Solid state stability characterization

Matsuda, Y. and S. Kawaguchi. 1986. Physicochemical characterization of oxyphenbutazone and solid-state stability of its amorphous form under various temperature and humidity condEtlrota. 

Solid-state characterization is one of the most important functions of the preformulation group, which is assigned the responsibility of making recommendations for further formulation work on a lead compound. Physical properties have a direct bearing on both physical and chemical stabilities of the lead compound. Much of the later work on formulation will depend on how well the solid state is characterized from the decisions to compress the drug into tablets to the selection of appropriate salt forms. The studies reported in this section, of course, apply to those drugs that are available in solid form, crystalline or amorphous, pure or amalgamated. 

The alkylruthenium species obtained in eq. 5.1 is very stable in water, neither the addition of strong acids nor boiling for several hours lead to its decomposition. In aqueous solution it exists as a monomeric cation, however, it was isolated in solid state and characterized by X-ray crystallography as a dimer [ Ru(C2H5)(C0)2(H20)2 2]2+. The stability of this ruthenium alkyl is attributed to the stabilization effect of strong hydrogen bonds which could be detected in the crystal structure and are postulated also in its aqueous solutions. Finally, elimination of propionic acid from the acyl could be induced by raising the temperature this reaction closes the catalytic cycle ... 

Some early applications and potential benefits of the technique were described by Bolton, Prasad, and co-workers [2-5]. Highlighting an area where Raman spectroscopy currently provides valuable data, these workers showed how the lattice vibrations (or phonons) are of considerable value in the characterization of solid states of a drug and especially for the investigation of polymorphism. In addition to examining solid-state stabilities of crystalline modifications to drug crystals, the value of the technique for researching solute-solvent interactions of pharmaceutical materials was also demonstrated. 

Solid-state C NMR techniques have been applied to the characterization of the different phases of several polybibenzoates [25,30], including P7MB, PDTMB and PTEB. The last two polymers offer the advantage of the stability of the mesophase at room temperature. The spectra corresponding to the pure mesophase of these samples only exhibited a broad component, while the spectra of the annealed samples were separated into two components crystal and noncrystal. The shapes of the mesophase and the noncrystal components are very similar, and only modest variations in the relaxation times were observed between these two components. The degree of crystallinity of these samples was determined... 

Reliable information on the thermodynamic stability of group 13/15 adducts is usually obtained by gas phase measurements. However, due to the lability of stibine and bismuthine adducts in the gas phase toward dissociation, temperature-dependent H-NMR studies are also useful for the determination of their dissociation enthalpies in solution [41b], We focussed on analogously substituted adducts t-BusAl—E(f-Pr)3 (E = P 9, As 10, Sb 11, Bi 12) since they have been fully characterized by single crystal X-ray diffraction, allowing comparisons of their thermodynamic stability in solution with structural trends as found in their solid state structures. 

Catalano et al. reported the synthesis and characterization of a new series of Pd°-based metallocrypates that bind Tl1 ion in the absence of attractive ligand interactions through metal-lophilic connections. The cationic species have been characterized by a variety of methods and have considerable stability. From the solid-state structural data it is apparent that interaction of the metal atoms with one another is the dominant bonding interaction within the metallocryptate cavity. The characterization of complexes supports the concept of metallophilic behavior as a fundamental component of bonding in closed-shell systems. These materials may ultimately serve as prototypical systems for detection of closed-shell ions 946... 

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