Amorphous pharmaceutical materials examples

Table 1 Examples of some amorphous pharmaceutical materials...

Different localized levels of molecular order can coexist in some pharmaceutical materials, giving rise to the occurrence of partially crystalline (and partially amorphous ) systems. In most cases, the properties of such materials (e.g., density) are intermediate to those of the 100% amorphous and 100% crystalline samples. By deliberately varying the level of crystallinity in such systems, their properties can be customized for a particular purpose. An example of this is with the tableting excipients microcrystalline cellulose and spray-dried lactose, which have had their compression characteristics optimized by manipulating their amorphous content. The properties of partially crystalline materials may be approximated in many instances by making physical mixtures of the totally amorphous and crystalline samples. This is known as the two-state model for partially crystalline systems.However, such experiments should be undertaken with caution as the mixed two-state material can sometimes have significantly different properties from the partially crystalline material that is manufactured directly (the real one-state system). ... 

For pharmaceutical materials moisture is known to affect a wide range of properties such as powder flow compactibility and stability (physical chemical and microbiological) (8 46-53). The interaction between moisture and a solid is complex and can occur in a variety of ways. For example water can be stoichiometrically incorporated into a solid s crystal structure in the form of a hydrate (pseudo-hydrate) as discussed previously in this section. In addition moisture can have non-stroichiometrical i.e., nonspecific interactions with a solid by adsorbing on the surface or being absorbed into the material and acting as a plasticizer. These non-specific interactions are more common in amorphous or semi crystalline materials and are the subject of this section. 

Another physical property that can affect the appearance, bioavailability, and chemical stability of pharmaceuticals is degree of crystallinity. Amorphous materials tend to be more hygroscopic than their crystalline counterparts. Also, there is a substantial body of evidence that indicates that the amorphous forms of drugs are less stable than their crystalline counterparts [62]. It has been reported, for example,... 

A great many of the materials that are used as pharmaceutical excipients occur naturally in the amorphous or partially amorphous state (e.g., gelatin and starch). Many others have been found to possess improved handling and mechanical properties when processed in such a manner as to render them at least partially amorphous. Examples of this include the grades of microcrystalline cellulose and lactose monohydrate used as pharmaceutical tableting diluents. ° ... 

To illustrate the ARS form selection process, two pharmaceutical examples of ARS form selection are provided. Indinavir sulfate is the API for Crixivan , a specific and potent inhibitor of the HIV-1 protease used in the treatment of AIDS. Indinavir sulfate is produced as a crystalline ethanolate sulfate salt. If the material is stored in double polyethylene liners within fiber containers or repeatedly exposed to ambient conditions changes occur in both crystallinity and solvation. Using XRPD, KF, and RP-HPLC, conversion of the crystalline ethanolate to amorphous material or to a hydrate crystal form has been detected and degradation is observed. However, the material is stable if stored in a tightly sealed container impermeable to ethanol/moisture transport under an inert nitrogen atmosphere at a controlled room temperature.82,83 These storage conditions are not practical for a routinely used ARS. Therefore, the free base monohydrate form of indinavir sulfate was evaluated and selected as the ARS. This form of the API was demonstrated to be extremely stable under ambient conditions needed for routine analysis. 

In this presentation, two examples of the use of vibrational spectroscopy to probe water-solid interactions in materials of interest to the food and pharmaceutical sciences are described. First, the interaction of water vapor with hydrophilic amorphous polymers has been investigated. Second, water accessibility in hydrated crystalline versus amorphous sugars has been probed using deuterium exchange. In both of these studies, Raman spectroscopy was used as the method of choice. Raman spectroscopy is especially useful of these types of studies as it is possible to control the environment of the sample more easily than with infrared spectroscopy. 

P-Cyclodextrin and its derivatives have been shown to form amorphous lyophilized products with a number of compounds, principally nonsteroidal antiinflammatory agents. Examples from the literature of excipients and pharmaceuticals prepared as amorphous materials by lyophilization are given in Table 7. 

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. 

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