Scalable processes

The goals of the project were to confirm the molecular weight of hementin, determine the N-terminal amino acid sequence, and provide sufficient purified protein for biochemical studies of the fibrinolytic activity. These goals were all attained. Many of the issues that become important in devising a scalable process were identified, particularly... 

Function Mechanical Optical Qrgano-leptic Vapour barrier Scalability Processability... 

Insofar as the scale-up of pharmaceutical liquids (especially disperse systems) and semisolids is concerned, virtually no guidelines or models for scale-up have generally been available that have stood the test of time. Uhl and Von Essen [54], referring to the variety of rules of thumb, calculation methods, and extrapolation procedures in the literature, state, Unfortunately, the prodigious literature and attributions to the subject [of scale-up] seemed to have served more to confound. Some allusions are specious, most rules are extremely limited in application, examples give too little data and limited analysis. Not surprisingly, then, the trial-and-error method is the one most often employed by formulators. As a result, serendipity and practical experience continue to play large roles in the successful pursuit of the scalable process. 

It is very important to stress that the large parameter space in homogeneous catalysis is not represented by the number of metal-ligand combinations alone. To discover a cost-effective scalable process for many transformations, many other parameters have to be considered and optimized. For example, consider the choice of the following important reaction parameters for a given transformation four different ligand/metal ratios, four different pressures, three different substrate/metal ratios, three different solvents, and two different temperatures. The inclusion of these parameters into a HT screen will result in almost 300 experiments for each metal-ligand combination ... 

In this way, we obtained FddA via F-ara-A (42) in a fairly good overall yield from 6-chloropurine riboside. However, to establish a scalable process, each reaction step must be improved and further investigations are needed to optimize conditions for fluorination and deoxygenation on an industrial scale. 

The demand for increasing control of physical attributes for final bulk pharmaceuticals has necessitated a shift in emphasis from control of nucleation to control of growth. This trend is also finding application for control of purity and improved downstream handling for both intermediates and final bulk products. The obvious critical factors then become seeding and control of supersaturation. Quantification of these factors for each growth process is essential for development of a scalable process. Much of the discussion to follow focuses on the growth process and methods to minimize nucleation. 

These many interacting rate processes may aU be at play in a reactive crystaUization. Successful development of a consistent and scalable process requires evaluation of the potential for each to be significant so that methods of control can be developed. 

The hydrolytic kinetic resolution (HKR) of racemic terminal epoxides catalyzed by chiral (salen)-Co(III) complexes provides efficient access to epoxides and 1,2-diols, valuable chiral building blocks, in highly enantioenriched forms. While the original procedure has proved scalable for many substrates, several issues needed to be overcome for the process to be industrially practical for one of the most useful epoxides, epichlorohydrin. Combined with kinetic modelling of the HKR of epichlorohydrin, novel solutions were developed which resulted in linearly scalable processes that successfully addressed issues of catalyst activation, analysis and reactivity, control of exothermicity, product isolation, racemization, and side-product formation. 

An Efficient and Scalable Process for the Preparation of a Potent MC4 Receptor Agonist... 

After evaluating each of the proposed routes, we came to the conclusion that the one-step Fischer indole-type reaction b was the most promising as a scalable process despite a low yield. Ready availability of the starting raw materials (p-tolylhydrazine and 4,4-diethoxy-butylamine) at low cost compensates for the low productivity of that transformation. 

Develop simple, reproducible, and potentially scalable processes for producing SWNTs. 

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