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Molecular Product. Chemical product engineering asep muhamad samsudin. Chemical Products. Based on the characteristic size scale which is critical to their performance. Cussler and Moggridge.
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Molecular Product Chemical product engineering asepmuhamadsamsudin
Chemical Products Based on the characteristic size scale which is critical to their performance Cussler and Moggridge Cussler EL, Moggridge GD. Chemical product design. 2nd edition. Cambridge: Cambridge University Press; 2011.
Chemical Products R. Costa and G. D. Moggridge R. Costa, G. D. Moggridge, P. M. Saraiva. Chemical Product Engineering: An Emerging Paradigm Within Chemical Engineering. AIChE Journal, 52 (2006) :1979
Introduction • Molecular products are exemplified by pharmaceuticals. • These products, which sell for much more than the cost of their ingredients, are sold to perform a particular task, like curing a disease. • Molecular products depend on two keys: their discovery and their time to market. • Drug discovery is remarkably inefficient. In justifying the high prices for drugs, company executives sometimes assert that it takes 10,000 candidates to find one successful drug.
Introduction • Drug development begin by identifying the target disease, and if possible, what we wish to manipulate (e.g. a particular protein). • We then spend perhaps four years and over half a billion dollars seeking drugs which influence this disease. This huge. expensive, inefficient search is where so many compounds are identified, synthesized, and abandoned. • At the end of this saga, we begin animal testing, where our success rate is only about 10%. The animal testing will normally involve a sequence of mice. rats, and dogs. • At the end of this ordeal, we will have identified a possible target molecule. This is the point where engineering starts to become involved.
Introduction • This engineering involvement centers on the second key aspect of molecular products, the speed of their development or their time to market. • This is important because the first molecular product to be sold for a specific task normally garners two thirds of the sales in this area. • In this engineering-based development we will use the same design template of needs, ideas, selection, and manufacture to bring the chemical product to market. • We will decide what amounts and purity of the target molecule are needed. We will generate ideas to make and purify this molecule, and we will use generic equipment to manufacture batches of our product.
Characteristic of Molecular Products • Molecular products are high-value molecules, such as pharmaceuticals. • These molecules usually have molecular weights of 500 to 3000 daltons, though some antibodies can have molecular weights of several million. • These species are obtained in three different ways. • Antibiotics, like penicillin are examples of molecules produced by fermentation. • Prozac (fluoxetine), an antidepressant, is an example made by chemical synthesis. • Products are mixtures of pharmaceutically active species prepared by a specific process, often from a biological feedstock. e.g. Premarin
Characteristic of Molecular Products Prozac Penicillin Premarin
Characteristic of Molecular Products • Molecular products are typically made in small quantities, often less than ten tons per year. They sell for high prices, often over $100/kg. • One good example is Zoladex(goserelin acetate), a decapeptide used to treat both breast and prostate cancers. • Forty-six kilograms of the drug is made each year, selling for $800 million. Compounds like this are not synthesized in optimized. dedicated equipment, but are made periodically in generic equipment.
The Rule of Five • Suggested by C. A. Lipinski of Pfizer. • This rule, which does not apply to natural products, estimates the chance of clinical success for a drug to be administered orally. • It suggests that drugs must meet four criteria: • The drug must have five or fewer hydrogen-based donors.This is the sum of -OH and -NH groups. • The drug must have fewer than ten hydrogen-based acceptors. This is the sum of the molecule's nitrogen and oxygen atoms. • The drug's molecular weight must be under 500. This does not include species like HC1 or NaOH added to enhance solubility. • The logarithm of the drug's partition coefficient Kow between octanol and water must be less than five. In other words, its octanol solubility must be less than 100.000 times its water solubility. • The first and second rules describe the drug's chemistry; the third is a measure of size; and the fourth suggests that to reach human tissue, the drug must pass through water.
Clinical Trials • Phase I is a small study of around twenty healthy, paid volunteers. The study accesses the molecular product's toxicity and pharmacokinetics, usually inan outpatient clinic. • Phase II typically with 50 volunteers, some of whom have the target disease. Phase II includes studies of how much drug should be given and how well the drug works. Phase II is the step where most drugs fail, often because side effects are too serious. • Phase III, involving perhaps 1000 patients at several different locations, aims to collect statistically significant data for final submission, seeking approval for the drug from the FDA. These trials are tedious, averaging eight years for a new drug. They are a major reason why drugs are expensive,
Molecular Product Design • We will develop the process for such a product using our normal design sequence of "needs," "ideas," "selection," and "manufacture." • The "needs" step is easy: it is just the amount and purity of the target molecule to be made fast to meet the demands of the clinical trial. Needs may also include secondary constraints, such as discharge streams and available raw materials. • The "ideas" step is a several of possible processes drawn from laboratory experiments and published patents. Each process idea will include inventing a reaction-path sequence and separation processes. • The "selection" step is the hard one because we will need to simplify our process ideas quickly, and we will not have time to do the obvious but tedious experiments which would assure our success. • The "manufacturing" step will again be easy because its scale isn't so different to the bench process. Thus we need to work on the "ideas" and "selection" steps.
Synthesis of material flow for Molecular vs. Commodity Products • The sequence of decisions is the same, but the alternatives chosen are different.
Reaction-Path Synthesis • Once the target molecule is identified, the synthetic chemists on the team will start to think of possible routes for the synthesis. • Going backwards from the target molecule to simple precursors. called "the disconnection approach," is common. • This approach, outlined by Warren and Wyatt (2009). makes successive "disconnections" to reduce the target molecule to simple, available precursors. • Each disconnection involves imagining breaking the structure of the target molecule: this breakage is the reverse of a synthetic step. • Usually, several different disconnections are possible for any target molecule. Thus, many alternative synthetic routes can easily be deduced. • Sometimes. none of the potential routes will look viable. Alternativelv, it might be extracted from a natural product or made via fermentation.
Reaction-Path Synthesis Phenoglycodol Synthesis
Separation Synthesis General Rules • Concentrate the product before purification. • Remove the most plentiful products early. • Do the hardest separation last • Remove any hazardous materials early. • Avoid adding new species during the separation, If they must be added, remove them promptly. • Avoid extreme temperatures by using different solvents.
Separation Synthesis Fermentation Rules • Removal of insolubles. The fermentation broth or other natural feedstock is filtered. • Isolation. The product in the filtrate or the cake is isolated, that is concentrated. often by extraction. • Purification. The concentrate is partially purified, most often by chromatography. • Polishing. The purified product is purified again, most often by crystallization.
