Excipient chemical properties

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

Inappropriate use of an excipient can be defined simply as using an excipient in a formulation in a way that ignores certain characteristic properties of the excipient, to the detriment of the formulation performance. It is important to consider all the ways an excipient can interact in a formulation, and then with the physiological fluids after administration of the medicine to the patient. We may include an excipient in a formulation to take advantage of a particular physical or chemical property, but that does not mean that all its other properties are somehow switched off. If not properly considered in the context of the particular formulation, these other properties can cause unexpected problems. 

Excipients bring properties to formulations that facilitate the conversion of the API to a medicine. These functional properties will depend on the particular formulation. For parenteral products, open wound treatments, and ocular treatments, there are specific additional requirements concerning impurities, microbiological load, and endotoxins. However, excipients intended for nonsterile applications very often function, because they are not single chemical compounds. There are other functional or concomitant components frequently present, which are necessary to achieve the required performance (functionality) of the excipient in use. These should be considered separately from any impurities, process residues, or foreign substances that may be present. (In some applications, certain components that have traditionally been considered to be impurities or residues, may actually be concomitant components.) It is important to understand that these other components, whatever their source, may also interact with the API or other excipients. 

Chitosan has been the focus of reasearch as a pharmaceutical excipient due to its specific chemically and biologically favorable features [6-8]. As chitosan is soluble in acidic aqueous solutions, it can be processed under acidic conditions. By contrast, as the product made by chitosan is insoluble at neutral or basic pH, it behaves as a delivery system under such conditions. These chemical properties allow chitosan to control drug delivery. Further,... 

Information about excipients is useful in the initial planning and interpretation of the excipient compatibility results. Important factors to consider for excipients include their physical-chemical properties. The Handbook of Pharmaceutical Excipients lists important information on structure, moisture content, melting point, pH, solubility, and equilibrium moisture at variable relative humidity for individual excipients (27). An example of relevant physical-chemical parameters for some select excipients is detailed in Table 1. A spectroscopic review of excipients (28) has been completed, and extensive reviews of some of the most common types of excipients (i.e., carbohydrate based) are published (29). 

Table 1 Relevant Physical-Chemical Properties of Selected Common Excipients...

However, some excipients have multiple functions. For example, microcrystalline cellulose can function as a filler, a binder, and a disintegrant. As seen in Table 7.3, a typical low-dose formulation could include more than 85% filler—binders. Thus, physical and chemical properties for these specialty excipients are extremely important in a low-dose formulation for manufacturability, product performance, and longterm stability. Because the poor physicomechanical properties of components are not altered during manufacture as they are in the wet or dry granulation process, critical material properties and their impact on product quality attributes should be well characterized and understood.23 Discussion in this section will focus on fillers-binders. For those requiring more information on excipients, several excellent books and review articles are available in the literature.24-27... 

High kneading and dispersing ability can be achieved within the unit independently of the physical and chemical properties of the excipients. 

Changes in the chemical properties of the excipient owing to the change. 

Because key excipients are well established in most new product and process development programs, the same degree of preformulation scrutiny is often not required. Compatibility studies with the API, however, should be performed to study possible untoward interactions between the active ingredients and the excipients. It should be kept in mind that small or minor changes in physical and possibly chemical properties upon intimate contact in binary studies with key excipients should not automatically exclude a favored excipient without further critical testing. 

The formulation and manufacture of tablets involves many processing steps during which the drug substance and excipients are exposed to a variety of stresses. The physical and chemical properties of the API influence the selection of excipients as well as the processing conditions chosen for manufacture. Table 2 contains the typical processing steps in the manufacture of tablets. The possible phase transformations of the API and their implications on product performance are also listed in Table 2. The latter two issues will be discussed in detail later. 

The early tablets (and, unfortunately, many of to-day may be classed with them) were compressed hard, and made without reference to their solubility or to their power to disintegrate, and little skill was required in their preparation. On the other hand, the proper manipulation of the medicinal ingredients, and the choice, proportioning, and manipulation of excipients best suited to use with the different formulas, require a considerable degree of skill, as well as an intimate knowledge of the physical and chemical properties of the ingredients. During... 

The consistency of production may be influenced by quality of the starting materials. Their physical and chemical properties should therefore be defined, documented in their specifications and controlled. Specifications for active starting materials should be as comprehensive as possible, given the current state of knowledge. Specifications for both active and non-active starting materials (excipients) should be periodically re-assessed during development and updated as necessary. 

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