Interest of unstable crystalline forms of API to significantly increase bioavailability of poorly soluble drug - An in-situ molecular complexation approach

摘要

An Active Pharmaceutical Ingredient (API) induces by definition a profitable pharmaceutical effect when interacting with a selected biological target. However, to become a new pharmaceutical drug, APIs need absolutely to reach an enough in-vivo exposure regarding its active pharmaceutical dosage. Moreover, due to practical conveniences, APIs are usually orally administered. So, to be absorbed, APIs have to be firstly soluble in gastro-intestinal fluids and then secondly permeable to gastro-intestinal barriers to reach systemic circulating flow. The permeability is rarely a difficulty in drug development since usually considered by Medicinal chemists as one of selection criteria during the chemical drug optimization. On the counterpart, the solubility in relevant media, being extremely low whatever molecules tested in the Lead Optimization, remains a serious problem to convert APIs in drugs.