R. M. Shanker1
1Pfizer Inc, Pharmaceutical Science, Worldwide R&D, Groton, CT, 06340, USA
Low aqueous solubility resulting in poor oral bioavailability of new molecular entities has been recognized as one of the most common physicochemical property challenge that the pharmaceutical industry has encountered in recent years1-5. The wide spread prevalence of this problem has provided opportunities to the pharmaceutical scientist as well as drug delivery technology companies to advance multiple approaches to solubilize such molecules to enhance their oral bioavailability6-9. Solubilization techniques have been based on the following approaches10 (a) formation of salts for ionizable compounds11-12 and co-crystals for ionizable and non-ionizable drugs (b) solvent, cosolvents and lipids13-16 (c) micellar, polymeric micelle systems including self emulsifying drug delivery systems (SEDDS)17-22(d) particle size reduction including the use of attrition milled nanocrystalline forms23-28 (e) complexation29-31 (f) prodrugs32-34 and (g) amorphous solids and solid dispersions35-42. A central theme governing the success of all the above listed solubilization technologies is their ability to create a “supersaturated” solution relative to the intrinsic aqueous solubility of the insoluble compound42. Supersaturated solutions are metastable. Thus a scientifically intriguing as well as technically challenging task for the formulation scientist is to understand the thermodynamic instability of the supersaturated solution but design with confidence a kinetically stable and reproducible system in order to achieve the goal of enhancing oral bioavailability of poorly water soluble compounds. The formulation scientist faces innumerable challenges such as: Selecting the preferred solubilization technology for the compound of interest; what is the degree of solubilization necessary? What future research would enable better efficient selection of preferred solubilization technology with high degree of confidence? This presentation will attempt to address these questions.