By Kimberly Shepard, Ph.D., Associate Principal Engineer
Lung cancer, the leading cause of cancer-related deaths worldwide, has proven challenging to treat for several reasons. Most lung cancer treatments are administered systemically—whether by injection, intravenous (IV) infusion, or orally—and often are poorly tolerated by patients. The blood drug levels required for adequate lung tissue exposure are high enough that adverse effects are common, and severe toxicity can preclude the use of some highly potent compounds altogether. In addition, the method of administration makes treatment challenging. Many treatments—by IV infusion, for example—must take place in a clinical setting, leading to high costs, inconvenience, and challenges in patient compliance.
Inhaled formulations offer an ideal means to overcome these challenges through site-specific (i.e., local) treatment of lung cancer. Local delivery overcomes the disadvantages of systemic administration using well-established devices such as dry-powder inhalers (DPIs), which can deliver medicine directly to the lungs. Issues with treatment convenience, expense, and compliance are overcome, since these devices are easy to use, maintain product stability at ambient conditions, and can be self-administered at home. This is especially advantageous because lung cancer therapeutics are often administered indefinitely as maintenance treatments.
Here, we describe formulation and manufacturing considerations for development of dry-powder therapeutics for local treatment of lung cancer. A case study is presented in which an approved drug—topotecan—is successfully formulated for DPI administration to the lung.