Aggregate analysis/control

The specification development process is a data-driven activity that requires a validated analytical method. The levels of data needed include assay precision, replicate process results (process precision), and real-time stability profiles. A statistical analysis of these data is critical in setting a realistic specification. Most often, aggregation and fragmentation degradation mechanisms are common to protein and peptide therapeutics. Therefore, the SE-HPLC method provides a critical quality parameter that would need to be controlled by a specification limit. 

Bis(ethylacetoacetonate)-lanthanide(III) alkoxides, represented by structure (314), also initiate the well-controlled ROP of CL.895 Mn increases linearly with conversion (with Mw/Mn<1.10 throughout), and increasing [M]0/[I]o- Kinetic analysis implies a first order dependence on the lanthanide initiator, consistent with a non-aggregated active site. Block copolymers with moderately narrow polydispersities (1.25-1.45) have also been prepared using these initiators. NMR spectroscopy confirms well-controlled block sequences suggesting that these initiators are less susceptible to transesteriflcation than other lanthanide alkoxides. Initiation occurs exclusively at the alkoxide bond, and the tris(ethylacetoacetonate) analogs are inactive under the same conditions. 

The effects of size surface area, shape, purity method of synthesis, charge, surface coating, functionalized groups, and aggregation need to be carefully considered when assessing potential risks of CNT toxicity. Toxicology studies on CNTs should be accompanied by improved control in manufacturing and improved analysis before CNTs can be successfully used for pharmaceutical applications. 

Selected entries from Methods in Enzymology [vol, page(s)j Detection and quantification, 74, 608-616 effect of antigen/anti-body ratio, 74, 613, 614 applications, 74, 614-615 controls, 74, 612 data analysis, 74, 612-613 immunoglobulin G [conjugation to glucose oxidase, 74, 610 heat aggregation, 74, 609-610 heat denaturation, 74, 610 immobilization, 74, 610] precision, 74,... 

The mechanisms operating in the formation of textures seen in polycrystalline aggregates of the same species have been discussed in Sections 8.1-8.4. This may correspond to the analysis of a mechanism controlling the so-called selforganization or self-assemblage. Other mechanisms are possible for example, tiny spherical particles are assembled and a close-packed structure is formed due to surface tension. The formation of opal consisting of a close-packed structure of minute amorphous silica spheres maybe such a case. 

One can extend the above analysis to come up with the values of the packing parameter for which different shapes of aggregates are favored (Israelachvili 1991). These are summarized in Table 8.2. The results shown also serve as rules of thumb for what one can expect as one changes the chemical conditions of the solvent or the structure of the surfactant or for controlling the shape or aggregation number. For example,... 

Most of the reported in vivo data presented in the literature involves the infection of donor mice with a strain of P. berghe [61]. After a parasitemia of circa 30% is achieved in the donor mice, a blood sample is taken, diluted, and injected into experimental and control mice. The parasitemia load is regularly monitored for 3 to 7 days after infection by blood smear analysis as a function of drug dose. While in vivo efficacy assays reveal the true scope of a potential antimalarial s efficacy, the methods are very expensive. Consequently, additional assays have been developed to rapidly assess the effectiveness of lead heme aggregation inhibitors. 

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