Amorphous-crystalline mixtures

Amorphous materials can be found as hard glassy plastics (polystyrene) or can be soft, flexible and rubbery (polyisoprene). This means that there is a temperature range where an amorphous material is in a glassy state and above which it is rubbery. This temperature is known as the glass-transition temperature Tg. However, a truly amorphous material cannot have a crystalline melting point (Tm). Crystalline materials (usually an amorphous—crystalline mixture) can have a Tg—in the case of polyethylene this is around -85°C. 

As discussed previously, it appears that the as-milled structure in Sm-Co alloys is dependent on the milling conditions. Ding et al. (1994a) and Smith et al. (1996) found that the addition of sufficient Fe to Sm-Co alloys causes the as-milled structure to change from amorphous to a two-phase amorphous-crystalline mixture. 

Lactose normally occurs naturally in either of two crystalline forms— a-monohydrate and anhydrous /3—or as an amorphous glass mixture of a- and /3-lactose. Several other forms may be produced under special conditions. 

This amorphous solid did yield a crystalline structure after 5 months of storage, but the crystals were those of urea only. This is in contrast to simple physical mixtures of the two solids that clearly showed crystalline mixtures of both tolbutamide and urea. In contrast to the tolbutamide-urea system, the tolbutamide-PEG system showed similar degrees of crystallinity for both the rapid-cooled and slow-cooled systems. Dissolution profiles for this system were compared for the rapid-cooled, slow-cooled, and physical mixture samples. The profiles for all three samples were very similar however, the extent of release from the rapid-cooled sample was approximately 10% higher than that of the other two samples at any given time during the dissolution process. 

Solution calorimetry can also be used to evaluate amorphous/crystalline content in a binary mixture. The enthalpy of solution for the amorphous compound is an exothermic event, whereas that of the crystalline hydrate is endothermic. Enthalpy of solution is a sum of several thermal events, that is, heat of wetting (incorporating sorption process, such as surface sorption and complexation), disruption of the crystal lattice, and solvation. The order of magnitude of solution enthalpy for the crystalline compound suggests that the disruption of the crystal lattice predominates over the heat of solvation. In addition, the ready solubility of the compotmd in aqueous media is probably governed by entropy considerations. 

In some solids a degree of disorder remains at absolute zero. Certain pure solids, such as amorphous phases (glasses) and crystalline mixtures, possess a residual entropy. Because of differing molecular orientations (CO) and variations in interatomic bonding (H2O), it holds that S(T = 0)>0. 

Al-sec-butylate A1(N03)39H20 ai2o3 colourless amorphous crystalline forms mixtures with other oxides... 

Rapid form dissociation and precipitation of known forms of the parent celecoxib was observed in 0.1 N HCl, SGF, 0.02 N HCl, pH 6.5 phosphate buffer and pH 6.5 phosphate buffer with sodium dodecyl sulfate (SDS). The initial dissolution rate was found to be superior for the co-crystal versus the stable form of the parent compound, but rapid conversion to aggregated crystalline celecoxib made this co-crystal a poor candidate for direct use as a dosage form. This initial dissolution advantage was exploited further by formulating the co-crystal with PVP-K30 and the ionic surfactant SDS. Using this combination of excipients, the co-crystal was repeatedly observed to precipitate as a poorly crystalline mixture of metastable celecoxib form 4 and amorphous material. Although the co-crystal was not tested in vivo, the in vitro performance improvements are consistent with improvements observed in other celecoxib formulations with demonstrated in vivo advantages over Celebrex . 

FIG. 4 Plots of vapor pressure of the crystalline substances versus the time required to become amorphous in mixtures with activated carbon. (O) At 25°C and atmospheric pressure ( ), at 40°C and reduced pressure. 1, Benzoic acid 2, o-hydroxybenzoic acid 3, w-hydroxybenzoic acid 4. p-hydroxybenzoic acid 5, o-chlorobenzoic acid 6, m-chlorobenzoic acid 7, p-chlorobenzoic acid. (From Ref. 13.)... 

The preceding remarks relate to amorphous polymer mixtures. Not all polymers or their blends are totally amorphous and PCL blends provide a major set of examples of semi-crystalline, as well as amorphous, blends, often in the same system. It is therefore necessary to consider some thermodynamic consequences of crystallinity in blends. 

Hoei Y, Yamaura K, Matsuzawa S (1992) A lattice treatment of crystalline solvent-amorphous polymer mixtures on melting-point depression. J Phys Chem 96(26) 10584-10586 Hrub A (1972) Evaluation of glass-forming tendency by means of DTA. Czechoslov J Phys B 22(11) 1187-1193... 

The point is this. Use of the term co-crystal in the introduction, or preamble, of a patent claim defines the type of composition being claimed. First, defining the claimed composition as a co-crystal refers to the solid state and excludes amorphous materials. Second, it is a co-crystal and therefore distinct from a non-crystalline mixture or a salt, a crystalline solvate, or other prior art combinations of the API and co-former (should they exist). While a general preamble may not affect the scope of a claim, the preamble of a claim when used to define a substance to the exclusion of others may in fact limit the scope of the claim. Thus, the purpose and effect of an inventor using the term cocrystal to define the relationship between the API and co-former in the composition should be considered not only for what it includes, but also for what it excludes. This can be a useful defitional boundary to focus on what is the patentable subject matter and why it is patentable. 

The NMR method was used to determine the evolution of the amorphous fraction in a trehalose powder, during a milling procedure which ultimately leads to a fully amorphous state. The purpose of the study was to determine quantitatively the amorphous fraction in crystalline-amorphous powder mixtures of trehalose, in order to assess the ability of the C NMR technique for quantitative amorphous characterisation. Poly(ethylene oxide) (PEO) was tested as a polymer matrix for solid dispersion to enhance drug bioavailability. Solid-state NMR, X-ray diffraction, and transmission electron microscopy were utilised to characterise the high miscibility between PEO and ketoprofen, a model for crystalline drugs with poor water solubility. ... 

Suitable theoretical models (e.g., the Havriliak-Negami (HN) model [24]) for analyzing the relaxation behavior of polymer blends (including amorphous/crystalline and thermosetting polymer mixtures) as a function of composition, temperature, crystallization and curing times can be used to evaluate the dielectric relaxation strength of a particular relaxation process and provide suitable information about the number of segments that contribute to the different relaxation processes. In... 

Studies similar to those described above can be carried out on polyamides [207] and polyurethanes [208, 209]. Moreover, infrared spectroscopy has been used to study intermolecular interactions in amorphous /crystalline binary blends such as mixtures of poly(caprolactone) [210] or (polyethylene oxide) [211] and poly(vinylphenol). 

Figure 4.7 Various representations of the properties of a mixture of crystalline and amorphous polymer, (a) The monitored property is characteristic of the crystal and varies linearly with 0. (b) The monitored property is characteristic of the mixture and varies linearly with 0 between and P, . (c) X-ray intensity is measured with the sharp and broad peaks being P. and P., respectively.

When the reaction mixtures are prepared from colloidal siUca sol or amorphous siUca, additional 2eohtes may form which do not readily crystalline from the homogeneous sodium siUcate—alurninosiUcate gels. The temperature strongly influences the crystallization time of even the most reactive gels for example, zeoHte X crystallizes in 800 h at 25°C and in 6 h at 100°C. 

The only clearly defined crystalline compositions are three forms of phosphoric acid and hemihydrate, pyrophosphoric acid, and crystalline P O q. The phosphoric acids obtained in highly concentrated solutions or by mixing phosphoric acid with phosphoms pentoxide are members of a continuous series of amorphous (excluding [Y OO]) condensed phosphoric acid mixtures. Mixtures having more than 86% P2O5 contain some cyclic metaphosphoric... 

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