Solids polymorphs

Boggs, J.L. Prentice, K.J. Kraeutle J.E. Crump, The Role of the Scanning Electron Microscope in the Study of Solid Propellant Combustion , inavwepsceiiu ir h/zo yiyoy) do) u,u, Graber, F.C. Rauch A.J. Fanelli, Observation of Solid-Solid Polymorphic Transformation in 2,4,6-Trinitro Toluene , JPhChem 73, (10), 3514—15 (1969) 39) J.E. Crump, J.L. Prentice K.J. Kraeutle Role of Scanning Electron Microscopy in the Study of Solid Propellant Combustion. Part 11—Behavior of Metal Additives , NavWepsCentr TP-5142-PT-2 (1969) 40) J.A. Markham A.R. Cox, Applications... 

The low frequency Raman spectrum of 5CB in the nematic phase and several solid polymorphs is shown in Fig. 13. 

Since the heat absorbed or released by a system at constant pressure is equal to its change in enthalpy, enthalpy is often called heat content. If a phase transformation (i.e. melting or transformation to another solid polymorph) takes place within... 

U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA) (2004, Dec.), Guidance for industry ANDAs Pharmaceutical solid polymorphism chemistry, manufacturing, and controls information, FDA, Rockville, MD. 

FDA(2004).Guidancefor Industry ANDAs Pharmaceutical Solid Polymorphism Chemistry, Manufacturing and Controls Information, CDER, Rockville, MD. 

Rodriguez-Spong, B., Price, C.P, Jayasankar, A., Matzger, A.J., and Rodriguez-Hornedo, N. (2004). General principals of pharmaceutical solid polymorphism a supramolecular perspe tiveQrug Del. Rev., 56 241-274. 

In general, compounds containing N-N02 have more positive heats of formation than those containing C-N02, and multi-cyclic compounds achieve higher density than mono-cyclic. For these reasons, the synthesis of caged nitramines is pursued, and in 1987 Nielsen patented the synthesis of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (HNIW or Cl-20) [64,65]. Like HMX, CL-20 exists in several solid polymorphs, four of which can be isolated at ambient conditions [66, 67]. CL-20 can be... 

A. J. Rodriguez-Hornedo, N. General principles of pharmaceutical solid polymorphism a supramolecular perspective. Adv. Drug. Del. Rev. 2004, 56, 241-274. 

Basic crystal properties include solubility, supersaturation, metastable zone width, oil, amorphous solid, polymorphism, occlusion, morphology, and particle size distribution. Clearly. 

Rodriguez-Spong B, Price CP, Jayasankar A, Matzger 7, and Rodriguez-Hornedo N. General Principles of Pharmaceutical Solid Polymorphism. A Supramolec-ular Perspective. Adv Drug Deliv Rev 2004 56 241-274.. 

Two examples of molecular mobility liberated near two different first-order transitions, namely a solid-solid polymorphic transition and melting, are described ... 

NMR and IR for the analysis of pharmaceutical solids polymorphs of fosinopril sodium. J Pharm Biomed Anal 11 1063-1069, 1994. 

Standard states are simply a special sort of reference state for physical properties, made necessary, as we have mentioned several times, by our lack of knowledge of absolute values for the properties U, G, H, and A. Standard states are therefore systems or states of matter under specified conditions. The definition must be sufficiently complete as to determine the thermodynamic parameters of the substance, and therefore must have at least four attributes 1. temperature 2. pressure 3. composition 4. state of aggregation (solid polymorph, liquid, gas, ideal gas, ideal solution, etc.). Thus 25°C, 1 bar is not a standard state. The question is, what system at 25°C, 1 bar . 

The differences between polymorphs and hydrates are significant. The basis for all these differences is that polymorphs are different crystal structures of the same molecules(s) while hydrates are crystals of the drug molecule with different numbers of water molecules. As discussed above, the hydration state (and therefore the structure) of a crystalline hydrate is a function of the water vapor pressure (water activity) above the solid. Polymorphs, however, are typically only affected by changes in water vapor pressure if water sorption allows molecular motion, which in turn allows a reorganization into a different polymorph (i.e., a solution mediated transformation). This distinction is particularly important in defining the relative free energy of hydrates. A simple (only one molecule) anhydrous crystalline form is a one component system, and the free energy is, practically, specified by temperature and pressure. A crystalline hydrate is a two-component system and is specified... 

Raw AS, Furness MS, Gill DS, Adams, RC, Holcombe Jr FO, Yu LX (2004) Regulatory consideration of pharmaceutical solid polymorphism in abbreviated new drug applications (ANDAs). Adv Drug Deliv Rev 56 397-414. 

FDA Guidance for Industry ANDAs (2007) Pharmaceutical solid polymorphism chemistry, manufacturing, and controls information. 

In the p-alkoxyphenyl esters of cyclohexanedicarboxylic acid, the series was prepared and thermally examined in which the alkoxy group was varied from methoxy through hexyloxy The thermal properties and analytical results for this series are listed in Table 1. The first two members of the series have only nematic mesophases, while the propoxy through the hexyloxy have both nematic and smectic phases As the length of the alkyl tail increases, so does the complexity of the transitions There are four distinct solid polymorphs in the pentyloxy and three in the hexyloxy compound The hexyloxy also has three smectic phases as well as the nematic These three transitions were identified as smectic by microscopy, however no attempt was made to assign them to a particular class The heats of two of these transitions were too small to measure with any degree of accuracy and only the temperatures were recorded Solid polymorphism, such as encountered in these compounds where the transitions occur at very close temperatures, prevents the application of the differential scanning calorimetric method for determination of purity ... 

Table 2 gives the thermal and analytical properties of the series of p-alkylphenyl esters of 1,4-cyclohexanedlcarboxyllc acid. Four members of this series were prepared In which the alkyl group was varied from ethyl through n-pentyl. The first two members, the ethyl and propyl substituted compounds, have straightforward thermal transitions, both showing only enantlotropic nematic mesophases. A smectic phase first appears In the n-butyl member and the butyl and pentyl compounds are both smectic and nematic. The solids In this series are less complex than In the alkoxy series, and there Is no Indication of solid polymorphism. The n-pentyl does become more complex In Its mesophase and three smectics are observed, two of which are monotropic. The transition temperatures of these are too close to allow resolution of the peaks on the DSC, and no determination of the separate heats was made. 

The alkoxy group in this series was varied from methoxy through hexyloxy. The propoxy, however, was not prepared and the values given are from the literature. In this series, which has been examined by several authors, the first four members from methoxy through butoxy are straightforward, and the only mesophase observed was enantiotropic nematic with no solid polymorphism. 

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