Science topic

Cyclodextrins - Science topic

A homologous group of cyclic GLUCANS consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances.
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Dear all,
I use the kneading method in order to encapsulate silicon phthalocyanine dichloride in cyclodextrins (β-CD, γ-CD, HP-β-CD and Me-β-CD). My last calculations gave me encapsulation efficiency greater than 100%. Something went wrong... The protocol I follow is: Add i.e 5 mg of the dry complex of the cyclodextrin to 5 mL of DMF. The system is left under stirring for at least 24 hours. The solution is then filtered and fluorescence is measured.
Has anybody ever had a problem like this before and how did you overcome? How can I separate cyclodextrin complexes from the not encapsulated drug? I tried centrifugation without result.
Thank you!!
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Hi Eleni,
0. The complexation itself can enhance the fluorescence (see, e.g., doi:10.1016/j.jpba.2014.02.022, 10.1080/02652030701564555 )
1. It is a common mistake to assume that all the guest molecules form complexes upon kneading the components in a 1:1 molar ratio. More specifically, it is rare that equal molar ratio treatment results in complete complexation. That means the removal of uncomplexed guests is crucial. For the removal, one needs to use a solvent that is not a good guest for CD, does not dissolve the complex or the CD, and does not decompose the guest.
The silicon phthalocyanine dichloride content is an approximate value (~85%, according to, e.g., a known fine chemical supplier), you have to check the CofA for the measured value because the label contains the specification and not the measured value.
If some hydrolysis occurred before the complexation experiments, the content could be higher than expected. 2xOH~1Cl => ~5% more phthalocyanine content.
Because it is a reactive substance, it is difficult to find a suitable solvent. Maybe CH2Cl2, CHCl3 (be careful, CHCl3 always contains EtOH!), CCl4, DiPE, MTBE, or di-t-butyl ether?
2. The randomly substituted versions (HPbCD, RAMEB) suffer many systematic errors.
2.1 If the DS (Degree of Substitution) is a substituent/glucopyranoside unit, the calculation error of MW of the CD derivative is high. If the DS is in traditional terms (as the pharmacopeias define, number of substituent/CD), the MW calculation might be better. It is recommended to record 1H-NMR (D2O is a good choice because, in DMSO, the water overlaps with the methyl /RAMEB/ or methylene /HPbCD/ signals) and calculate yourself. Both ways give average values, but the calculation errors are different.
2.2 An additional problem is the water content of both HPbCD (2-5%) and RAMEB (0.5-1%). Measure the water content by drying (covered with paper, 90-100 oC, vacuum, in the presence of KOH/P2O5, overnight). It is recommended for the bCD (14% water), too. The freshly dried bCD or HPbCD adsorbs water quickly.
2.3 Because these data are rounded values, the calculation errors might significantly affect the weighing.
3. Did you record the fluorescence of untreated and similarly treated (with the complex preparation) guests? Is there a difference between the fluorescence spectra of dichloride, monochloride, and dihydroxy silicone phthalocyanine?
4. Because of the reactivity of the guest, the CD substitution cannot be excluded, though it is less probable. Either the multisubstitution of a CD or connecting two CDs can change the fluorescence signal strength. So can the single or double Cl=>OH exchange.
Good luck,
Laszlo
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are Cyclodextrins promising prebiotic agents ?
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Hello,
I am investigating interactions of poorly soluble pharmaceutical (nabumetone) with cyclodextrins in solution and solid-state. Complexes of nabumetone and beta cyclodextrins were prepared in different molar ratios by grinding in high-energy vibrational mills and corresponding physical mixtures were prepared using a mortar and the pestle as well (n:n = 5;1, 3:1, 2:1, 1:1, 1:2, 1:3 and 1:5). In the ATR spectra of ground samples with higher content of the pharmaceutical, I noticed an increase in the intensity of characteristic bands of the pharmaceutical (in comparison to corresponding spectra of physical mixture) but I didn't observe the same phenomena in the corresponding transmission spectra. Usually when these kinds of samples are investigated by infrared spectroscopy decrease in the intensity of the characteristic bands of the guest molecule is explained by the inclusion of the molecule in the hydrophobic cavity of cyclodextrin. What is the possible cause of these increments in nabumetone band intensities in ATR spectra? Why aren't these increments visible in transmission spectra as well?
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According to the sucrose experiment I did today, see Figure 3 (because I don't have your sample) (g-grind p-pressure), I think the enhanced spectrum after grinding in your experiment is that grinding increases the contact area between the sample and internal reflection element.
In the meantime, please give me feedback if you experiment on the Diamond-ATR, I'd love to know what's going on, thanks!
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Hi all,
I'm trying to separate Alpha, Beta and Gamma cyclodextrins from each other in a mixed aqueous solution. Now I know that there are slight differences in polarity of the different cyclodextrin molecules so my idea was to try and separate them using SPE.
The components have excellent separation on a silver-ion HPLC column, which suggests to me that SPE could work.
However after a few attempts I have noticed that the CDs have barely any retention on the SPE column.
I would love any suggestions on how to improve separation :)
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I am trying to tosylate cyclodextrin using the aqueous methods (water and NaOH). But they are not working. Does anybody prefer using organic solvents for this reaction?
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Dear Debasmita Paul many thanks for sharing this very interesting technical question with the RG community. If you have problems with the synthetic method using tosyl chloride, you might want to try the following alternative two-step synthesis in which the readily accessible 1-(p-tosyl)-imidazole is used as tosylating agent. The protocol has been described in great detail and is easy to follow::
Synthesis of mono-6-tosyl-β-cyclodextrin, a key intermediate for the functional cyclodextrin derivatives
Good luck with your experiments and best wishes, Frank Edelmann
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I am using C-18 column for my analysis. I noticed that after injecting some of my samples which contain cyclodextrins and drug, the back pressure increase. Even after I wash with mobile phase, 80% MeOH, 80% Water and 50:50 MeOH:Water for the whole day.
May I know is there any solutions for this problem?
Thank you.
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Dear Shi
Through our work experience, we have found that there is a way to overcome this problem and we tried this in our laboratory.
at first, you should wash your column with hot HPLC grade water 70 ceslius degree and let it move at flow rate 1 ml per minute for at least one hour, then you wash with methanol 50% for at least 30 minutes and finally, you wash with methanol 95% or 100% for at least 30 minutes
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Before trying different approaches I want to ask the experts in here!
- Is it necessary a supersaturated solution of β-CD? In the literature the amount of β-cyclodextrin always exceeds its solubility. Why?
- Are cyclodextrins able to form host-guest complexes with hydrophilic molecules? Or just hydrophobic molecules?
- Will the precipitate be crystalline and visibly colored? how should the precipitate be washed?
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May be this paper is useful about the use of non-saturated solutions of β-CD to remove dyes:
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Hi all,
we have a material containing cyclodextrins and cellulose-derived compounds linked with a crosslinker. All components of the polymer contain the same functional groups (such as OH, COOH). The material is insoluble in water and organic solvents. How can I check the degree of cross-linking and the way the how the components are linked with each other? I will be grateful for any suggestions.
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I suggest the following paper
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Solubilisers in injectables (USFDA approved)
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You could try Povidone (polyvinylpyrrolidone) K-30 or lower, in a concentration lower than 5%
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Hello.
I have some samples with cyclodextrins (beta-CD and its derivatives), and I noticed increase in back pressure of HPLC column (C18 column) after each run. Since the samples consist only of drug and cyclodextrin I concluded that the cyclodextrins are the cause.
So, I wonder if you have any suggestion how to wash them out of column.
I tried backflushing it with high water content but it doesn't help much. I also found an article that had similar problem, where they found that backflushing with phosphate buffer and MeOH (90:10) helps, but that was only for sulphobutyleter-B-cyclodextrin. Since I am working with other cyclodextrins I am wondering if anybody else had similar issue and how did you solve it?
Note: after each sequence run I flush my column with 80% water for an hour, and after that with 90% acetonitrile. That helps a little but the pressure still increases slightly.
Thank you in advance.
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Yes, we filter samples as well as dilute them and I am also using guard column. But thank you for your advice :)
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I am working with 3 different types of cyclodextrins and forming complex with lidocaine. I want to determine the association constant and dissociation constant of the cyclodextrin-lidocaine complex by HPLC method. Any direct references or similar work recommendations to follow/read would be highly helpful. Thanks
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I build a complex of cyclodextrin / perfume for use in detergent powder.
How Do I Know  perfume (guest molecule) have Appropriate characteristics for complexation with ß-cyclodextrin?
How Do I Know the guest really included in the ß-cyclodextrin cavity?
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Hello Ella fa ,
To enter the inner cavity of the beta-CDs your guest molecule needs to be quite apolar, but also it needs to match the size/dimensions of the inner cavity (for beta the diameter is around 0.6-0.65 nm).
As Laszlo Jicsinszky stated above, NMR is quite useful especially 2D NMR which allows you to observe interaction within the cavity.
You can also check my technical report where a lot of characterization techniques were used to study cyclodextrins : NMR, XRD, IR, UV, Liquid chromatography, SEM, TGA and TGA coupled with MS.
If you have any further questions do not hesitate to contact me.
Best regards,
Marie B.
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Hello to everyone! I need to solubilize an hydrophobic molecule whose diameter (approximately 11 Å) is slightly larger than the one of gamma cyclodextrin, do you know any other host molecule that can be suitable for the purpose or any lab/seller that can supply delta or epsilon cyclodextrins? Micelles and liposomes are not suitable for my purposes.
Thank you very much!
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The link provided by Andrei Rogoza is very useful.
If you are comparing alpha, beta and gamma-CDs: gamma-CDs are the largest ones; i.e., their cavity is "larger".
This is important to note that functionnalization of CDs may affect the aperture of the inner cavity (shrinking or expanding). Furthermore, the solvent also plays an important role in this effect.
Best regards,
Marie Berthuel.
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I am not an expert in that field so please help me to do it properly. I would like to obtain cationic beta-cyclodextrin in order to modify zeolite surface. I do not have acces to the particular literature reports unfortunatelly. What chemicals should I use ( I have found some amine derivatives) and how to do this? - I need practical tips.
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See attachment for the synthesis of the simplest cationic Beta-CD (CDNH3Cl)
Or conversion of the tosyl_CD with amines.
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The work reported by Enrico Redenti and Laura Ribeiro states that hydroxy acid increases the complexation efficiency of beta-cyclodextrin. They have prepared ternary (Drug/CD/Hydroxy acid) and quaternary (Drug/CD/Hydroxyacid/Hydrophilic polymer) inclusion complexes and found promising dissolution results. However, it is unclear that how much amount of hydroxy acid must be used for preparing this complex. There are some reports where the authors have used drug, CD and hydroxy acid in the molar ratio 1:1:0.5, whereas some have used 1: 1:1. But, on what basis this has been decided is still an unanswered question for me. Increasing the amount of citric acid will ionize the drug (off course the above mentioned complexes are related to the poorly soluble weak bases) and consequently dissolve it. The phase solubility study and Jobs plot help us to decide the molar ratio of drug and CD. I want to know that how to decide the number of moles of hydroxy acid (e.g. citric acid) that will be required for preparation of a ternary complex if we are preparing drug:CD complex in 1:1 molar ratio.
Ref:
1. Redenti et al. Drug/cyclodextrin/hydroxy acid multicomponent systems. Properties and pharmaceutical applications. J. Pharm. Sci. Vol. 89, 1–8 (2000).
2. Ribeiro et al. Multicomponent complex formation between vinpocetine, cyclodextrins, tartaric acid and water-soluble polymers monitored by NMR and solubility studies. European Journal of Pharmaceutical Sciences Vol. 24, 1–13 (2005).
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Thank you Dr. Santos.
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Hi there,
I am currently working on the inclusion complexation of ochratoxin A with several cyclodextrins derivatives. To find out which cyclodextrin has the highest inclusion efficiency, I plan to do a phase solubility study for all inclusion complexes. The thing is I have dissolved all of my ochratoxin A sample into organic solvent to prepare a stock, and dilute it multiple times before use. This is because ochratoxin A is quite expensive, and we cannot afford to put milligrams of it to run a single analysis. I just realised that phase solubility is only applicable to solid samples, so I guess my aqueous solution of ochratoxin A cannot be worked? If that’s the case, any other analysis that I can use to investigate the inclusion efficiency of diffferent cyclodextrins to encapsulate ochratoxin A?
Hope I made myself clear.
Much appreciated for any suggestions.
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Use Job plots for stoichiometry; the UV/vis titration requires low concentrations of components.
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Dear formulation experts,
We are facing a challenge when dosing the compound into the eye as eye-drops, aiming at the systemic exposure. Dosed compound caused mild irriation, and we are looking the ways to minimize that. Increasing the viscosity seems to work, but not enough. Also cyclodextrines are planned to be tested. Any insight and potential ideas related to composition or formulation technology to mask compound eye irritation will be highly appreciated.
Thank you for your time and effort!
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Try to adjust the pH of formulation near the pH of tear fluid.
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As we know, Cyclodextrins are cyclic hexamer, heptamer and octamer of α-D-glucose having 6, 7 & 8 numbers of glucopyranose units respectively bound by α-(1–4) linkages. Though, There is no terminal 1-4 linkage as they are cyclic....
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Check these out:
doi: 10.1007/BF00136475
doi: 10.1002/bio.292
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as you know, cyclodextrins have a 3 reactive alcohols. 2-OH, 3-OH and 6-OH, I am gonna to bind 2 molecules to them. what should i do?
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Although it is true that in esterification the O(6) is usually more active but, depending on the size of the molecule the O(3) can be also reactive. The steric hindrance of O(3) is more expressed when the ionization of the OH groups are needed - of course, bulky substituents, like Tr cannot react -, AND the O(2) is substituted. Another example is the tosylation of CDs in pyridine with TsCl. If you want to prepare mono-6-OTs, you need to do some preliminary experiments to find an optimal conditions for the max. yield of 6-OTs because O(2) and O(3) is also tosylated upon longer (>1 h) reaction.
If you have O(2) protected CD which is relatively stable (i.e. not TBDMS and the like or ester appended) and you want to esterify with a liquid anhydride then I would recommend the use of FeCl3*6H2O as (Lewis acid) catalyst. Usually 0.3-1.0 molar excess of anhydride/OH is enough
In case of Ac2O and FeCl3 the O(3) acylation is so fast that partial esterification not, only peracetylation could be achieved.
This method can be used also for even the butyrylation of per-2,6-dipentylation cyclodextrins.
The only drawback of the method is that - particularly when alkylated CDs are the subject of reaction - the opening of the macrocycle.To suppress the Lewis acid catalyzed glycolysis the parent acid (and lower than r.t.) can be used. For example in the mentioned butyrylation you need to cool the reaction mixture below 20 oC, use 1:1 mixture of butyric acid and butyric anhydride, and "spoonwise" addition of the CD; stop the reaction after 10 min otherwise a considerable part of the macrocycle opens (no inprocess control is possible). Or, in the per 3-O acylation of DIMEB requires some tricks, otherwise the very efficient synthesis of 2,6-di-O-methyl-1,3,4-triacetyl-Glcp is realized :) in a minute. The longer reaction times and/or higher (uncontrolled) temperature opens the pyranose ring.
Of course if there is/are another ester groups on the CD they are usually exchanged.
The method is also working with (liquid) acid chlorides but you need to remove the formed HCl e.g. with N2 or Ar. Per-3-O-palmitoyl-DIMEB can be prepared by this was, too.
If you need more details, contact me.
Good luck,
Laszlo
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We tried freeze drying, solvent evaporation and kneading methods but didn't get substantial XRD patterns of comlexes. 
In some articles, it was stated that the mixture was filtered before freeze-drying. But will filtration not cause material loss?
Some of the molecule is complexed with cyclodextrins, remeaning part of the drug gives the crystalline peak in XRD. Do you have a suggestion to increase the interaction between niclosamide and cyclodextrin?
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Hi Ozlem,
The XRD is not enough to very/confirm the complex formation. Of course, the presence of the crystalline guest suggests that the mixture contains considerable amount of the guest. Nothing else.
NMR is better: starting materials, products in D2O, or, it is better in 4:1 (or higher ratio) H2O:D2O. It depends on the NMR equipment you can access.
Yes, the solids removed before freeze-drying results is lower guest content, but -although the dissolved material is not necessarily fully complexed (please, note that is an equilibrium) - the solid is surely not complexed (or insoluble complex formed and precipitated but we can assume that not too much insolubles are there, and if the publications mention filtration it is suspicious that the insoluble is the guest only).
In order to verify the situation you can make the following simple experiment: Dissolve the solid from freeze drying of the clear (filtered) solution in water as much concentrated as you can achieve and dilute it simply with water. Usually, because in that case the dilution shifts the equilibrium the poorly soluble guest can be precipitated, or at least results in a hazy solution. Unfortunately, the lack of haziness/precipitation does not confirm the complexation.
The question is what your purpose is: soluble complex or preparation the highest guest:CD ratio?
If your aim is to prepare a soluble complex then the freeze drying of a clear solution is suitable, because there are good chances to redissolve the obtained solid.
If you want to prepare a composition with the highest ratio then kneading/ball milling is the suitable method. The only problem is that you will have uncomplexed guest also and the ratio of complexed/uncomplexed guest cannot be estimated a priori. And the removal of non-complexed guest is not solved.
And Gilles is right, recording the solubility isotherm helps, but that is an aid only not the solution.
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We observed decreased  sensitivity of our LCMS measurement data of plasma samples after analysing cyclodextrins.
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I fully agree to Marcos point. I do clean the capillary regulary which works quite ok but I always have a spare one that I can use if the cleaning was not giving me the sensitivity back which might be the case after 3-5 times cleaning.
In addition you might consider using the valve in the QQQ to switch to waste at the beginning to avoid the very polar matrix components going into the source. You can realize that is adding a time segment with the valve setting to waste. Using this I have a good experience in prolonged performance but also less stress on the chromatography column and longer stable results.
Hope this helps
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Hi
is it possible interaction between hydoxyl (OH) group of Cyclodextrins and Amine (NH2) and Amide group of other materials at 130 C temperature (High Temperature condition)?
solution pH : Alkaline (10-11) ,aqueous
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 The primary question is not absolutely clear: what reaction do you think between an OH group and an amino NH2 group? And which cyclodextrin with what kind of amines/amides?
 Joseph has right in the H-bonding but at the mentioned pH it has only very particular role. It is also true that the OH group is stable under alkaline conditions if the stability means chemical stability. 
 However, the pKa values of the secondary hydroxyls are relatively low, around 12, that means in the presence of an appropriate ionizing agent the OH groups can react - of course the N is more nucleophilic. There is no noticeable O-reaction until pH ~10.5.
 Regarding the amides, they like to go into the CD-cavity (but size matters). If you want to make reaction in DMF the complete removal of the residual (complexed) DMF is very difficult and usually Soxhlet extraction is needed. It is a problem only, of course,  if your last reaction is done in DMF. Generally acetamide forms less stable complexes. In basic conditions (>11) the CD may accelerate the hydrolysis but that is compound dependent.
 Lack of strong complexing moieties the amide group, including the carbonyl, is in the cavity, close to the secondary hydroxyl rim.
 If you have seen coloration (colorless->yellow->red->brown during the reaction) under the described conditions that means your cyclodextrin contains linear oligosaccharides as impurities. It is normal, all commercial naked CD contains that impurity. The amount of those reducing sugars are rather low (0.05-0.2 %) but due to the reducing sugars the strong base together with the high temperature results in uncontrollable side-reactions - like Canizzaro, disproportionation, or beta elimination. From the color aspect the last one is the most important. The beta-elimination, starting from the reducing end -  results in a double bond what is able to wander resulting in multiple unsaturated compounds which gave the color. The very good news is that although the the color is intensive but the amount of the unsaturated impurities is very low and easy to remove it by 2.5-10 % active carbon (charcoal). Of course in neutral (pH 5.5-7) or slightly acidic conditions (pH >3.5) are needed otherwise the carbon has lower adsorbing power. You can use lower pH but before solidification of solvent removal you need to go to up to 5.5-6.0 because in solid form the lower pH may cause decomposition of the macrocycle,
Good luck!
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how can I load ciprofloxacin on fabric which modified with betacyclodextrin? I mean what is condition (Temp. , pH, Time etc.) ?
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thanks Mr. Jicsinszky
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Dear Researchers,
I am looking to encapsulate some plant extracts in cyclodextrins, but I am unable to decide either water or ethanol based extracts or essential oils of particular plant will be more suitable. And, if possible, could anyone clarify the difference in extract and essential oil.
Thanks in advance.
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encapsulation using cyclodextrins is based on the fact that, the inner part of the ring is hydrophobic, which means that whatever you are trying to encapsulate should be hydrophobic as well as the carrier. 
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Is there any commercial pharmaceutical product(s) developed using Solid dispersion technology with Cyclodextrins?
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In order to facilitate the skin permeation of transdermal film of sodium hyaluronate , what possible strategies can be put into practice? Apart from using the permeation enhancer like cyclodextrins, any other changes in polymer selection or choosing particular solvent system or modification in film preparation by solvent casting method can be done? Thank you.
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Hi Sandeep Karki, a lot of penetration enhancers are available for topical drug delivery including fixed oils and volatile oils. I think the problem is sodium hyaluronate itself. It has high molecular weight and is water soluble, both of which limit penetration through skin.
As described by Rafik Karaman, you may need to use ethosomes (modification of liposomes) or chemically modify it for receptor mediated delivery. Although both ethosomes and conjugates can be loaded in thin films, I am not sure if you are ready to adopt these systems at this stage.
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ε = AF −A0/S0. (doi:10.1016/j.jpba.2008.02.018)
AF being the absorbance value of drug when is complexed
the presence of cyclodextrin showed that there was decreased in extinction coefficient of the drug. is it true? if yes , so A0 > AF? and extinction coefficient(ε) would be negative?
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Hi Fatemeh,
Rafik has partially right only. It is true that complexation with CDs has very poor effect on the absorption coefficient but the complexation usually causes the shifts of the maximum, i.e. as it is very often happens the extinction decreases because the maximum is shifted with some nm-s (either hypso- or bathochromic effect may occur). The so called Benesi-Hildebrand equation (which has been commonly used for many years to calculate the apparent 1:1 stability constant; Benesi H, Hildebrand J, A Spectrophotometric Investigation of the Interaction of Iodine with Aromatic Hydrocarbons. J. Am. Chem. Soc., 1949, 71(8): 2703–07). By the way, the calculation of the stability constant by the NMR shift changes is also based on similar phenomenon (but the chemical shifts changes).
 As a technical advice, if you want to use the UV, use 50 % aq. EtOH to decompose the complex (this is a "magic" mixture because it decomposes the majority of complexes) and then you can get the absorption maximum on the same nm as without CD. Of course you need to record the calibration curve in identical solvent mixture. If you are using (2-hydroxy)propyl-bCD (HPbCD) you should not have considerable absorption roughly over 230-240 nm - of course if your HPbCD is from a trusted source. Alternatively, you may add HPbCD to the blank solution with the same concentration as in the sample for UV but many times this is so complicated and has not too much advantages but brings new errors. Usually the couple of percent errors by the possible CD absorption does not matter. Additionally, please, also note the meaning of the absorption below e.g. 0.1 unit (I mean the absolute unit, not the difference) and the absorption range where the Lambert-Beer law is valid. Please, also consider what is the real meaning of the difference between e.g 1.8 mg/ml and 2.0 mg/ml solubility of your drug assuming 5 % experimental error. Your experimental error might be larger, because of the protocol used in the isotherm recording, like equilibration time, equilibration temperature, etc. Otherwise, a practical point of view, the calculation of the molar extinction coefficient is not very important, except if you want it to write into a publication. If you want to repeat the experiments later or with other CDs, it is better to re-record the calibration curve - or at least verify the previously recorded one.
 Please, also take into consideration that the apparent stability constants calculated from the solubility isotherms may have unreasonably high error when the base solubility of the guest is very low (because it is in the denominator) and the very low base solubility is difficult to determine. So, you should also use a "blank" experiment - without CD -, instead of the use of literature value(s).
 I would recommend to you two volumes of the Comprehensive Supramolecular Chemistry (Elsevier, Electronic ISBN 9780080912547), one is dealing with only with cyclodextrins (vol. 3) including all methods to calculate the complex stability constants - although this series is ~20 years old but not too much changes have been occurred in methods only the techniques have become more sophisticated. teh another volume is dealing with the most common physicochemical methods of supramolecular interactions (vol. 8). Of course, there are some other new books about it but these volumes contain the most comprehensive knowledge. 
There is a shortcut to avoid too much science :)  Higuchi T, Connors, KA, Phase-solubility techniques. Adv. Anal. Chem. Instrum. 4, 117-212, 1965.
 Good luck,
Laszlo
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Could not find enough information about cyclodextrine interaction with cholesterol. What are the concentrations and ratio of the components?
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I'm theoretical chemist. The idea behind is to enhance publications for both. I´d like to find experimentalists or theoretical researchers on this topic.
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I will be happy to assist. Please tell me what do you have in mind? 
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Can anyone give me a step-by-step Autodock tutorial to small molecule dock antioxidant to cyclodextrins?
Do you know how to dock antioxidant to cyclodextrins?
Can you give me a step-by-step tutorial?
I want to dock small molecule and antioxidant to cyclodextrins?
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A method to add small molecules to cyclodextrins is to solve the cyclodextrin in DMSO and to add maleic anhydride at 80-100°C. The maleic anhydride adds to the hydroxy groups of the cyclodextrin under formation of acidic half-ester
CYCLODEXTRIN-O-CO-CH=CH2-COOH
Now thiols (mercaptanes) can be added to the double bond wherein a thioether is formed (radical starters like AIBN support addition, 60-80°C)
CYCLODEXTRIN-O-CO-CH(SR)-CH2-COOH
As mercaptane e.g. cystein, mercaptopropionic acid, thiosalicyclic acid, mercaptophenol.... can be used. The thioethers have antioxidant properties.
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Dear colleagues,
In the literature there are several reports of crosslinking poly- or even oligosaccharides as cyclodextrins with sodium trimetaphosphate under relatively mild conditions (50-70 deg C, few hours) in the presence of sodium hydroxide. I tried to reproduce some of these papers using methlycellulose, an easily available, water soluble polysaccharide. I observed an unexpected phenomenon: the system gelled at 60 deg C but became a viscous fluid again after cooling back to room temperature. The same can be observed using simple methycellulose solution without STMP and sodium hydroxide. I could not find an easy explanation for this phenomenon. Especially the latter. (It may have happened that the crossliniking reaction itself was not completed or in a reversible way).
I would appreciate the comments of colleagues having practical experience in STMP crosslinking.
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Dear György,
I tried this method with some modification (http://onlinelibrary.wiley.com/doi/10.1002/1521-379X%28200006%2952:4%3C095::AID-STAR95%3E3.0.CO;2-X/epdf) many-many years ago and it worked - not completely as described, because I had a different oligosaccharide, but worked..
Alternatively, you may try P2O5 and MeCell in DMF at 50-90 oC then careful dilution with water and neutralization to pH 6.2-6.8 and dialysis, finally freeze drying. For the dialysis it is recommended to monitor both the in- and outside conductivity.
 The only problem might be that methylation of cellulose may block the most reactive hydroxyls and so the remained hydroxyls are not enough reactive either by steric hindrances or because of their inherent less reactivity.
Good luck
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As it illustrated in the attached picture, how to crosslink or polymerize Sulfonated butyl-cyclodextrins by -OH groups at small side?
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Hi Huslen,
 I am afraid that if your pic refers to the real location of the substituents (primary side up and secondary down and only one sulfobutyl gropu/CD ring) than the work is very long and complicated. First you need to prepare the mono-6-O-sulfobutylated (SB) CD then crosslink so that each CD is attached not more than 2 other CDs. It is complicated but not impossible. A possible way is that after the preparation of the mono-6-O-sulfobutylated CD - this is not easy, see later -, then 2(3)-O-monoallylation, then protect the hydroxyls (TMS?), epoxydation and deprotection. The epoxy will react practically exclusively with another secondary O under basic conditions perhaps in water (I suspect that the SB-epoxypropyl CD is soluble in water). If you are a fortunate guy, you can find appropriate conditions to get the structure on the pic. However, the preparation of 6-monoSB is a challenging task, because you need to protect all the hydroxyls except one O6 and then this OH can be reacted with butanesultone under basic conditions. Of course, there are some publications dealing with the site selective alkylations (look for e.g. Jindrich et al.) but in those cases the separation of the regional isomers are also difficult, additionally the butanesultone is very reactive and not only substitution but its hydrolysis and other side reactions with the solvent impurities might occur. My opinion that under the described alkylation conditions the O2 substitution would be the most dominant.
 If you have the sulfobutylated CD yet (commercially available SBCD), in that case you cannot do anything, because the SB is located practically only on the secondary rim, mainly on O2 and only a few of them is on the primary. In case of cyclodextrins, in the dominant cases of alkylation reactions, the O2 is the most reactive and not the primary one. O3 is usually poorly reactive, due to steric reasons, particularly when the vicinal O2 is substituted (and vice versa, but considerably less extent). In this case you can use epichlorohydrin or diepoxybutane for crosslinking using NaOH or KOH in water. Unfortunately, you will get a complex structure which is surely far from the targeted "linear" polymer and additionally, the crosslinking can occur on all free hydroxyls, not only on the primary ones and you will find dihydroxyalkyl residues, too. But, it is true that by this method you can get a scalable preparation method, with all the drawbacks of the preparation of a randomly substituted derivative.
good luck!
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Hi to all,
I'm wondering if glucose polymers such cyclodextrins, glycogen and more complex polymers, are metabolized by E.Coli.
Thank you
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Hello Antonio, 
At least glycogen is metabolized by E. coli. You can see an example here. http://jb.asm.org/content/187/4/1465.short
Also, its highly possible that E. coli is capable of metabolize such polymers since it has a broad metabolism capacity!
Best regards
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Since researchers are considering the use of cyclodextrins for removal of pollutants such as herbicide, heavy-metals, dyes etc through laboratory experiments. In practical vision, is it possible to remediate the environmental soil/water?
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Cyclodextrins have a hydrophobic core where low polarity organic contaminants will partition into from the water phase. This can be used to increase the solubility of many organic contaminants to increase contaminant extraction from soil and groundwater using cyclodextrin with water flushing or washing. Some cyclodextrins can also be used to complex and enhance the extraction of metals at the same time as organic contaminants.
Please see my attached paper:
Carroll, K.C., and M.L. Brusseau (2009) Dissolution, Cyclodextrin-Enhanced Solubilization, and Mass Removal of an Ideal Multicomponent Organic Liquid. Journal of Contaminant Hydrology, 106(1-2): 62-72.
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Can anyone highlight some papers relating cyclodextrins to 2D materials (single layer materials)? I am starting to work with 2D materials and trying to find a common ground/applications/sinthesys methods for these two kind of compounds. If anyone has some kind of review about it, I would be thankful!
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no permission :(
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I am performing a solubility test to compare the rate of solubility of a Tenoxicam-Betacyclodextrin complex to that of Tenoxicam alone.
For example,its known that 2.5 mg of Tenoxicam is excess in 25 mL of water.
Hence,i dissolve it accordingly and once saturated condition is achieved,the Tenoxicam is indeed,in excess.
On another note though, I estimated that 10.5 mg of my inclusion complex would consist of 2.5 mg of Tenoxicam.But,it could be lesser or higher than that right? And the parameter by which i am measuring the rate is time, hence I cannot add more inclusion complex once i have started the solubility studies.
How do I go about this? You may ask me in detail if there is anything I need to be clear about.
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Hi Deenesh,
Although it is somehow difficult to find your problem, because of lacking information, perhaps the followings might help you.
- The redissolution is depending on not only the composition (T-CD ratio) but also from many other parameters, like crystal form, porosity, etc. E.g. if you prepared your complex form aq. solution by freeze-drying, your sample is amorphous so the redissolution might be faster.
- How was the complex prepared? Did you determined the T content of the complex? And the water content? It might also happen that your complex contains water, which further reduces the T content. Usually, despite the e.g. 1:1 complexation, the guest content is below the "theoretical". You can find a publication where the T-bCD complex was prepared by kneading and the T content was approx. 80 % of the theoretical.
- Assuming that you prepared your complex according to the literature you can get higher than theoretical T content only if the complex contains some adsorbed T (because somehow the 1:1 complex is confirmed) 
- Please check that your T-CD complex is soluble water at all.
How do I go about this? First of all, determine the T content of your complex. (e.g. complete dissolution of the complex and calculate the T content by UV from a calibration curve). After it, try to create almost equal porosities of the solids (grinding in a mortar then sieve).
If it is possible, try to prepare the T-CD complex by different methods and compare the redissolution profiles. The best would be when you can get T from various sources to eliminate the errors of the potentially different powders.
Good luck!
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We are extracting curcuminoids from turmeric using ethyl acetate and IPA solvents.
The maximum recovery we get is about 55% of the total content of curcuminoids present in the raw material.
Is there any way to increase the recovery of curcuminoids? 
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The recovery may depend on the degree of hydration of your sample(i.e. whether it is fresh or dried).  Ethyl acetate will take up water in a hydrated sample, which will alter its characteristics as a solvent.. 
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Which group of thiomersal going to bind with cyclodextrin: either mercury ion or sulfur group? In some paper quoted that thiomersal with cyclodextrin reduces anti-microbial activity.
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This antiseptic and antifungal agent presents a chemical structure derived from benzoic acid. It is well described the inclusion complexes among different benzene derivatives and alpha- or beta-cyclodextrins (for the values of the association constants, see A. K. Connors Chemical Reviews; for the nature and the forces driving the inclusion processes, see K.A. Connors, J. Szjetli, Bender, Dûchene.....) , and you can ask directly his review articles to Professor T. Loftsson, currently at Research Gate).
In spite of thiomersal is a molecule with polar groups the lipophilic behaviour of the aromatic benzene ring favours its inclusion into the cyclodextrin cavity. The question is , which is more adequate alpha- or beta-cyclodextrins? Considering the size of the guest molecule is dificult to decide the most appropriate. On the other hand there are many articles describing the inclusion behaviour of aromatic molecules presenting ionizable group, such is the case of the derivatives of naphthalene-anline-sulfonate sodium salts that are described also by Professor Connors.
In summary, the inclusion into the clyclodextrin cavities is the result of different factors mainly the lipophilic behaviour of the guest molecules into the aqueous environment as well as the size and the shape of the molecules, the geometrical and spacial disposition of the guest molecules are also very important considering the capability of cyclodextrins for discriminate isomers.
If you need additional information, please send me a message and I will send to you some of my review articles describing the fascinating worlds of cyclodextrins.
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We have synthesized a push-pull 4,4'-bipyridine containing azobenzene dye and we have prepared its stoppered inclusion complexes (rotaxanes) with α and β cyclodextrin. (The inclusion complexes formation has been varified using various spectroscopic techniques).
Surprisingly, in the UV/Vis spectra of the rotaxanes, the molar extinction coefficient of the azo π-π* band increases (it gets even 50000 1/(M.cm) that is almost double as compared to the cyclodextrin-free dye. I cannot find any information which could explain this behavior, therefore I would be glad to read your opinion.
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May be you have some kind of pi-pi interaction or aggregation formation that can occur inside the CD.
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Curcumin we can measure in UV, but how can we measure the amount of cyclodextrin preset in the complex? In the following paper it has mentioned in 2.3 Formulation of the cyclodextrin complex of curcumin in that paragraph in 6th line you have mentioned that the "complex recovered contains 12 g/L curcumin and 93 g/L of Cyclodextrin.
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Extract with organic solvent then measured by UV or HPLC
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I have a novel compound that is insoluble in water. I have tried cyclodextrines and varying pHs. I have also tried to presolubilize in a wide variety of solvents (hexane, ACN, alcohols, DMSO, chloroform, acetone, xylene, etc) and found it is only slowly soluble in toluene. Is there a standard way to prepare a salt I should try? I also welcome other suggestions.
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Dear Wayne Briner,
you can prepare salt with organic or inorganic acids,
just dissolve your compound in the solvent as you mention your compound is soluble in toluene, then add organic or inorganic acid to it in drop wise manner, and stir it for 30-45 min to precipitate out. then either you can filter it in inert atmosphere or directly distilled off your solvent and you will get your compound in salt form.
if still can not solve the problem, then try some formulation solvent for the formulation in mixture,
currently we are using DMSO, EtOH, cremophore, PEG, Tween 80, glucose, water, PBS, saline....so on,
hope this is helpful to you...