Drug-excipient compatibility studies

Formulation profile, which consists of physical and chemical characteristics required for the products, drug-excipient compatibility studies, and the effect of formulation on in vitro dissolution... 

TABLE 10 Examples of Binary and Factorial Designs for Drug-Excipient Compatibility Studies ... 

Understanding the degradation chemistry of drug with excipients is essential to select proper excipients in the formulation stages [16, pp 101-151]. Drug-excipient compatibility studies are crucial to decide optimal tablet formulation and to understand the possible mechanism in many cases [10,12,14], Drug instability occurs by three types of reactions hydrolysis, oxidation, and aldehyde-amine addition. Table 11 gives reaction types of chemical and physical instability. 

In conclusion, drug-excipient compatibility studies have a key role at the early preformulation stages to select excipients or after formulation to help identify the mechanism of any detected instability [14], An understanding of the potential physicochemical interactions of drug with known chemical reactivities of excipients and... 

Although there has been some debate in the literature about the nature of compatibility testing and the value of results (e.g., see Monkhouse and Maderich 1989, and Monkhouse 1993), it is felt that it still has some relevance to pharmaceutical preformulation. Essentially, there are four major stages in drug-excipient compatibility studies, but before considering such studies, it is worth checking whether there are any known incompatibilities, as is shown in Table 6.17 (Monkhouse 1993). 

Thermal methods can be extremely useful during the course of preformulation studies, since carefully planned work can be used to indicate the existence of possible drug-excipient interactions in a prototype formulation [2]. During the course of this aspect of drug development, thermal methods can be used to evaluate compound purity, polymorphism, solvation, degradation, drug-excipient compatibility, and a wide variety of other desirable characteristics. Several recent reviews have been written on such investigations [2-6]. 

Other examples of the use of microcalorimetry to study drug-excipient compatibility in the solid state are provided by Selzer et al. (30), who studied the interaction between a solid drug and a range of excipients [including potato starch, a-lactose-monohydrate, microcrystalline cellulose (MCC), and talc] and Schmitt (31) who used water slurries instead of humidified samples. 

Experimental procedures for running excipient compatibility studies using isothermal microcalorimetry include the collection of power-time curves for each component of the mixture alone, as well as in combinations (Fig. 8). The separate drug and excipient curves can then be used to construct a theoretical non-interaction curve for the blend, which then is subtracted from the actual blend curves in order to define the interaction between the components. 

TABLE 6.4 Total Percentage Impurities for Excipient Compatibility Studies with Drug A or B Stored for 6 Weeks at 40°C/75% Relative Humidity... 

It is recommended that drug substances be evaluated as a solid in a solid-state mixture with potential excipients as part of normal excipient compatibility studies. 

Starch is widely used in the pharmaceutical industry because, among its other properties, it is readily available, inexpensive, white, and inert. Excipient compatibility studies of starch and various active drugs have been performed using thermal methods of analysis. As an example, starch has been found to be compatible with cephalexin and acetylcysteine using this method of excipient screening. 

Compatibility studies are essential in characterizing both raw materials and finished formulations. It has been argued that binary drug-excipient screening studies are inefficient, unrealistic, and ignore processing variables. A better approach may be to carefully select potential excipients based on known chemistry and published compatibility data, and perform miniformulation stability studies. ... 

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