Making Complexes

The successful complexation of a sparingly water soluble guest compound by a CMCyclodextrin depends on three things:

1. concentration of the CMCyclodextrin
2. inherent "includability" of the guest compound
3. particle size

If there are only a few guest molecules available, complexes will take a long time to form and even longer to establish equilibria, even when stability constants are large. Therefore molecularization tactics such as:

• hydration
• solvation with water miscible cosolvents
• melting
• blending
• sonicating
• kneading

can be used to improve both the rate and amount of incorporation.

More details on:

• solution dynamics
• temperature effects
• specific solvents
• oil as a guest
• volatile guests
• gases as guests

and specific techniques such as:

• coprecipitation
• slurry complexation
• paste complexation
• dry mix and heat
• extrusion

are available on request.

Most complexes are stable to ambient conditions of heat, relative humidity and light. However, the recommended method of storage is in a tightly closed container kept in a cool, dry place out of bright light. Under these conditions, most complexes will be stable for many years.

General method of complexation with Trappsol® CMCyclodextrin's

In general, powdered CMCyclodextrin is dissolved in water, the compound is added, stirred for some length of time, filtered, and water is removed.

Taking into account the volume expansion, make an aqueous solution with the CMCyclodextrin. The compound to be complexed should be added in excess - small additions followed by stirring or sonicating until a clear solution develops can be repeated until no more active ingredient will go into solution. Some compounds may require several days of stirring to reach equilibrium; others may take only hours. Checking a small filtered sample of the complex by UV absorption or TLC may show how the incorporation rate is increasing over time.

Because the formation of most complexes is exothermic, lowering the solution temperature should favor complex formation. The cyclodextrin solution can be prepared with a buffer to improve the incorporation of acidic or basic compounds.

End filtration by an appropriate method, usually resulting in a clear solution, can be the last step. Or, the solution can then be dried by lyophilization or spray drying, resulting in a fluffy powder easily resolubilized in the same concentration as the original solution. Note that a less concentrated solution of the dried complex may result in precipitation, due to the failure to achieve a critical or minimal concentration of the CMCyclodextrin.

Using a co-solvent to dissolve the compound before adding it to the CMCyclodextrin solution does not usually increase the includability, but may greatly decrease the stirring time necessary to achieve equilibrium. This may be helpful if you are complexing an unstable material. In this case, remove the co-solvent through rotary evaporation after filtration. Resolubilize the dried material with the same amount of water that was used to make the original CMCyclodextrin solution, and a clear solution of the complex should be obtained. This can be followed by lyophilization or another drying method.

Complexation of proteins can be achieved using the same methods. However, the CMCyclodextrin solution should be in much lower concentration, usually between 1- 5%w/v.