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!

Step into the future of medicine and manufacturing, where a remarkable class of compounds called cyclodextrins (CDs) is transforming the landscape of 3D and 4D printing for critical biomedical and pharmaceutical applications.Imagine 3D printed objects that dynamically change shape in response to environmental cues like moisture or temperature – a concept known as 4D printing, vividly demonstrated by a shape-shifting flower with variable flexibility.These safe, sustainable, and highly versatile cyclodextrins enable homogeneous dispersion of challenging drugs in water-based mixtures, foster self-healing properties, and provide tunable architectures sensitive to a range of stimuli.Crucially, cyclodextrins are powering the shift towards personalized medicine, especially for pediatric patients, allowing for the Direct Powder Extrusion (DPE) 3D printing of customized dosage forms, like Mini-Tablets, that precisely deliver drugs such as budesonide with enhanced solubility and site-specific release to target conditions like eosinophilic colitis.Beyond printing, their applications extend to polymeric nanoparticles, one-dimensional nanostructures (nanofibers), and hydrogels for advanced drug delivery, tissue engineering, and wound healing, underscoring their profound impact on healthcare innovation.

Cyclodextrins are discussed in the sources as potential supplements for athletes, with information provided on two main types: Highly Branched Cyclic Dextrin (HBCD) and Alpha-cyclodextrin (αCD).

Highly Branched Cyclic Dextrin (HBCD), often referred to as Cluster Dextrin, is described as a complex carbohydrate derived from starch that has high digestibility and absorption rates, allowing for relatively quick bioavailability of D-glucose molecules in the bloodstream. It is noted for providing better gastric emptying processes and a favorable glycemic response compared to some other carbohydrate formulations. The properties of HBCD may be beneficial for athletes in high-intensity sports, such as weightlifting, by potentially providing faster glucose availability without significantly increasing insulin levels, and for athletes in long-duration exercises by potentially reducing gastrointestinal discomfort. However, a study investigating the effects of a 30g intake of cyclodextrin (Cluster Dextrin) during CrossFit® training did not find significant metabolic or performance effects in general CrossFit tests, although some differences were observed in specific tests like countermovement jump power. The data regarding performance improvements from this specific study were not conclusive, and further research is needed.

Alpha-cyclodextrin (αCD) is a different type of cyclodextrin, described as a cyclic hexasaccharide composed of six glucose units. Unlike HBCD, αCD is not digested in the human small intestine but is completely fermented by gut microbes. Studies in healthy, active non-athlete men have shown that supplementation with αCD significantly improved endurance exercise performance, specifically the 10 km biking time trial, compared to a placebo group. αCD supplementation was also associated with a significant reduction in post-exercise fatigue and a suppressed heart rate increase during exercise. The potential mechanism for these benefits may involve gut bacteria that ferment αCD to produce short-chain fatty acids like propionate, which could facilitate hepatic glucose production for energy during exercise. αCD is considered a safe substance and may serve as a supplement to support endurance exercise performance and reduce post-exercise fatigue.

Highlighting the difference between cyclic dextrin and cyclodextrin: While Highly Branched Cyclic Dextrin (often called Cluster Dextrin) is sometimes referred to as cyclodextrin, the sources note that it is a different molecule from alpha-cyclodextrin.

New Podcast Episode: Cyclodextrins in Food and Nutraceuticals
Unlock the hidden potential of cyclodextrins in your products!
From improving bioavailability to enhancing stability and masking off-flavors, cyclodextrins are revolutionizing the way we formulate food supplements and functional ingredients.

In this episode, we break down the science into practical insights and explore how these ring-shaped sugar molecules are making a real impact in health and nutrition.

Tune in now and discover why cyclodextrins might be your next formulation game-changer!

🎙️ Understanding Cyclodextrin Safety – Myths & Facts

Cyclodextrins play a crucial role in pharmaceuticals, improving drug solubility and stability. But how do they interact with the human body, and what do we really know about their safety? In this episode, we explore:

🔹 How dosage and route of administration impact cyclodextrin safety
🔹 Key findings on oral, nasal, dermal, ocular, and intravenous applications
🔹 Considerations for patients with kidney impairment and young children
🔹 Insights from toxicology studies – what’s known, what’s uncertain

Join us as we break down the science behind cyclodextrins, addressing both their benefits and safety concerns in a balanced discussion. Tune in for expert insights!

🎙️ New Episode Alert – Carbohydrate Chronicles, S2E2
In this episode of Carbohydrate Chronicles, we’re diving deep into the world of cyclodextrins (CDs) and their fascinating potential in biological drug formulations. From stabilizing delicate protein therapeutics to boosting vaccine efficacy and breaking new ground in gene therapy, CDs are proving to be far more than just sugar rings. We unpack how their unique structure allows for molecular encapsulation—enhancing solubility, stability, and delivery while minimizing side effects. Whether you're in drug development or just love cutting-edge biotech, this masterclass offers a fresh look at how CDs are redefining the biologics space.

We also explore real-world applications and challenges: Why haven't CD-based monoclonal antibodies reached the market yet? How do CDs stack up against polysorbates, and what makes them ideal cryoprotectants in vaccines? Plus, get a sneak peek at CarboHyde’s pioneering research into CD-based gene delivery systems that could rival lipid nanoparticles in efficiency and safety. Tune in to discover how these versatile molecules are quietly reshaping the future of pharmaceutical formulations.