Pharmaceutical applications of cyclodextrins: basic science and product development

Abstract

Objectives Drug pipelines are becoming increasingly difficult to formulate. This is punctuated by both retrospective and prospective analyses that show that while 40% of currently marketed drugs are poorly soluble based on the definition of the biopharmaceutical classification system (BCS), about 90% of drugs in development can be characterized as poorly soluble. Although a number of techniques have been suggested for increasing oral bioavailability and for enabling parenteral formulations, cyclodextrins have emerged as a productive approach. This short review is intended to provide both some basic science information as well as data on the ability to develop drugs in cyclodextrin-containing formulations. Key findings There are currently a number of marketed products that make use of these functional solubilizing excipients and new product introduction continues to demonstrate their high added value. The ability to predict whether cyclodextrins will be of benefit in creating a dosage form for a particular drug candidate requires a good working knowledge of the properties of cyclodextrins, their mechanism of solubilization and factors that contribute to, or detract from, the biopharmaceutical characteristics of the formed complexes. Summary We provide basic science information as well as data on the development of drugs in cyclodextrin-containing formulations. Cyclodextrins have emerged as an important tool in the formulator's armamentarium to improve apparent solubility and dissolution rate for poorly water-soluble drug candidates. The continued interest and productivity of these materials bode well for future application and their currency as excipients in research, development and drug product marketing.

Rapid quantification of 2-hydroxypropyl-β-cyclodextrin in liquid pharmaceutical formulations by 1H nuclear magnetic resonance spectroscopy

“…Among them, 2-hydroxypropyl-b-cyclodextrin (2-HP-b-CD) is found in several pharmaceutical formulations such as eye drops, oral solutions or I.V. solutions (Loftsson and Brewster, 2010). According to United States Pharmacopeia and European Pharmacopeia guidelines, the characterization and quantification methods of pharmaceutical excipients should be defined.…”

Thermodynamic Study of Grinding-Induced Loratadine Inclusion Complex Formation Using Thermal Analysis and Curve-Fitted FTIR Determination

“…The energetic input of solid-state grinding has been reported not only to alter the particle size, crystallinity, and solid-state polymorphic conversion of the drug but also to produce the drug-excipient interaction, resulting in the modification of physical and chemical properties of drug to finally influence the drug bioavailability Challa et al, 2005;Davis & Brewster, 2004;Loftsson & Brewster, 2010;Miller et al, 2007;Morris et al, 2001;Zhang et al, 2004).…”

“…Thus, CDs have been extensively applied to the pharmaceutical dosage form development for various drugs. Up-to-date, over 30 CDcontaining drug products have been commercialized on the global pharmaceutical market for clinical use (Davis & Brewster, 2004;Loftsson & Brewster, 2010).…”

Untitled

“…100 years after their discovery, with the development of new modified polymers and technologies cyclodextrins are still regarded as novel excipients of unexplored possibilities. [39,134] …”