Pharmaceuticals filtration

For some critical applications (such as polymer melt, beverage, or pharmaceutical filtration), it may be important to avoid cartridges that have a nap or fuzz on the fiber used, because these extremely fine fibers tend to break off and drift through the cartridge and go out with the finished product, thereby creating a isual acceptance problem, if not outi ight contamination. 

There are three (3) types of pharmaceutical filtrations depth, cake, and membrane. Cake and depth are coarse filtrations, and membrane is a fine, final filtration. Membrane filtration and cross-flow filtration are discussed in Ch. 7. 

The earliest commercially available filters were manufactured in two pore sizes 0.45 and 0.8 pm. The 0.45 pm-rated membranes were considered to be stefilizing-grade filters and were successfully used in the sterile filtration of pharmaceuticals and parenterals. The membrane filters were qualified using Serratia marcescens a standard bacterium, having dimensions of 0.6 x 1 pm. However, in the late 1960s it became apparent that the matrix of the 0.45 pm-rated filters could be penetrated by some pseudomonad-like organisms (1). For sterile filtration apphcations in the 1990s, 0.2 pm-rated membranes are the industry standard in the manufacture of sterile parenterals and pharmaceuticals. 

CiystaUization is the preferred method of forming many final prod-uc ts because veiy high purification is possible. High purity antibiotic ciystals can be produced from colored, rather impure solutions if the filter cake is uniform and amenable to good washingto remove the mother hquor. When a sterile pharmaceutical produc t is desired, ciystals are formed from liquid streams that have been sterihzed by filtration. 

Mathews and Rawlings (1998) successfully applied model-based control using solids hold-up and liquid density measurements to control the filtrability of a photochemical product. Togkalidou etal. (2001) report results of a factorial design approach to investigate relative effects of operating conditions on the filtration resistance of slurry produced in a semi-continuous batch crystallizer using various empirical chemometric methods. This method is proposed as an alternative approach to the development of first principle mathematical models of crystallization for application to non-ideal crystals shapes such as needles found in many pharmaceutical crystals. 

Pharmaceuticals for injection must be presented in a sterile form. Sterility may be achieved by filtration through 0.22 pm filters under aseptic conditions, or by steam, dry heat, radiation or gas sterilisation methods, which may be applied to packaged products. Irrespective of the method, the process must be validated and monitored to assure its effectiveness. As discussed in Chapter 2, this is an example of a process that cannot be assured by verification testing because of its destructive nature. 

NakadaN, Shinohara H, Murata A, Kiri K, Managaki S, Sato N, Takada H (2007) Removal of selected pharmaceuticals and personal care products (PPCPs) and endocrine-disrupting chemicals (EDCs) during sand filtration and ozonation at a municipal sewage treatment plant. Water Res 41 4373-4382... 

The British Pharmacopoeia (1993) recognizes five methods for the sterilization of pharmaceutical products. These are (i) dry heat (ii) heating in an autoclave (steam sterilization) (iii) filtration (iv) ethylene oxide gas and (v) gamma or electron radiation. In addition, other approaches involving steam and formaldehyde and ultraviolet (UV) light have evolved for use in certain situations. For each method, the possible permutations of exposure conditions are numerous, but experience and product stability... 

Principles of the methods employed to sterilize pharmaceutical products are described in Chapter 20. The British Pharmacopoeia (1993) recommends autoclaving and filtration as suitable methods applicable to aqueous liquids, and dry heat for non-aqueous and dry sohd preparatiorrs. The choice is determined largely by the ability of the formulation and container to withstand the physical stresses apphed by moist heat... 

Sterile pharmaceutical preparations must be tested for the presence of fungal and bacterial contamination before use (see Chapters 18 and 23). If the preparation contains an antibiotic, it must be removed or inactivated. Membrane filtration is the usual recommended method. However, this technique has certain disadvantages. Accidental contamination is a problem, as is the retention of the antibiotic on the filter and its subsequent liberation into the nutrient medium. 

Downstream Processing Microfiltration plays a significant role in downstream processing of fermentation products in the pharmaceutical and bioprocessing industry. Examples are clarification of fermentation broths, sterile filtration, cell recycle in continuous fermentation, harvesting mammahan cells, cell washing, mycelia recovery, lysate recovery, enzyme purification, vaccines, and so forth. 

Pharmaceutical Removal of suspended matter is a frequent application for MF. Processes may be either clarification, in which the main product is a clarified liquid, or solids recovery. Separating cells or their fragments from broth is the most common application. Clarification of the broth in preparation for product recovery is the usual objective, but the primary goal may be recovery of cells. Cross-flow microfiltration competes w l with centrifugation, conventional filtration by rotary vacuum filter or filter press and decantation. MF delivers a cleaner permeate, an uncontaminated, concentrated cell product... 

The use of palladium as a catalyst is common in the development and synthesis of active pharmaceutical ingredients (APIs). Palladium is an expensive metal and has no known biological function. Therefore, there is a need to recover spent palladium, which is driven both by cost and by government regulations requiring residual palladium in APIs to be <5 ppm (1). Thus, much research has been conducted with the aim of heterogenizing active palladium that can then be removed via simple filtration and hopefully reused without significant loss of activity. 

Before releasing a process column for chromatography, it is advisable to perform some test to measure efficiency, such as calculating height equivalent theoretical plates (HETP), both to forestall any problems in the column bed and to provide a benchmark by which to measure column reproducibility and predict degradation of the bed or material. Examples of compounds that are relatively innocuous for use in pharmaceutical applications are 1% NaCl (for gel filtration), concentrated buffer solutions (for ion exchange), and benzyl alcohol and parabens for reverse phase LC.10... 

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