Crystallization of Organic Compounds: An Industrial by Hsien-Hsin Tung, Edward L. Paul, Michael Midler, James A.

Chemical Engineering

By Hsien-Hsin Tung, Edward L. Paul, Michael Midler, James A. McCauley

Packed with commercial examples emphasizing the sensible functions of crystallization methodologies.

Based at the authors' hands-on stories as strategy engineers at Merck, Crystallization of natural Compounds publications readers in the course of the useful facets of crystallization. It makes use of lots of case stories and examples of crystallization methods, starting from improvement via production scale-up. The e-book not just emphasizes concepts which have been confirmed profitable, it additionally is helping readers keep away from universal pitfalls which can render typical methods unsuccessful.

The objective of this article is twofold:
* construct a deeper realizing of the basic houses of crystallization in addition to the effect of those homes on crystallization strategy improvement.
* enhance readers' problem-solving talents through the use of real business examples with genuine approach constraints.

Crystallization of natural Compounds starts with special discussions of basic thermodynamic homes, nucleation and crystal progress kinetics, strategy dynamics, and scale-up issues. subsequent, it investigates modes of operation, together with cooling, evaporation, anti-solvent, and reactive crystallization. The authors finish with unique functions reminiscent of ultrasound in crystallization and computational fluid dynamics in crystallization. such a lot chapters function a number of examples that consultant readers step-by-step during the crystallization of lively pharmaceutical constituents (APIs).

With its specialize in business functions, this e-book is usually recommended for chemical engineers and chemists who're concerned with the improvement, scale-up, or operation of crystallization methods within the pharmaceutical and high-quality chemical industries.

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Example text

Therefore, it is highly desirable to grow thicker crystals. To grow “thick” crystals, experimentally, we should try to find the best solvent which favors the formation of such crystals. Meanwhile, solvates and hydrates may form in different solvent environments. Chemical forms, such as salt, free base, and free acid, can also be evaluated. Also, control of release of supersaturation and selection of crystallization conditions to enhance crystal growth over nucleation, which are addressed in the later chapters, would be very helpful.

Therefore, the formation of an amorphous solid is generally undesirable, although sometimes the compounds cannot generate a crystal form. Certain drugs, in particular those that are produced via freeze drying, are inherently amorphous solids. These amorphous drugs are made primarily to improve their dissolution rate in the human body, but at the expense of drug stability and subambient storage temperature (Leuner and Dressman 2000). The crystalline solid remains by far the most desirable form for drug formulation, although more attention has recently been given to amorphous solid dispersion (Lowinger et al.

2-19. Figure 2-19 Crystals of the anhydrous solid and the monohydrate crystals of ibuprofen lysinate. 34 Chapter 2 Properties A particular solvate is hydrate, in which water molecules form a solid adduct to the parent compound. Hydrate may not be stable below a certain water level, and may lose its water molecule and form anhydrous crystalline or amorphous solids. Above the crossover water level, hydrate is stable and always has lower solubility than the anhydrous solid (Khankari 1995). 2 are applicable for the measurement of nonsolvates and solvates.

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