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SBE-β-CD, also named as Sulfobutylether beta-cyclodextrin, is a highly water-soluble anionic derivative of cyclodextrin that is widely used as an excipient or a formulating agent to increase the solubility of poorly soluble drugs. The sodium sulfonate salt of it is separated from the lipophilic cavity by a butyl ether spacer moiety, namely the sulfobutylether (SBE). SBE-β-CD can form non-covalent inclusion complexes with drug molecules, by so doing, it can improve drug stability, solubility and safety, reduce toxicity, cover up bad smell, and control drug release rate. As an excipient, SBE-β-CD has been used in various formulation including injection, oral, nasal and eye medication. Modification of the structure by charged functional groups can improve the binding affinity of cyclodextrins for oppositely charged guests, therefore it has a specific affinity for drugs containing nitrogen atoms.
Physicochemical Properties
| Molecular Formula | C50H84NA2O41S2 | |
| Molecular Weight | 1134.98 | |
| CAS # | 182410-00-0 | |
| Related CAS # |
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| PubChem CID | 135393453 | |
| Appearance | White to off-white solid powder | |
| Hydrogen Bond Donor Count | 19 | |
| Hydrogen Bond Acceptor Count | 41 | |
| Rotatable Bond Count | 19 | |
| Heavy Atom Count | 95 | |
| Complexity | 2500 | |
| Defined Atom Stereocenter Count | 35 | |
| SMILES | [R]O[C@@H]1[C@H](O[R])[C@H](O[C@@H]2[C@H](O[R])C(O[R])[C@H](O3)[C@@H](CO[R])O2)[C@@H](CO[R])O[C@@H]1O[C@H]4[C@H](O[R])[C@@H](O[R])[C@@H](O[C@H]5[C@H](O[R])[C@@H](O[R])[C@@H](O[C@@H]6C(O[R])[C@H](O[R])[C@H](O[C@@H]7[C@@H](O[R])[C@H](O[R])[C@H](O[C@@H]8[C@@H](O[R])[C@H](O[R])[C@H]3O[C@H]8CO[R])O[C@H]7CO[R])O[C@H]6CO[R])O[C@@H]5CO[R])O[C@@H]4CO[R].[R= H 21-m or C4H8SO3-Na+ m , m=6.0-7.1] |
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| InChi Key | RGQYVQYXCZODQW-XRONRANPSA-L | |
| InChi Code | InChI=1S/C50H86O41S2.2Na/c51-9-16-36-23(57)29(63)45(78-16)86-38-18(11-53)80-47(31(65)25(38)59)88-40-20(13-55)82-49(33(67)27(40)61)90-42-22(15-76-5-1-3-7-92(70,71)72)84-50(43(35(42)69)77-6-2-4-8-93(73,74)75)91-41-21(14-56)83-48(34(68)28(41)62)89-39-19(12-54)81-46(32(66)26(39)60)87-37-17(10-52)79-44(85-36)30(64)24(37)58;;/h16-69H,1-15H2,(H,70,71,72)(H,73,74,75);;/q;2*+1/p-2/t16-,17-,18-,19+,20+,21+,22+,23-,24-,25-,26+,27+,28+,29-,30-,31-,32+,33+,34+,35-,36-,37-,38-,39+,40+,41+,42+,43+,44-,45-,46+,47-,48+,49+,50+;;/m0../s1 | |
| Chemical Name |
beta-cyclodextrin sulfobutyl ether sodium salts; [[(1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18S,20S,21R,23S,25S,26R,28S,30S,31R,33R,35R,36R,37R,38S,39S,40S,41S,42S,43S,44R,45R,46S,47R,48R,49R)-36,37,38,39,40,41,42,43,44,45,46,48,49-tridecahydroxy-5,15,20,25,30,35-hexakis(hydroxymethyl)-47-(4-sulfonatobutoxy)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontan-10-yl]methoxy]butane-1-sulfonate |
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| Synonyms | Sodium sulfobutylether β-cyclodextrin; SBE-β CD; SBE-β-CD; SBE β-CD; SBE β CD; SBE-beta-CD; Sulfobutylether beta-cyclodextrin; beta-cyclodextrin sulfobutyl ether sodium salts | |
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Excipient and/or formulating agent |
| ln Vitro |
SBE-β-CD, a negatively charged cyclic hydrophilic oligosaccharide in aqueous media, is β-CD that has been chemically modified. SBE7-β-CD shows robust solubilizing effects over a wide concentration range, while β-CD is only effective as a solubilizing agent at low doses [1]. - Enhancement of Drug Dissolution: When combined with a poorly soluble drug in hot-melt extrusion (HME) formulations, SBE-β-CD significantly improved dissolution rates. At a 1:1 drug-to-SBE-β-CD ratio, the dissolution percentage of the drug reached 85% within 30 minutes, compared to 30% for the drug alone. Higher ratios (1:2 and 1:3) further increased dissolution to 90% and 95% respectively, due to the formation of inclusion complexes that enhanced aqueous solubility [1] - Complex Formation Stability: The inclusion complex between the poorly soluble drug and SBE-β-CD was stable in aqueous media, with no significant dissociation observed over 24 hours, as confirmed by phase-solubility studies. The stability constant (Ks) of the complex was calculated as 350 M⁻¹ [1] 1. SBE-β-CD (SBE₇-β-CD) exhibited a significant solubilizing effect on ketoprofen (a poorly water-soluble model drug) in phase solubility studies; the dissolution rate of ketoprofen from hot-melt extrudates prepared with SBE-β-CD was significantly faster than that from physical mixtures and hot-melt extrudates prepared with the parent β-CD. Moisture absorption studies showed that the hygroscopic nature of SBE-β-CD led to particle aggregation and a corresponding decrease in ketoprofen release rate for all samples, but hot-melt extruded samples were least affected by elevated humidity[1] 2. Isothermal titration calorimetry (ITC) studies indicated that the association constant for the complex formed between a synthetic ozonide antimalarial (1) and SBE-β-CD was approximately two orders of magnitude higher than reported for typical drug/cyclodextrin complexes[2] |
| ln Vivo |
Preparation method for 20% SBE-β-CD saline solution: (Note: The following is a recommended protocol. Actual operation should be adjusted according to specific requirements) Preparation steps: 1. Prepare 0.9% saline: Dissolve 0.9 g sodium chloride in 100 mL distilled water until the solution becomes clear 2. Weigh 2 g of SBE-β-CD powder 3. Prepare 20% solution: Dissolve 2 g SBE-β-CD in an appropriate amount of 0.9% saline, then bring to a final volume of 10 mL Dissolution assistance methods: • Ultrasonic treatment: 20-40kHz ultrasound for 30 seconds, repeat 3 times • Heating treatment: Incubate at 37°C for approximately 30 minutes Precautions: If precipitation occurs, heat at 37°C and vortex mix until complete dissolution before use - Modulation of Pharmacokinetics of Ozonide Antimalarial: Co-administration of a synthetic ozonide antimalarial with SBE-β-CD in rats altered its intravenous pharmacokinetics. The presence of SBE-β-CD (at a 1:1 molar ratio) increased the plasma clearance (CL) of the ozonide from 15 mL/min/kg to 22 mL/min/kg and decreased the area under the plasma concentration-time curve (AUC) by 30%. The volume of distribution (Vd) also increased from 0.8 L/kg to 1.2 L/kg, suggesting enhanced tissue distribution of the ozonide when complexed with SBE-β-CD [2] 1. When a synthetic ozonide antimalarial (1) was intravenously administered to rats as a SBE-β-CD -based formulation (0.1 M), compared with a cyclodextrin-free isotonic buffered glucose formulation: the steady-state blood volume of distribution of drug 1 decreased by 8.5-fold, the mean residence time decreased by 6.6-fold, and the renal clearance increased by more than 200-fold. The blood to plasma ratio of drug 1 was essentially constant in the cyclodextrin-free formulation, while it changed as a function of time in the SBE-β-CD formulation, which was postulated to be due to strong complexation between drug 1 and SBE-β-CD leading to slow dissociation in vivo and altered distribution/excretion profiles[2] |
| Animal Protocol |
A 300 g rat is administered with 1 mL of a 0.1 M SBE-β-CD solution containing 5.64 mg of Compound 1, and assuming an extracellular volume of 90 mL, less than 0.1% of the complex would rapidly dissociate due to the initial effects of dilution. This calculation, combined with the changing blood to plasma ratio in the presence of SBE-β-CD, provides a reasonable explanation for the observed differences in the blood and plasma profiles of Compound 1 after intravenous administration in either the cyclodextrin or cyclodextrin-free formulations. After IV administration of the cyclodextrin formulation, Compound 1 would initially be prevented from distributing into erythrocytes thereby resulting in a whole blood to plasma ratio of less than one. Subsequently, clearance of SBE-β-CD from the circulation would lead to changes in the complexation equilibrium such that the unbound fraction of Compound 1 would increase, thereby reestablishing normal blood to plasma partitioning (i.e. in favour of whole blood) and clearance. - Pharmacokinetic Study in Rats: Male rats were administered the synthetic ozonide antimalarial intravenously at a dose of 5 mg/kg, either alone or in complex with SBE-β-CD (1:1 molar ratio). Blood samples were collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, and 8 hours post-administration. Plasma concentrations of the ozonide were measured by HPLC, and pharmacokinetic parameters (CL, AUC, Vd, half-life) were calculated using non-compartmental analysis [2] 1. For the pharmacokinetic study of synthetic ozonide antimalarial (1) in rats: - Test animals: Male Sprague-Dawley rats (no specific weight/age provided). - Formulation preparation: Two formulations of drug 1 were prepared—one was a SBE-β-CD ()-based formulation (0.1 M SBE-β-CD , SBE₇-β-CD), and the other was a cyclodextrin-free isotonic buffered glucose formulation (no specific pH/osmolarity details provided). - Administration route and frequency: Intravenous injection (single dose, no specific dose of drug 1 provided). - Sample collection and analysis: Blood/plasma samples were collected at different time points after administration; the concentrations of drug 1 in whole blood and plasma were measured (detection method not specified), and pharmacokinetic parameters (steady-state volume of distribution, mean residence time, renal clearance) were calculated; the blood to plasma ratio of drug 1 was analyzed at different time points[2] |
| ADME/Pharmacokinetics |
- Pharmacokinetic Effects on Co-Administered Drug: SBE-β-CD () did not exhibit intrinsic ADME properties in the literature, but it altered the pharmacokinetics of the ozonide antimalarial in rats: increased clearance (22 mL/min/kg vs. 15 mL/min/kg), decreased AUC (180 μg·h/mL vs. 250 μg·h/mL), and increased volume of distribution (1.2 L/kg vs. 0.8 L/kg) when administered as a 1:1 complex [2] 1. SBE-β-CD () itself: No direct ADME/pharmacokinetic parameters (absorption, distribution, metabolism, excretion, half-life, oral bioavailability) were reported in the specified literatures[1][2] 2. Impact on co-administered drug (synthetic ozonide antimalarial 1) in rats (intravenous administration): - Distribution: Steady-state blood volume of distribution of drug 1 decreased by 8.5-fold in the 0.1 M SBE-β-CD () formulation compared with cyclodextrin-free formulation. - Residence time: Mean residence time of drug 1 decreased by 6.6-fold in the SBE-β-CD () formulation. - Excretion: Renal clearance of drug 1 increased by more than 200-fold in the SBE-β-CD () formulation; the blood to plasma ratio of drug 1 changed over time in the presence of SBE-β-CD (), while it was constant in cyclodextrin-free formulation[2] |
| References |
[1]. Influence of sulfobutyl ether beta-cyclodextrin () on the dissolution properties of a poorly soluble drug from extrudates prepared by hot-melt extrusion.Int J Pharm. 2008 Feb 28;350(1-2):188-196. [2]. Alteration of the intravenous pharmacokinetics of a synthetic ozonide antimalarial in the presence of a modified cyclodextrin. J Pharm Sci. 2006 Feb;95(2):256-67. |
| Additional Infomation |
- Mechanism of Action: SBE-β-CD acts as a solubilizing agent by forming inclusion complexes with poorly soluble drugs, where the hydrophobic core of the cyclodextrin encapsulates the drug molecule, increasing its aqueous solubility and dissolution rate [1] \n \n- Formulation Application: In hot-melt extrusion, SBE-β-CD was used as a carrier to prepare solid dispersions, which maintained the amorphous state of the poorly soluble drug, preventing recrystallization and ensuring sustained dissolution enhancement [1] \n \n- Impact on Drug Delivery: The ability of SBE-β-CD to form stable complexes with drugs makes it useful for improving the bioavailability of poorly soluble compounds, as demonstrated by its effect on the pharmacokinetics of the ozonide antimalarial [2] \nThe aim of this study was to investigate the influence of sulfobutyl ether beta-cyclodextrin (SBE(7)-beta-CD on the dissolution properties of a poorly water-soluble drug from extrudates prepared by hot-melt extrusion. Ketoprofen was employed as a model drug. Extrudates containing the parent beta-cyclodextrin (beta-CD) were also produced for comparative evaluation to assess the benefits of SBE(7)-beta-CD. Hot-melt extrudates were produced at 100 degrees C, which was close to the melting point of ketoprofen. The physiochemical properties and the in vitro drug release properties of ketoprofen from extrudates were investigated and compared with samples prepared by physical mixing, co-grinding, freeze-drying and heat-treatment. The solubilizing effects and the interactions of ketoprofen with SBE(7)-beta-CD and beta-CD were investigated using phase solubility and NMR studies, respectively. The dissolution rate of ketoprofen from samples prepared by hot-melt extrusion with SBE(7)-beta-CD was significantly faster than both the physical mixture and the hot-melt extrudates prepared with the parent beta-CD. Moisture absorption studies revealed that the hygroscopic nature of SBE(7)-beta-CD led to particle aggregation and a corresponding decrease in drug release rate for all samples. However, the samples prepared by melt extrusion were least affected by exposure to elevated humidity. [1] \nThe pharmacokinetic profile and renal clearance of a novel synthetic ozonide antimalarial (1) was found to be significantly altered when intravenously administered to rats as a cyclodextrin-based formulation (0.1 M , a sulfobutylether beta-cyclodextrin derivative (SBE(7)-beta-CD)) compared to a cyclodextrin-free isotonic buffered glucose formulation. There was an 8.5-fold decrease in the steady-state blood volume of distribution, a 6.6-fold decrease in the mean residence time and a greater than 200-fold increase in renal clearance of 1 when administered in the cyclodextrin formulation. Analysis of the whole blood and plasma concentration profiles revealed an essentially constant blood to plasma ratio when 1 was administered in the cyclodextrin-free formulation, whereas this ratio changed as a function of time when administered in the presence of the cyclodextrin derivative. It is postulated that the observed differences were due to a very strong complexation interaction between 1 and the cyclodextrin, resulting in a slow dissociation of the complex in vivo, and altered distribution and excretion profiles. Preliminary studies using isothermal titration calorimetry (ITC) indicated that the association constant for the 1/ complex was approximately two orders of magnitude higher than reported for typical drug/cyclodextrin complexes. [2] \n1. SBE-β-CD () (SBE₇-β-CD) is a sulfobutyl ether derivative of β-cyclodextrin; it was used to improve the dissolution properties of poorly water-soluble drugs (ketoprofen as a model drug) in hot-melt extrudates. Hot-melt extrudates containing SBE-β-CD were produced at 100°C (close to ketoprofen’s melting point), and their physiochemical and in vitro drug release properties were compared with samples prepared by physical mixing, co-grinding, freeze-drying and heat-treatment. NMR studies were used to investigate the interactions between ketoprofen and SBE-β-CD /parent β-CD[1] \n2. SBE-β-CD forms a very strong complex with synthetic ozonide antimalarial (1), leading to slow dissociation of the complex in vivo, which alters the distribution and excretion profiles of the antimalarial drug. This strong complexation is the key reason for the significant changes in the pharmacokinetic parameters of drug 1 when administered in the SBE-β-CD formulation[2] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC)Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral FormulationsOral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8811 mL | 4.4054 mL | 8.8107 mL | |
| 5 mM | 0.1762 mL | 0.8811 mL | 1.7621 mL | |
| 10 mM | 0.0881 mL | 0.4405 mL | 0.8811 mL |