Pharmaceutical solids high temperature

Methods for the determination of solubility have been thoroughly reviewed [21,22], Solubility is normally highly dependent on temperature, and so the temperature must be recorded for each solubility measurement. Plots of solubility against temperature, as exemplified by Fig. 4 [23,24], are commonly used for characterizing pharmaceutical solids and have been extensively discussed [1,24]. Frequently (especially over a relatively narrow temperature range), a linear relationship may be given either by a van t Hoff plot according to [23]... 

A classical liquid-solid sample preparation technique is Soxhlet extraction. The apparatus consists of a pot of extracting solvent which is refluxed to provide fresh hot solvent to drip through the solid sample. Solubility is maximized by using the clean hot solvent for dissolution. The sample is contained in a porous thimble held between the solvent flask and the reflux condenser. The Soxhlet technique is not often used in routine pharmaceutical sample preparations for two reasons the high temperature can cause degradation which is unacceptable for stability-indicating assays, and the technique is difficult to perform on multiple samples because of time and space requirements. 

Solid-eatalyzed reactions can occur in either the liquid or gas phase. Gas-phase reactions are not very common in the production of fine chemieals, beeause eom-plex molecules with limited volatility and thermal stability are usually involved, which makes operation at the high temperatures required for their vaporization impossible. Gas-liquid reactions with a solid catalyst probably encompass the largest number of applications in fine-chemical and pharmaceutical processes [1]. Two other classes of solid-eatalyzed reaction taking place in the liquid phase are liquid-solid reactions and liquid-liquid-solid reactions, but these are much less eommon. We shall, therefore, foeus on gas-liquid-solid reaetions, in which the solid is a heterogeneous catalyst. 

If sfarfing materials and products are volatile and stable enough, the reaction can be performed in a gas phase wifh a solid catalyst. But, unfortunately, the majority of fine chemicals and pharmaceuticals containing an aromatic ketone moiety is constituted of nonvolatile compounds that decompose when heated at high temperatures for long periods. 

R 598 L. K. Thompson, Unraveling the Secrets of Alzheimer s j3-Amyloid Fibrils , P. Natl. Acad. Sci. U. S. A., 2003,100, 383 R 599 T. Timusk, The Mysterious Pseudogap in High Temperature Superconductors An Infrared View , Solid State Commun., 2003,127, 337 R 600 P. A. Tishmack, D. E. Bugay and S. R. Byrn, Solid-State Nuclear Magnetic Resonance Spectroscopy - Pharmaceutical Applications , J. Pharm. Sci., 2003, 92,441... 

C Hsu, H Nguyen, D Yeung, D Brooks, G Koe, T Bewley, R Pearlman. Surface denaturation at solid-void interface - a possible pathway by which opalescent particulates form during the storage of lyophilized tissue-type plasminogen-activator at high-temperatures. Pharmaceutical Research 12 69-77, 1995. 

Hancock BC, Shambhn SL, Zografi G (1995) Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res 12 799-806 Herschler B, Humer C (2012) FDA new drug approvals hit 16-year high in 2012. Reuters Oiiline. 2012. http //www.reuters.com/article/2012/12/31/us-pharmaceuticals-fda-approvals-idUSBRE8BU0EK20121231. Accessed 31 Dec 2012 Hildebrand J, Scott R (1950) Solubility of non-electrolytes, 3rd edn. Rheinhold, New York Hill TL (1986) An introduction to statistical thermodynamics. Dover, New York House JE (2007) Principles of chemical kinetics, 2nd edn. Elsevier, Amsterdam Khawam A, Flanagan DR (2006) Basics and applications of solid state kinetics a pharmaceutical perspective. J Pharm Sci 95 472 98... 

Hancock BC, Shamblin SL, Zografi G (1995) Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res 12 799-806 Hu Q, Choi DS, Chokshi H, Shah N, Sandhu H (2013) Highly efficient miniaturized coprecipitation screening (MiCoS) for amorphous solid dispersion formulation development. Int J Pharm 450 53-62... 

Another consideration in the selection of technology platform is the polymer chosen for the amorphous solid dispersion formulation. The fact that many pharmaceutical polymers degrade, crosslink, or lose functionality at high temperatures has already been discussed. However, the melt viscosity of a polymer is critical to the ability to extrude the amorphous solid dispersion within the capabilities of the extrusion equipment. The melt viscosity as a function of temperature and shear rate varies considerably across pharmaceutical polymers (Chokshi et al. 2005). Formulation melt viscosities in the range of 10-100,000 Pa s are generally acceptable for HME, although the range depends heavily on the torque limit capability of the particular extruder. 

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