Amorphous pharmaceutical materials applications

This article provides an overview of the properties and occurrence of amorphous pharmaceutical materials, and outlines their key applications in dosage form development. It describes their characteristics and the fundamental scientific basis for these characteristics. It also highlights the topical issues of chemical/ physical stability and polyamorphism. ... 

Thermal analysis is an extremely important analytical tool for the pharmaceutical industry. All transitions in materials involve the flow of heat (either into the sample during an endothermic event or out of the sample during an exothermic event) and DSC is the universal detector for measuring a wide variety of transitions in pharmaceutical materials. These include measurement of amorphous structure, crystallinity (and polymorphs), drug-excipient interaction and many other applications. 

R 327 M. Auger, Biological and Pharmaceutical Applications of Solid-State NMR Spectroscopy , Can. J. Anal. Sci. Spect., 2002, 47,184 R 328 K. Awazu and H. Kawazoe, Strained Si-O-Si Bonds in Amorphous SiOa Materials A Family Member of Active Centers in Radio, Photo, and Chemical Responses , J. Appl. Phys., 2003,94, 6243 R 329 T. Babadagli and S. Al-Salmi, A Review of Permeability-Prediction Methods for Carbonate Reservoirs Using Well-Log Data , SPE Reserv. Eval. Eng., 2004, 7, 75... 

Low density polyethylene material has branched chains and limited crystallinity, which lead to an open structure and the low density. It is particularly soft and flexible, transparent to translucent, has good impact resistance and relatively low melting points, which give good heat sealability. Most LDPEs are made by a high pressure polymerisation process starting from ethylene gas. The proportion of crystallinity to amorphous is around 3 2 (i.e. 60-65% crystalline). Recently new linear polyethylene copolymers of 0.89-0.91 (ultra or very low densities) have been developed. Special antioxidant free grades are available for pharmaceutical applications. 

Organic zeolite analogues are commonly referred to as porous solids. These materials promise a new range of applications, e.g., in pharmaceutical manufacture and in molecular sieves, sensors, and devices. They are crystalline or amorphous materials that permit the reversible passage of molecules through holes on their surface. Porous solids are classified according to pore diameter nanoporous or microporous (< 15 A), mesoporous (15—500 A) and macroporous (>500 A). The natural and synthetic inorganic zeolites with uniform pore sizes of 10-20 A are the classical examples of microporous materials with widespread use in industry. 

Various examples of solid-state NMR applications are collected in the final Section 4. This section is divided into 13 subsections depending on the type of the material studied (4.1) organic solids (4.2) inclusion compounds (4.3) amino acids and peptides (4.4) proteins (4.5) pharmaceutical and biomedical applications (4.6) polymers (4.7) carbonaceous materials (4.8) organometallic and coordination compounds (4.9) glasses and amorphous solids (4.10) micro- and mesoporous solids (4.11) surface science and catalysis, and (4.12) inorganic and other related solids. 

Cycloolefin (CO)Polymers. Many metallocenes can incorporate bulky cycloolefins into polyethylene, but only a few companies, notably Hoechst and its successor Ticona, have attempted to sell the resulting materials. These glassy, amorphous copol5miers have high rigidity, chemical resistance, and clarity, which predisposes them to be useful in optical applications and in pharmaceutical containers. 

Despite extensive research and advancement in this area, application of ASD technology has not gained widespread use in the pharmaceutical industry, and still remains a niche technology applicable only to small number of compounds. The primary reasons for this reluctant adoption can be attributed to fear over the inherent physical instability of the amorphous material during manufacturing, storage, and dissolution, as well as lack of accessibility of robust and commercially viable manufacturing facilities. 

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