Emerging nanonisation technologies: tailoring crystalline versus amorphous nanomaterials

Abstract

The overall pharmaceutical market is changing. A more personalised medicine approach is replacing the concept of blockbuster drugs and the “one size fits all” model. The two main forces that fuel the growth of nano-enabled drug technologies are the low aqueous solubility of new chemical entities and the pharmaceutical market itself, as the development of novel drug delivery systems can extend the drug patent lifetime. Classical solubilisation techniques, such as salt formation and the use of cyclodextrins can only be applied to drugs with ionisable groups or specific molecular weight ranges in order to fit in the cavity of the cyclodextrin. However, drug nanonisation, or particle size reduction into the nanosize range, is a versatile technique that can be applied to a wide range of pharmaceutical compounds. Nano-drugs exhibit higher surface area per unit of volume, which leads to faster dissolution kinetics and hence potentially improved bioavailability. Marketed nano-drugs are mostly crystalline due to the improved physical stability afforded by the crystalline state whereas amorphous nano-drugs have been largely neglected in spite of generating higher saturation solubility compared to their crystalline counterparts. Due to the vast potential in the global pharmaceutical market, many technologies have been licensed to produce nano-drugs. Among them, the most successful by far is Nanocrystal® Technology based on wet milling methods. In this review, the main methods to generate and characterise nano-drugs are covered and also, the biopharmaceutical characteristics of the marketed nano-drugs are discussed