Low-dose drug products

The development phase for low-dose drug products is similar to any other drug product. At a minimum, the drug product developed should be clinically efficacious, safe, and chemically/physically stable no matter how low the dose strength. Needless to say, scientists who work in chemistry, manufacture, and control (CMC) encounter even more challenges. Therefore, this book focuses on strategies and solutions to the challenges from both theoretical and practical aspects. 

CHALLENGES AND STRATEGIES IN DEVELOPMENT OF LOW-DOSE DRUG PRODUCTS... 

TABLE 1.2 Marketed Oral Solid Low-Dose Drug Products... 

For in vitro dissolution methods, a small volume vessel using 100 mL of medium can also offer a significant sensitivity gain. Nevertheless, equipment modification may be needed to develop analytical methods for low-dose drug products. 

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. 

Figure 2.3 Solid oral formulation decision tree for low-dose drug product (<1 mg).

Sesi NN. 2005. Low-dose drug products analytical challenges and strategies. Annual Meeting of American Association of Pharmaceutical Scientists, Nashville, TN. 

Common problems associated with fluidized bed granulation process for low-dose drug products are ... 

CHALLENGES IN DEVELOPMENT AND SCALE-UP OF LOW-DOSE DRUG PRODUCTS BY DRY GRANULATION ... 

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