemical equilibrium, and for its selectivity which is a measure of the extent to which it accelerates the reaction to form the desired product when multiple products are possible [1],... 

Catalysts were some of the first nanostructured materials applied in industry, and many of the most important catalysts used today are nanomaterials. These are usually dispersed on the surfaces of supports (carriers), which are often nearly inert platforms for the catalytically active structures. These structures include metal complexes as well as clusters, particles, or layers of metal, metal oxide, or metal sulfide. The solid supports usually incorporate nanopores and a large number of catalytic nanoparticles per unit volume on a high-area internal surface (typically hundreds of square meters per cubic centimeter). A benefit of the high dispersion of a catalyst is that it is used effectively, because a large part of it is at a surface and accessible to reactants. There are other potential benefits of high dispersion as well— nanostructured catalysts have properties different from those of the bulk material, possibly including unique catalytic activities and selectivities. 

When the mass of carrier material is large relative to that of the enzyme, the physical and chemical properties of the carrier (Table 6-5) will, in large part, determine properties of the resultant immobilized enzyme. Often, the carrier will impart mechanical strength to the enzyme, allowing repetitive recovery by simple filtration of the solid particles and reuse of the enzyme. The degree of porosity and pore volume will determine the resistance to diffusion and molecular size selectivity of the biocatalyst. When used in non-aqueous media, dispersion of the enzyme over a large surface area can greatly increase its activity. Table 6-3 summarizes many of the key properties and considerations for enzyme carrier materials. 

A second and somewhat simpler approach that can be applied to obtain supported ionic liquid catalyst systems involves the treatment of a solid, porous carrier material by a substantial amount of a catalytically active ionic liquid, allowing the reaction to take place in the dispersed phase. In these systems the ionic liquid phase can itself act as the catalytically active component or it may contain other dissolved compounds or reagents, for example, transition metal complexes, which function as the catalytically active species (i.e. generating SILP catalysts). Importantly, the ionic liquid catalyst phase in these SILP catalyst systems are confined to the carrier surface only by weak van der Waals interactions and capillary forces interacting in the pores of the support. In special cases electrostatic attachment of the ionic liquid phase may also be applied. Usually, the catalysts are prepared by traditional impregnation techniques, where a volatile solvent is used initially to reduce viscosity for the impregnation process and is finally removed by evaporation leaving the ionic catalyst solution dispersed on the support. 

Because the accelerating effect of the solid catalyst comes from the surface atoms, it is desirable to have the largest surface possible, meaning a high degree of dispersion of the substance in question. In most cases, very small particles of catalytically active material such as platinum or rhodium are applied for stability to highly porous carrier materials with specific surfaces of several hundred square meters per gram. Aluminum oxide, silicon dioxide, activated carbon, as well as zeolites (crystalline aluminosilicates with numerous submicroscopic pores and canals) are all suitable for this purpose. Examples of such supported catalysts are... 

We will here focus on nanoparticles as a typical example of nano-carriers. Nanoparticles can be seen as sub-micron colloidal objects with a predominantly elastic mechanical behaviour (solid-like bodies), which can be loaded with therapeutically active compounds on their surface, in their bulk or both. Drug-loaded nanoparticles have been administered as nano-carriers in water-based dispersions through virtually all parenteral routes, i.e., intravenous, subcutaneous, intramuscular and also intraperitoneal, but they have also been used to prepare macroscopic materials in situ (Fig. 12.1). 

Solid catalysts are mostly used in the form of small grains or pellets, varying in size from approximately 10 fim to 10 mm. They often consist of two components, a continuous solid phase, usually with a high porosity (the carrier), and a finely dispersed solid phase, which adheres to At internal surface (the pore walls) of the carrier. The dispersed solid phase is the more active cat ytic material, and is considered as the catalyst proper. However, in many processes the carrier surface is also catalytically active. 

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