Disordered drug delivery: destiny, dynamics and the Deborah number.
"Disordered drug delivery" is an innovative approach to improving the performance of new chemical entities delivered to the human body. In this technique, the molecules of the drug and/or its delivery system are kinetically trapped in a high energy non-crystalline state. The resulting disordered or "amorphous" material offers potential increases in solubility and biological activity of many thousand fold compared with more conventional crystalline forms of the drug. Despite having a molecular level structure akin to that of liquids, amorphous materials have macroscopic properties that are typical of solids and thus they may be presented to the patient in the form of a convenient solid dosage form. Significant advances in the fundamental understanding of amorphous pharmaceutical materials in the past ten years have permitted major steps forward in the rational design of disordered drug delivery systems. Recognition of significant levels of molecular mobility in the glassy regime and an in-depth appreciation of molecular relaxation times and their distributions have enabled rapid progress to be made in this field. Needs for the future include analytical techniques that can elucidate the complex, dynamic and heterogeneous structure of amorphous materials and reliable models to predict the physical stability and in-vivo performance of disordered drug delivery systems. There are also significant opportunities for the production of disordered drug delivery systems with tailor-made properties through the careful engineering of custom amorphous alloys.
Hancock
Bruno C
BC
Pfizer Inc., Groton, CT 06340, USA. bruno_c_hancock@groton.pfizer.com
D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003460:Crystallization; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011205:Povidone; D012995:Solubility
D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D011205:Povidone; D007213:Indomethacin