Curcumin, the main active ingredient found in turmeric (Curcuma longa), offers a wide range of beneficial pharmacological activities, including antioxidant, anti-inflammatory, and anti-cancer properties.However, its potential therapeutic benefits have been severely limited by its poor water solubility, which leads to very low oral bioavailability and rapid metabolism in the human body.Curcumin's hydrophobic nature causes its molecules to agglomerate in the body, resulting in minimal absorption in the gut, with most of it being excreted unabsorbed.Even when larger amounts of curcuminoids are provided through dietary supplements, ensuring adequate bioavailability remains a challenge.Traditional methods, like combining curcumin with piperine, have shown increased blood concentration, but this effect was short-lived, dropping quickly after only one hour.Why use cyclodextrin complexes?

Significantly Enhanced Bioavailability and Absorption: Cyclodextrins are naturally occurring oligosaccharides with a donut-shaped, three-dimensional structure featuring an inner hydrophobic cavity capable of encapsulating lipophilic molecules like curcumin. Their hydrophilic exterior ensures compatibility in aqueous systems, leading to molecular dispersions that greatly enhance curcumin's bioavailability. This allows a much larger number of curcumin molecules to be transported to the epithelial cell membrane in the upper intestinal tract for absorption.Human clinical studies have demonstrated that a cyclodextrin-based curcumin formulation was about 40 times more efficiently absorbed than pure curcumin extract and some leading commercial products.One clinical study found curcumin uptake to be at least 4.6 times higher than the next-best commercial curcumin formulation

This podcast episode is about the key application of cyclodextrins: solubility enhancement.

Cyclodextrins (CDs) are important functional excipients in pharmaceuticals, primarily recognized for their ability to solubilize poorly water-soluble drugs. They are cyclic oligosaccharides derived from starch, shaped like a truncated cone or torus. The exterior of the cone is hydrophilic, while its central cavity is relatively lipophilic, allowing it to interact with hydrophobic guest molecules.

Here's an overview of their solubilization properties:

• Mechanism of Solubilization: The most prominent mechanism involves the formation of non-covalent, dynamic inclusion complexes in solution, where a drug molecule (guest) enters the lipophilic cavity of the cyclodextrin (host). Beyond this, CDs can also contribute to solubilization through the formation of non-inclusion based complexes, the creation of aggregates and related domains, and their capacity to form and stabilize supersaturated drug solutions.
• Impact on Drug Properties:
• Types of Cyclodextrins Used: The most commonly used cyclodextrins for pharmaceutical applications are α-cyclodextrin (αCD), β-cyclodextrin (βCD), and γ-cyclodextrin (γCD), along with some of their derivatives. Derivatives like hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD) are particularly well-studied and have advanced to market.
• Complex Stoichiometry and Challenges: While a 1:1 drug/cyclodextrin complex (one drug molecule with one CD molecule) is the most common stoichiometry, it has become clear that solubilizing effects often involve the formation of multiple inclusion and non-inclusion complexes. For natural cyclodextrins, a tendency to coprecipitate with the drug can limit their use, although using combinations of different cyclodextrins can help overcome this issue, sometimes showing additive or even synergistic solubilizing effects.

These properties make cyclodextrins valuable tools in addressing the challenges of poorly water-soluble drug candidates in pharmaceutical development.

Unlocking Molecular Secrets: The Tricks of Making Cyclodextrin ComplexesEver wondered how to transform challenging compounds into powerful, effective solutions? Join us for the 7th episode of Carbohydrate Chronicles podcast where we delve into the fascinating world of cyclodextrins – these remarkable molecules with a unique truncated cone or donut shape and a hydrophobic cavity.Discover how they form inclusion complexes with a wide variety of molecules, dramatically increasing solubility, improving stability, enhancing wettability, and boosting bioavailability. Learn how these complexes can even mask undesirable properties like taste, smell, irritation, and toxicity.We'll uncover the critical importance of achieving true complexation and explore the diverse industrial techniques used to make these complexes on a large scale. From their traditional role as excipients to emerging novel applications in pharma and nutraceuticals, cyclodextrins are transforming product development across industries. Don't miss out on understanding these "friendly" molecules that can be incorporated into virtually any dosage form!