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?
Hi,
Cyclodextrin nature and drug:cyclodextrin ratio are the key parameters to obtain a true inclusion. Did you check the stability constant from phase solubility diagram, this will give information on the power of the interaction.
Best regards
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.
Dear Gilles Dollo, Laszlo Jicsinszky and François-Xavier Legrand,
First of all, thank you for your answers.
We did not do the phase solubility diagram study, because we used the rates in the article. However, it is not clear how the ratios are so accurate due to they are doing filtering in these studies. Perhaps the ratios should be determined by quantifying of the sample after complex preparation.
In kneading method we obtained less suitable results in comparison with freeze drying. For this reason we decided to continue with freeze drying.
We looked at the XRD in the first phase of the study, but we'll also do NMR analysis. I hope, we can get better results after NMR.
Hi Ozlem,
If you have the materials - i.e. not writing a review or a general part of something -, never use literature data, they can be use as base information but the exact values should always be measured personally. This is valid somehow for the phase solubility studies: the base solubility (solubility of your substance in lack of CD) should be determined always yourself! If the deviation from the literature is too large, then you need to think where is the error.
Good luck,
Laszlo
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