Cyclopentadienyl‐steroide 6. Mitt. über farbige Steroide

Abstract

H i i t t e n r a u c hArchiv der Pharmazie 2338. R. Hiittenrauch Cyclopentadienyl-steroide 6. Mitt. iibm farbiee Steroide l) Am den Wissensohaftlichen hboratorien des VEB Jenapharm, Jena Nach der Kuhnachen Regel besitzen Polyene eine Farbe, wenn sie mehr a h sechs konjugierte Doppelbindungen enthaltena) 8 ) . Ein Konjugationssystem besonderer Art bilden die beiden Doppelbindungen des Cyclopentadiens. Ihr Vorkommen in einer Molekiilstruktur kann bereits geniigen, um einer Verbindung Farbe zu verleihen. Diese Ausnahmeerscheinung wird durch das Streben des Fiinfrings nach einem 6 n-Elektronenmtand erklart. Das Cyclopentadienylanion besitzt pseudoaromatische Struktur*), in der das freie Elektronenpaar keinem bestimmten C-Atom zugeordnet werden kann und die Ansbildung mesomerer Grenzformen hervorruft : Dieses hochsymmetrische n-Eiektronensextett bestimmt auch das ausgepragte Kondensationsvermogen des Cyclopentadiens. Bei seiner Entstehung fungiert ein OH-Anion ah Acceptor.Erstmalig gelang ea !l' hieZe6) 6), die durch zwei gekreuzte Doppelbindungen aktivierte Methylengruppe mit Carbonylverbindungen zu kondensieren. Die Reaktion entapricht einer Aldoladdition, bei der das nucleophile Cyclopentadienylanion die im Alkalischen polarisierte Oxogruppe anpjft. s, J . Thielc, Ber. dtech. chem. &a. 33,666 (1900).

Characteristics and Significance of the Amorphous State in Pharmaceutical Systems

“…If a small amount of amorphous structure is introduced into a crystalline sample by processing 3,4,104 and this is deemed to be undesirable, raising the operating temperature above T g , or exposing the sample to elevated relative humidity so as to lower T g , can "anneal" the sample back to a completely crystalline state. An important question with regard to crystallization is, At how low a temperature must an amorphous sample be stored to provide typical 3-5 year shelf-life stability?…”

“…For example, for a crystalline drug with very poor aqueous solubility, the formation of a coamorphous mixture with a water soluble additive can provide an opportunity to enhance dissolution and perhaps bioavailability. 4,95 Additionally many excipients come to the formulator in a fully or partially amorphous state (e.g., microcrystalline cellulose, starch, poly(vinylpyrrolidone)), and other excipients may be purposefully rendered amorphous to enhance functionality (e.g., spray-dried lactose).…”

“…Partially ordered systems have traditionally been described using either "one-state" or "two-state" models. 4,28,41,42 In the two-state model, domains of material are assumed to be either 100% amorphous or 100% crystalline and they coexist side by side in a molecular mixture. This type of system can be simulated to some extent by making physical mixtures of reference samples of crystalline and amorphous materials.…”

“…At T g the properties of the glassy material deviate from those of the equilibrium supercooled liquid to give a nonequilibrium state having even higher H and V than the supercooled liquid. As a result of its higher internal energy (e.g., ≈25 kJ‚mol -1 for cephalosporins 3 ) the amorphous state should have enhanced thermodynamic properties relative to the crystalline state (e.g., solubility, 4 vapor pressure) and greater molecular motion. We would also expect amorphous systems to exhibit greater chemical reactivity 3 and to show some tendency to spontaneously crystallize, possibly at different rates below and above T g .…”

“…5 From a pharmaceutical perspective we have an interesting situation. The high internal energy and specific volume of the amorphous state relative to the crystalline state can lead to enhanced dissolution and bioavailability, 4 but can also create the possibility that during processing or storage the amorphous state may spontaneously convert back to the crystalline state. 5 In considering the importance of the amorphous state in pharmaceutical systems we must direct our attention to two main situations.…”