Practical Solutions For Poorly Soluble Drugs

The therapeutic efficacy of a drug depends upon its bioavailability, which is directly correlated to its solubility. Many drugs, both in development and on the market, are poorly soluble in aqueous media, which can lead to poor bioavailability and frequently results in variable dissolution rates. To achieve the desired drug concentration in systemic circulation to elicit a pharmacological response, solubility is paramount. Yet, less than 10% of new drug candidates demonstrate both high solubility and permeability, and 30–40% of the drugs that appear on the World Health Organisation (WHO) Essential Drug List were reported to be poorly water-soluble or lipophilic, based on the Biopharmaceutics Classification System. Solubility depends on the physical form of the solid, the nature and composition of solvent medium as well as the prevailing temperature and pressure. There are various techniques available to improve the solubility of poorly soluble drugs.

Compared with highly soluble compounds, low drug solubility can manifest itself in a variety of unwanted consequences, including (in vivo) decreased bioavailability, an increased chance of a food effect, incomplete release from the dosage form and high inter-patient variability. In vitro, as well, issues such as limited delivery technologies and complex dissolution testing with limited or poor correlation to the in vivo absorption can be problematic. Obtaining predictable and reproducible in vivo/in vitro correlations is vital to the successful development of any newly synthesised compound with solubility issues.