Amorphous dispersions

With the aid of X-ray diffraction, it was observed that the formation of amorphous dispersion, instead of crystalline dispersion of drug, in the drug-excipient solid solution contributed to quicker dissolution and a higher amount of total drug release in the dissolution test. Furosemide (Fig. 2) was shown to form amorphous dispersions in the solid solution with either polyvinylpyrrolidone (PVP) or crospovidone, as evidenced by X-ray diffraction (26,27). The extent of amorphous dispersions... 

Zeolite crystallization can be interpreted in terms of a ripening mechanism. The initially formed gel consists of amorphous dispersed particles of the order of 100-300 A in size. Growth of these particles to approximately 1000 A occurs during the induction period after which zeolite crystals appear imbedded in the amorphous gel matrix. This is especially evident in electron microscopic studies of gel solids (66,88). Ciric comments on the observation of growing crystals imbedded in gel particles which, as the crystals grow, tend to shrink together, resulting in coalescence (74)-... 

Source Appel, L.E., et al., Controlled release by extrusion of solid amorphous dispersions of drugs, US Patent 6706283, 2004. 

Thus, as follows from the analysis of d(T) dependence of amorphous dispersion, the polymer chain tacticity breakdown causes changes of packing in two directions only, where the long-range order is not realized, but the interplanar spacing is unaffected. 

Precambrian cherty iron sediments. Data on diagenetic processes that went on in ancient rocks which have not retained their original form can be obtained only indirectly, on the basis of a number of assumptions. In any version of the chemogenic hypothesis, the original cherty iron sediment must have been amorphous-dispersed, and the processes of diagenesis were an important step in the formation of the crystalline rock. However, it is quite unclear whether essential mineral transformations occurred, or whether diagenesis was limited to recrystallization of the original sedimentary miner-... 

Therapeutic proteins typically exist in a noncrystalline or amorphous form because their macro-molecular structures are not readily crystallized. These materials are commonly prepared in an amorphous dispersion with bulking and stabilizing excipients to ensure an adequate product shelf life and ease of administration. Examples of such therapeutic proteins include insulin and interferon. 

Reduction of particle size. In the case of glass, solid solutions, and amorphous dispersions, particle size is reduced to a minimum level. This can result in an enhanced dissolution rate due to an increase in both the surface area solubilization. 

Lowinger, M., H.H. Tung, H.C. McKelvey, Z. Liu, and W. Wu (2007). Investigating molecular interactions between drug and polymer molecules in soUd amorphous dispersions. Presented at the Colloid and Suiface Science 81st Symposium, Newark, DE, June. 

Similar behavior has been observed for noncrystallizing polymers. For example, the diffusivity of water in poly(vinylpyrrolidone) (PVP) (Oksanen and Zografi, 1993) has been shown to increase at water contents beyond the hydration limit. Additional reports have shovm that the hydration limit has physical significance for other polymer excipients. Microcrystalline cellulose and lactose for compression, for example, lose their direct compaction properties at water contents just below (Huettenrauch and Jacob, 1977), and gelatin capsules become brittle as the water content is reduced below Wm (Kontny and Mulski, 1989). Recently, the chemical stability of a model peptide in PVP matrices was shown to improve when the amorphous dispersion was stored below the polymer s hydration limit (Lai et al., 1999a Lai et al., 1999b Lechuga-Ballesteros et al., 2002). 

The catalytic activity was investigated for the total oxidation of methane and chloromethane as testing reactions. Selected results are presented in Fig. 2 and Fig. 3 Compared with the impregnated MnOx/ZrOz catalysts the catalytic activity of the precipitated catalysts for the methane conversion is higher [15]. The best results were obtained for MnOx loadings between 20 and 40 mol% (Fig. 2). With respect to the structural investigations it is suggested that the amount of X-ray amorphous (dispersed) MnOx species on the ZrOz surface is responsible for the catalytic activity. Moreover, with... 

Blends with a Crystallizable Matrix and an Amorphous Dispersed Phase... 

Huang J, Wigent RJ, Schwartz JB (2008) Drug-polymer interaction and its significance on the physical stability of nifedipine amorphous dispersion in microparticles of an ammonio methacrylate copolymer and ethylcellulose binary blend. J Pharm Sci 97 251-262. 

Deuterium-exchange measurements have shown that various types of amorphous dispersed silica contain not only surface hydroxyl groups but also structurally bound water inside the silica skeleton and fine ultramicropores. According to infrared spectral measurements [53], such bound water consists of silanol groups inside the silica sample (the adsorption band of stretching vibrations is about 3650 cm ). The distribution of OH groups between the surface and the bulk of the sample depends on a number of factors, but mainly on the method of preparation of the silica sample and its subsequent treatment. 

FIGURE 49.4 Spring and parachute performance of amorphous dispersions in comparison to crystalline material. 

In the absence of solubility, drug substances are poorly absorbed in vivo leading to ineffective therapies. One strategy to address this is the formation of an amorphous dispersion that leads to higher solubility and faster dissolution rates, whereby the drug substance becomes more bioavailable. 

Typically such amorphous dispersions are prepared by melt extrasion (i.e., cooling from a melt) [79], spray drying [80], or lyophilization [81]. Although the reliable... 

Shown in Figure 13.10 is a comparison of the probability distributions for the carboxylic acid (—COOH) HB donor in IMC to form HBs at different HB acceptor sites in amorphous IMC (white bars) and in an amorphous IMC-PVP (58 41) dispersion (black bars) obtained in the MD simulations at 298 K [32]. A representative structure of an IMC-PVP HB is also shown (only a portion of a PVP chain is included). Previously it has been suggested that the inhibition of cyclic dimer formation that is necessary for nucleation of the most stable y-crystaUine form in the presence of PVP is a major factor in the inhibition of IMC crystallization in IMC-PVP amorphous dispersions [31]. The results of MD simulations appear to support this argument The probability that the HB from a given IMC carboxylic acid is to another IMC molecule was found to shift from greater than 90% in amorphous IMC to less than 20% in the presence of 41% w/w PVP. Nearly 80% of the —COOH HBs... 

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