Microparticulation

Another example is the purification of a P-lactam antibiotic, where process-scale reversed-phase separations began to be used around 1983 when suitable, high pressure process-scale equipment became available. A reversed-phase microparticulate (55—105 p.m particle size) C g siUca column, with a mobile phase of aqueous methanol having 0.1 Af ammonium phosphate at pH 5.3, was able to fractionate out impurities not readily removed by hquid—hquid extraction (37). Optimization of the separation resulted in recovery of product at 93% purity and 95% yield. This type of separation differs markedly from protein purification in feed concentration ( i 50 200 g/L for cefonicid vs 1 to 10 g/L for protein), molecular weight of impurities (<5000 compared to 10,000—100,000 for proteins), and throughputs ( i l-2 mg/(g stationary phasemin) compared to 0.01—0.1 mg/(gmin) for proteins). 

The most innovative photohalogenation technology developed in the latter twentieth century is that for purposes of photochlorination of poly(vinyl chloride) (PVC). More highly chlorinated products of improved thermal stabiUty, fire resistance, and rigidity are obtained. In production, the stepwise chlorination may be effected in Hquid chlorine which serves both as solvent for the polymer and reagent (46). A soHd-state process has also been devised in which a bed of microparticulate PVC is fluidized with CI2 gas and simultaneously irradiated (47). In both cases the reaction proceeds, counterintuitively, to introduce Cl exclusively at unchlorinated carbon atoms on the polymer backbone. 

Microamorphous silica can be divided into microparticulate silica, ie, microscopic sheets and fibers, and highly hydrated silica (1). The... 

Fat Replacers. The reduction of fat in substitute dairy products results in an increase in water and a stress on the food system both in respect to body and texture, and to flavor. There is no universal fat replacer, but microparticulated proteins having particle sizes <10 fim and/or starch derivatives, and gums have been used as fat replacers. 

Whey proteins that have been heat precipitated under very high shear have a particle size between 1 and 3 micrometers, and give the impression of fat in some products. These microparticulated whey proteins are being used as fat replacers in frozen desserts and processed cheese substitutes. 

Microparticulate Systems - Although dual combination treatment systems comprising microparticles and flocculants have been used in the paper industry since the 1980s, it is only recently that there has been a general trend for paper mills to switch from conventional single component systems to dual systems. 

Finally, the useful life of an analytical column is increased by introducing a guard column. This is a short column which is placed between the injector and the HPLC column to protect the latter from damage or loss of efficiency caused by particulate matter or strongly adsorbed substances in samples or solvents. It may also be used to saturate the eluting solvent with soluble stationary phase [see Section 8.2(2)]. Guard columns may be packed with microparticulate stationary phases or with porous-layer beads the latter are cheaper and easier to pack than the microparticulates, but have lower capacities and therefore require changing more frequently. 

Andrianov AK, Payne LG (1996) In Cohen S, Bernstein H (eds) Microparticulate systems for the delivery of propetins and vaccines. Dekker, New York, chap 4, p 127... 

Emulsion formed from vitamins and/or carotenoids, gelatins (pH 2 to 4.6), saccharose, starch, and water emulsion drops are added to powder of starch to form microparticulates by heat treatment at 120 to 170 C to give powder... 

Cox, G. B., Loscombe, C. R., Slucutt, M. J., Sugden, K., and Upfield, J. A., The preparation, properties and some applications of bonded ion-exchange packings based on microparticulate silica gel for high-performance liquid chromatography, J. Chromatogr., 117, 269, 1976. 

Alpert, A. J. and Regnier, F. E., Preparation of a porous microparticulate anion-exchange chromatography support for proteins, /. Chromatogr., 185, 375,1979. 

In NPLC, which refers to the use of adsorption, i.e. liquid-solid chromatography (LSC), the surface of microparticulate silica (or other adsorbent) constitutes the most commonly used polar stationary phase normal bonded-phase chromatography (N-BPC) is typified by nitrile- or amino-bonded stationary phases. Silica columns with a broad range of properties are commercially available (with standard particle sizes of 3, 5 and 10 im, and pore sizes of about 6-15nm). A typical HPLC column is packed with a stationary phase of a pore size of 10 nm and contains a surface area of between 100 and 150m2 mL-1 of mobile phase volume. 

MJ Alonso. Nanoparticulate drug carrier technology. In S Cohen, H Bernstein, eds. Microparticulate Systems for the Delivery of Proteins and Vaccines. New York Marcel Dekker, 1996, pp 203-242. 

Negatively charged particles are more rapidly cleared from the blood than are neutral and positive ones [75], The clearance rate of particles by the reticuloendothelial system is inversely related to the load of the particles that is, the rate of clearance of a larger dose of microparticulate is slower than for a smaller dose [76],... 

Microparticulate Systems for the Delivery of Proteins and Vaccines, edited by Smadar Cohen and Howard Bernstein... 

Analytical hplc these days is nearly always done with microparticulate column packings, which are small porous particles, usually spherical or irregular silica, with nominal diameters of 3,5 or 10 fxm. They combine the best features of the other two types, having high efficiency as well as a large surface area. In bulk, the appearance of a microparticulate silica resembles that of a fine talcum powder. With microparticulates, dry packing methods result in column beds that are unstable under pressure, so they are packed into columns using a slurry of the material in a suitable solvent and under considerable pressure. 

Fig. 3.1b lists some of the properties of two commercially available microparticulate packings. The first is a 5 /im unmodified silica, the second a 3 fim silica, chemically modified with octadecylsilane (ODS, C-18). 

You twill find as you get further involved with hplc that there is a bewildering Zariety of microparticulate packings available in the trade literature. The textbook by Hamilton and Sewell (second Edition, Chapter 4) has an extensive list, as do most other textbooks. To keep things in perspective, remember that almost all the work in... 

Microparticulate silicas have been used in a number of different ways in hplc (these were mentioned in the introduction) ... 

Microparticulate silica can be used in a number of modes for hplc of these, reverse phase chromatography using bonded phases is the most widely used. In normal and reverse phase chromatography the retention times and selectivities of solutes can be altered by adjustment of the nature and composition of the mobile phase. 

A number of specialised stationary phases have been developed for the separation of chiral compounds. They are known as chiral stationary phases (CSPs) and consist of chiral molecules, usually bonded to microparticulate silica. The mechanism by which such CSPs discriminate between enantiomers (their chiral recognition, or enantioselectivity) is a matter of some debate, but it is known that a number of competing interactions can be involved. Columns packed with CSPs have recently become available commercially. They are some three to five times more expensive than conventional hplc columns, and some types can be used only with a restricted range of mobile phases. Some examples of CSPs are given below ... 

The surface of microparticulate silica can be modified by the attachment of different groups to produce bonded phases. Reverse phase chromatography using bonded phases is generally faster and easier than other modes, and consequently has achieved very wide popularity. 

Ionic solutes can be separated by ion-exchange chromatography using microparticulate resins or bonded ion-exchangers based on microparticulate silica. Such separations are often achieved more easily by ion-suppression or ion-pairing techniques, which use bonded phase columns in the reverse phase mode. 

A microparticulate hplc column is a very efficient filter, and if the mobile phase contains any particulate matter, or acquires it from the pump and/or the injection valve due to wear, it will collect at the top of the column. If this happens, the pressure drop across the column for a given flow will gradually increase, and the column may eventually become completely blocked. To prevent this happening, the mobile phase should always be filtered before use, preferably through a 0.5 p,m porosity filter, and guard and scavenger columns should be used as a matter of routine (see Section 5.3.2). 

---