Giri if your compound is having any ree hydroxyl groups then better you can make glycosides of your compound which is makes your compound highly soluble. 

Hi Giri,

 Yes, you may have chances to increase the aq. solubility with cyclodextrins. If you want to dissolve your compound for oral administration then you can use practically any available CDs because they are very poorly absorbed, but native ones can be the best. For parenteral, particularly for iv., administration it is better to use pharmaceutically accepted CD derivatives.

 The enhancement of water solubility is high depend on the molecular structure of your compound. At first, I would recommend (2-hydroxy)propyl beta- or gamma-cyclodextrin (HPb- and gCD), partially acetylated (DS~7) beta- or gammaCDs, or native gamma CD (or occasionally alpha) because these are biocompatible with a living organism other than bacteria or funghi and these usually do not form insoluble complexes, unlike betaCD.

 In some cases the HP-cyclodextrins show DS dependent solubilization power (DS= number of substituents/CD ring; do not mix it with MS which means substituent/glucopyranose unit and a consequence of this definition the identical MS means different DS, because you need to multiply this value with the number of constituting units - these two values are used intensively for randomly substituted CDs).

  Partially acetylated CDs are in many cases are better than methylated ones, although they are not in Pharmacopeias.

 Theoretically the randomly methylated bCD is also OK but methylated CDs are very hemolytic ones and it is not sure that the animals can survive the treatment, they are not registered as pharmaceutical additive for parenteral use.

 Good luck!

Hello Mr. Girdhar,

There are many articles on solid dispersion and cyclodextrin. Before approaching any work thorough knowledge on that particular topic is necessary.Size of inner cavity of CD, and molar volume and functional groups of drug are important consideration , and type of CD: whether it is pharmaceutically accepted or not.Whether complex involves strong chemical bond or weak physical bond , which is desirable or not.There are many methods to enhance solubility of a drug.There are books , publication available o this topic. 

Dear Contributors, Thanks a lot for all your suggestions.  

@Dr Laszlo Jicsinszky-thanks for your detailed explanations about use of cyclodextrin (CDx). I tried HP-CDx to make a complex with my compound.

@Prof Jasmina Khanam-Thanks for your suggestions. yes, I'm going through literature for the better understanding of this phenomena.

@Prof Anwar A Hussain-Thanks for your suggestion.

My apologies as this is a commercial sensitive project so can't share the compound structure.

a quick query again, is it required to be in solution form for both CDx and compound to form a complex?

My compound is insoluble in most of the organic solvents except DMF (m.p. 182 degree C). I dissolved both CDx and comp in DMF - then mixed together and added water - it looks a clear solution but still need to analyse by spectroscopic methods to confirm.

Thanks, Giri

Dear Giri,

 There are practically solventless technologies to prepare complexes, like kneading or ball milling. In both cases it is advisable to add some - couple of percent - water or EtOH-water but HPCDs are very soluble in these solvent(mixture)s. Sometimes after ball milling it is difficult to remove the product form the balls/jar. But, as I am writing it later, the best and fastest to get water soluble complex is the stirring or ultrasonicating your compounds and the HPCD solution, filter and freeze-drying the solution. I am afraid you cannot pass the recording of the solubility isotherm(s).

 I would recommend the following way:

- prepare the solution from the HPCD (0.5-20% of HP to get the so-called solubility isotherm to determine the complex stoichiometry and solubilizing power), and please, remember that the HPCDs may contain 2-6% water.

- Then stir your compound and the solution (as vigorously as you can) overnight and then filter the suspensions.

- From the solution determine the concentration of your compound, then

- make a graph to see the solubilization characteristic. It is better to make two graphs, one as mass and the second as molar. From these graphs you can deduce which is the (almost) optimal concentration of the host for solubilizing.

 As you said it is a commercial sensitive project, so I would recommend you to record the solubility isotherms with all available DS for HPbCD (~3, ~4.5, and ~6.3) to see if there is a DS dependent complexation, and with HPgCD.

 For preparative purposes you can use also the methods for getting the solubility isotherms by freeze-drying the filtered clear solution. By this method your composition will be almost surely redissolved in water without insolubles. When you get the complex by kneading/ball milling you have serious chance to find insolubles - although, it is true that in those cases will be the highest the guest:host ratio.

 For oral administration even 30-40 % of HPbCD can be used. For intravenous application the more concentrated (>10 %) HPCD solution might cause kidney damages due to the high osmotic properties.

 Please, also note, that because these compositions are complexes it might happen that dilution of a solution may result in the dissociation of the complex and precipitation of your guest. This is another reason why the solubility isotherm is important.

 good luck!

Dear Dr Laszlo Jicsinszky, I highly appreciate your time and efforts for supporting me regarding this research problem. I will try to implecate your suggestion and let you know about the outcomes.

Thank you so much, Giri

Yes, especially B-Cyclodextrin and it gives excellent results.

Hi Ahmed,

Unfortunately, betaCD often forms insoluble complexes. Additionally, that CD is inappropriate for iv administration.