Drug-excipient compatibility

Incompatibilities have also been observed in solid dosage forms. A typical tablet contain binders, disin-tegrants, lubricants and fillers. Compatibility screening for a new drug should consider two or more excipients from each class. Serajuddin et al. have developed a drug-excipient compatibility screening model to predict interactions of drug substances with excipients [49],... 

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]. 

Serajuddin, A.T.M., Thakur, A.B., Ghoshal, R.N., Fakes, M.G., and Varia, S.A., Selection of solid dosage form composition through drug-excipient compatibility testing, /. Pharm. Sci., 88, 696, 1999. 

However, as might be anticipated, there is no universal panacea to drug stabilisation. Basic excipients can also destabilise formulations. Serajuddin et al. [19] reported on the drug-excipient compatibility of a calcium channel... 

Serajuddin, A. T. M., A. B. Thakur, R. N. Ghoshal, M. G. Fakes, S. A. Ranadive, K. R. Morris, and S. A. Varia. 1999. Selection of dosage form composition through drug-excipient compatibility testing. 

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... 

Sims JL, Carreira JA, Carrier DJ, Crabtree SR, Easton L, Hancock SA, Simcox SR. A new approach to accelerated drug-excipient compatibility testing. Pharm Dev Technol 2003 8(2) 119-126. 

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. 

Wissing S, Craig DQM, Barker SA, Moore WD. An investigation into the use of stepwise isothermal high sensitivity DSC as a means of detecting drug-excipient compatibility. Int J Pharm 2000 199 141-150. 

Serajuddin A, Thakur A, Ghoshal R, Fakes M, Ranadive S, Morris K, Varia S. Selection of solid dosage form composition through drug-excipient Compatibility Testing. J Pharm Sci 1999 88(7) 696-704. 

Some excipients contain a certain amount of amorphous form such as spray-dried lactose,27 and others are hygroscopic, such as microcrystalline cellulose.28 These excipients will adsorb water, which causes a change in the micro-environment of the formulation. If the drug substance is moisture-sensitive, degradation may occur quickly. Therefore, consider both drug-excipient compatibility and excipient impurity profile in selecting excipients for low-dose drug products. 

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... 

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