What Is Cyclodextrin Phosphate Sodium Salt?
Cyclodextrin phosphate sodium salt is a water-soluble derivative of cyclodextrin, a cyclic oligosaccharide composed of α-(1→4)-linked glucose units. Its molecular backbone retains the toroidal architecture of native cyclodextrins—typically α-cyclodextrin phosphate sodium salt, β-cyclodextrin phosphate sodium salt, or γ-cyclodextrin phosphate sodium salt—while incorporating phosphate groups on the hydroxyl sites of the glucose monomers. These phosphate substitutions enhance aqueous solubility, modify the electrostatic profile, and improve the thermal and chemical stability of the parent compound. Among these, gamma-Cyclodextrin dihydrogen phosphate sodium salt, consisting of eight glucose units, is particularly noted for its spacious internal cavity and superior inclusion capabilities.
The external hydrophilic phosphate-modified rims allow the molecule to disperse efficiently in water, while the hydrophobic internal cavity retains its ability to form non-covalent inclusion complexes with poorly soluble guests, such as lipophilic drug molecules or volatile organic compounds. This amphiphilic nature renders the compound ideal for bioactive delivery and encapsulation technologies.
How Is Cyclodextrin Phosphate Sodium Salt Synthesized?
Cyclodextrin phosphate sodium salt can be prepared by direct phosphorylation of native cyclodextrin using a variety of phosphorylating agents including phosphorus pentoxide (P2O5), phosphorus oxychloride (POCl3) or dialkyl chlorophosphates. The reaction is typically carried out under mildly alkaline conditions, leading to selective phosphorylation of the hydroxyl groups present in the cyclodextrin molecule. The degree of substitution and the site of phosphorylation can be controlled to tailor the physicochemical properties of the resulting product.
Following phosphorylation, the product is neutralized using sodium hydroxide to form the corresponding sodium salt. This step increases the hydrophilicity and ionization of the molecule, leading to improved water dispersibility and suitability for formulation into pharmaceutical products.
What Are the Key Applications in Drug Delivery?
One of the most critical uses of cyclodextrin phosphate sodium salt is in drug delivery systems, where it serves as a solubilizing agent and complexation host. Through non-covalent encapsulation of hydrophobic drugs within its cavity, the compound dramatically improves the apparent solubility and bioavailability of poorly soluble active pharmaceutical ingredients (APIs). It also offers chemical stabilization by shielding labile drugs from hydrolysis, oxidation, or photodegradation.
The phosphate groups further introduce ionic character, which enhances mucoadhesion and can prolong drug retention at mucosal surfaces, a feature particularly advantageous in ocular, nasal, and buccal formulations. Additionally, this derivative is increasingly employed in the development of controlled-release systems, where the rate of drug liberation is fine-tuned by manipulating host–guest binding affinities.
How Is It Utilized in Food and Cosmetic Formulations?
In food applications, cyclodextrin phosphate sodium salt is used as a stabilizer, emulsifier, and encapsulation agent for flavors, vitamins, and other sensitive bioactives. It can solubilize lipophilic aroma compounds and prevent their premature evaporation or degradation during processing and storage. The presence of phosphate groups enhances its emulsification and dispersion properties, leading to improved homogeneity of food systems and potentially increased bioavailability of nutrients.
In cosmetic formulations, it can be employed to encapsulate fragrances, UV absorbers, and active ingredients in skincare and personal care products. It stabilizes sensitive ingredients and can improve the texture and sensory attributes of formulations, allowing for smoother application and controlled release on the skin.
How Does Cyclodextrin Phosphate Sodium Salt Compare to Other Cyclodextrin Derivatives?
We get requests for the sulfated, carboxymethylated, and hydroxypropylated versions of cyclodextrins all the time. So what's the benefit of using a phosphate-substituted cyclodextrin instead? Let's break it down:
| Property | Phosphate Derivative | Other Derivatives (e.g., HP-β-CD, SBE-β-CD) |
| Aqueous Solubility | High | Moderate to High |
| Ionic Character | Strong (anionic) | Variable (non-ionic to anionic) |
| Mucoadhesive Potential | Enhanced | Moderate |
| Complexation Efficiency | Superior (due to electrostatic interactions) | High |
| Regulatory Approval (food, pharma use) | Subject to region-specific constraints | Some are GRAS (e.g., HP-β-CD) |
Compared to sulfobutyl ether-β-cyclodextrin (SBE-β-CD), which is often used for injectable formulations, phosphate derivatives offer higher complexation affinity and ionic compatibility, making them more effective for targeted and site-specific delivery systems. Alfa Chemistry provides formulators with comparative consultation services to help find the best cyclodextrin variation for their application.
What Are the Safety and Regulatory Considerations?
Cyclodextrin Phosphate Sodium Salt is generally regarded as safe when used within recommended concentrations. However, its anionic nature may lead to ionic interactions with co-formulated APIs, excipients, or delivery system components, necessitating compatibility assessments during formulation development.
Extensively employed in R&D and industrial applications, its regulatory status for use in food/pharmaceuticals may depend on the extent of phosphorylation, administration route and target market. Users are advised to refer Safety Data Sheets (SDS) and local regulatory databases (e.g., FDA, EFSA, JP compliant listing) before commercial use.