Pharmaceutical crystals

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. 

Togkalidou, T., Braatz, R.D., Johnson, B.K., Davidson, O. and Andrews, A., 2001. Experimental design and inferential modelling in pharmaceutical crystallization. American Institution of Chemical Engineers Journal, 47(1), 160-168. 

Price, S. L The computational predirtion of pharmaceutical crystal strurtures and polymorphism. Adv. Drug Deliv. Rev. 2004, 56, 301-319. 

Solubility modelling with activity coefficient methods is an under-utilized tool in the pharmaceutical sector. Within the last few years there have been several new developments that have increased the capabilities of these techniques. The NRTL-SAC model is a flexible new addition to the predictive armory and new software that facilitates local fitting of UNIFAC groups for Pharmaceutical molecules offers an interesting alternative. Quantum chemistry approaches like COSMO-RS [25] and COSMO-SAC [26] may allow realistic ab-initio calculations to be performed, although computational requirements are still restrictive in many corporate environments. Solubility modelling has an important role to play in the efficient development and fundamental understanding of pharmaceutical crystallization processes. The application of these methods to industrially relevant problems, and the development of new... 

G. Fevotte, In situ Raman spectroscopy for in-fine control of pharmaceutical crystallization and solids elaboration processes a review, Chem. Eng. Res. Des., 85, 906-920 (2007). 

G. Fevotte, New perspectives for the on-hne monitoring of pharmaceutical crystallization processes using in situ infrared spectroscopy, Int. J. Pharm., 241, 263-278 (2002). 

Three methods for chiral amine resolution are used in the manufacture of pharmaceuticals crystallization used most commonly enzymic resolution used occasionally chromatography used frequently during early phase and increasingly in commercial production. In each of these an isomer waste stream of at least 50% of the starting material is produced. 

Fluidized bed dryer lactose base granules, pharmaceutical crystals, weed killer, coal, sand, limestone, iron ore, polyvinyl chloride, asphalt, clay granules, granular desiccant, abrasive grit, and salt... 

Ammonium Bromide Lactose Base Granules Pharmaceutical Crystals Liver Residue Weed Killer... 

Findlay WP, Bugay DE. 1998. Utilization of fourier transform-raman spectroscopy for the study for pharmaceutical crystal forms. J. Pharm. Biomed. Anal. 16 921-930. 

True density of pharmaceutical crystals is typically between 1 and 2.5 g/mL... 

Fig. 1 Optical micrograph of Merck pharmaceutical crystals with poor filterability (200x).

Togkalidou, T. Tung, H.-H. Sun, Y. Andrews, A.T. Braatz, R.D. Parameter estimation and optimization of a loosely bound aggregating pharmaceutical crystallization using in situ infrared and laser backscattering measurements. Ind. Eng. Chem. Res. 2004, 43 (19), 6168-6181. 

Fujiwara, M. Nagy, Z.K. Chew, J.W. Braatz, R.D. First-principles and direct design approaches for the control of pharmaceutical crystallization. J. Proc. Control 2005, 15 (5), 493-504. 

R.D. Solution concentration prediction for pharmaceutical crystallization processes using robust chemometrics and... 

Patience, D.B. Dell Orco, P.C. Rawlings, J.B. Optimal operation of a seeded pharmaceutical crystallization with growth-dependent dispersion. Org. Proc. Res. Dev. 2004, (4), 609-615. 

Kawashima Y. Cui F, Takcuchi H. et al. Improvements in flowability and compressibility of pharmaceutical crystals for direct labletting by spherical crystallization with a 2-solvent system. Powder Technol 1994 78(2) 151-7. 

Vitez IM. Utilization of DSC for pharmaceutical crystal form quantitation. J Therm Anal Calorim 2004 78 33-45. 

Togkalidou, T, R.D. Braatz, B.K. Johnson, O.A. Davidson, and A.T Andrews (2001). Experimental design and inferential modeling in pharmaceutical crystallization. AIChE J. 47, 160-168. 

Togkalidou, T, H.H. Tung, Y. Sun, A. Andrews, and R.D. Braatz (2002). Solution concentration prediction for pharmaceutical crystallization processes... 

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