Amorphous drug delivery systems: molecular aspects, design, and performance.
The biopharmaceutical properties-especially the solubility and permeability-of a molecule contribute to its overall therapeutic efficacy. The newer tools of drug discovery have caused a shift in the properties of drug-like compounds, resulting in drugs with poor aqueous solubility and permeability, which offer delivery challenges, thus requiring considerable pharmaceutical manning. The modulation of solubility is a more viable option for enhancing bioavailability than permeability, because of the lack of "safe" approaches to enhance the latter. Solid-state manipulation in general, and amorphization in particular, are preferred ways of enhancing solubility and optimizing delivery of poorly soluble drugs. This review attempts to address the diverse issues pertaining to amorphous drug delivery systems. We discuss the various thermodynamic phenomenon such as glass transition, fragility, molecular mobility, devitrification kinetics, and molecular-level chemical interactions that contribute to the ease of formation, the solubility advantage, and the stability of amorphous drugs. The engineering of pharmaceutical alloys by solubilizing and stabilizing carriers, commonly termed solid dispersions, provide avenues for exploiting the benefits of amorphous systems. Carrier properties, mechanisms of drug release, and study of release kinetics help to improve the predictability of performance. The review also addresses the various barriers in the design of amorphous delivery systems, use of amorphous form in controlled release delivery systems, and their in vivo performance.
Kaushal
Aditya Mohan
AM
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
Gupta
Piyush
P
Bansal
Arvind Kumar
AK
D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D001682:Biological Availability; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D005898:Glass / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D010599:Pharmacokinetics; D044367:Phase Transition; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical; D013816:Thermodynamics
D000277:Adjuvants, Pharmaceutic; D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D011108:Polymers