Dr. Watts works with development-focused pharmaceutical researchers in academia and industry in advancing drug products through the preclinical stage. Projects range from early stage physicochemical characterization to in vivo efficacy and safety. Specific emphasis has been placed on development and testing of inhaled formulations including initial aerosol characterization, preclinical efficacy models, and GLP inhaled toxicity.
Localized Treatment of Pulmonary Indications – Asthma and Chronic Obstructive Pulmonary Disease (COPD) are often treated with drugs that reduce inflammation and/or inhibit airway constriction. Current classes of drugs for these indications include corticosteroids, muscarinic antagonists, beta2 agonists, and leukotriene inhibitors. While these drugs have proven effective in marketed inhaled products, poor control over inhaled dose, unwanted side effects, and development of drug resistance remain a major limitation of inhaled therapies. In pediatric populations, these issues are of greater concern and are compounded by administration difficulties. New research focused on reformulation of current therapies to reduce dose-limiting side effects, modifying drug release profiles, and target drug delivery has begun to improve inhaled therapeutics.
Improving Bioavailability of Poorly Water Soluble Drugs – It is commonly cited that nearly 40% of new compounds identified for therapeutic use exhibit poor aqueous solubility. Many techniques have been used to improve water solubility including particle size reduction, solid dispersion processes, molecular complexation, and self emulsifying systems. Of particular interest is the stabilization of amorphous drug in a suitable pharmaceutical carrier to improve drug solubility and, ultimately, bioavailability.
Efficacy Studies in Preclinical Models of Airway Disease – Prior to conducting clinical trials for a new inhaled therapy, the drug product must be proven efficacious in one or more animal models. New treatments for airway disease are typically evaluated in a sensitized rodent model that will exhibit pulmonary inflammation and constriction similar to that encountered in asthma and COPD. A better understanding of the effects of novel formulations, methods of dose administration, sensitization, and response quantification are needed in these models.
Pharmacotherapy to Prolong Allograft Survival in Transplant Recipients – Following organ transplant, patients are prescribed a multi-drug regimen consisting of immunosuppressive drugs such as corticosteroids, calcineurin inhibitors, and antimetabolites. These transplant therapies are often complicated by opportunistic infection and reduction in patient quality of life due to untoward side effects. Advanced drug formulation and delivery to localize therapy and reduce side effects shows potential to improve outcomes of lung transplant recipients.