Pharmaceutical liquids, compounding

Additives are all formulation constituents other than the active ingredient. Although additives could be classified into excipients and vehicles (excipients for solid preparations and vehicles for liquid ones), there are several other agents used in pharmaceutical formulations with specific functions such as preservatives, sweeteners, coatings, colorants, antioxidants, surfactants, emulsifying agents, and flavors. Since they comprise a vast amount of products, this section will deal with additives for compounding pharmaceutical products for internal use only [17,18]. 

FORMAMIDE. Form amide (meibanamide), HCONHi. is the lirsi member of the primary amide series and is the only one liquid at room temperature. II is hygroscopic and has a faint odor of ammonia. Formamide is a colorless to pale yellowish liquid, freely miscible with water, lower alcohols and glycols, and lower esters and acetone. It is virtually immiscible in almost all aliphatic and aromatic hydrocarbons, chlorinated hydrocarbons, and ethers. By virtue of its high dielectric constant, close to that of water and unusual for an organic compound, formamide has a high solvent capacity lor many heavy-metal salts and for salts of alkali and alkalinc-carth metals. It is an important solvent, in particular for resins and plasticizers. As a chemical intermediate, formamide is especially useful in the synthesis of heterocyclic compounds, pharmaceuticals, crop protection agents, pesticides, and for the manufacture of hydrocyanic acid. 

Table 3.3 lists the molar volume and solubility parameters of pharmaceutical liquids and drug compounds. 

CDs have special properties dependant on their molecular structures. For instance, their hydrophobic cavities can encapsulate organic and inorganic molecules with smaller molecular size to form various inclusion compounds in liquid- or sohd-state forms [3] while their hydrophilic shells can generate noninclusion complexes with larger molecular guests, such as amylose molecules and enzyme molecules [4,5]. Mainly based on the formation of the two kinds of complexes, CDs are widely used in many areas, including foods, pharmaceuticals, cosmetics and personal care industries. 

Liquid chromatography is complementary to gas chromatography because samples that cannot be easily handled in the gas phase, such as nonvolatile compounds or thermally unstable ones, eg, many natural products, pharmaceuticals, and biomacromolecules, are separable by partitioning between a Hquid mobile phase and a stationary phase, often at ambient temperature. Developments in the technology of Ic have led to many separations, done by gc in the past, to be carried out by Hquid chromatography. 

Ring-fluonnated aromatics have found wide applications in pharmaceuticals, crop protection chemicals, polymer intermediates, liquid crystals, etc [10] Routes based on aromatic amines represent one of the major synthetic approaches to these compounds The scope and the techniques have been sufficiently described in reviews [//, I2 and monographs [13, 14, fi] Therefore, only reactions and techniques published after 1971 are discussed... 

Aromatic fluorination certainly is one of the best candidate reactions for micro reactors. Fluorinated compounds are of high industrial interest. For instance, they find wide application as pharmaceuticals, dyes, liquid crystals and crop-protection agents [3,13,16, 38] about every third drug contains a fluorine moiety. The introduction of fluorine moieties in molecules has unique effects on biological activity (see original citations in [16]). 

Thermodynamics of adsorption at liquid interfaces has been well established [22-24]. Of particular interest in view of biochemical and pharmaceutical applications is the adsorption of ionic substances, as many of biologically active compounds are ionic under the physiological conditions. For studying the adsorption of ionic components at the liquid-liquid interface, the polarized liquid-liquid interface is advantageous in that the adsorption of ionic components can be examined by strictly controlling the electrical state of the interface, which is in contrast to the adsorption studies at the air-water or nonpolar oil-water interfaces [25]. 

Ahuja, S., Chemical derivatization for the liquid chromatography of compounds of pharmaceutical interest, /. Chromatogr. Sci., 17, 168, 1979. 

A polymorph is a solid crystalline phase of a compound resulting from the possibility of at least two different crystal lattice arrangements of that compound in the solid state [42], Polymorphs of a compound are, however, identical in the liquid and vapor states. They usually melt at different temperatures but give melts of identical composition. Two polymorphs of a compound may be as different in structure and properties as crystals of two different compounds [43,44], Apparent solubility, melting point, density, hardness, crystal shape, optical and electrical properties, vapor pressure, etc. may all vary with the polymorphic form. The polymorphs that are produced depend upon factors such as storage temperature, recrystallization solvent, and rate of cooling. Table 2 suggests the importance of polymorphism in the field of pharmaceutics [45],... 

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