pH effect on Ursodeoxycholic acid

[el gringo]

Does anyone know what causes Ursodeoxycholic acid to gel in aqueous solution at pH 1.2 and 8.0, but not at pH 4.5.? I make UDCA capsule blend then fill into gelatin capsule shell by hand and no gelling occurs. When we fill blend into capsule shell using automated equipment, we see the gelling effect at pH 1.2 and 8.0. The automated encapsulation is not considered high energy. It doesnt compress the blend so hard that it produces a solid mass; capsule contents are a free flowing powder after encapsulation. I think if we can understand why the gelling occurs, then we can prevent it from happening. Does anyone know how the crystal structure might change during encapsulation, and how it might account for what we see?

[Horza2002]

I'm not 100% sure, but these are some ideas that I came up with:

 

Under the acidic conditions you mentioned, it is possible that the carboxylic acid and one of the hydroxy groups in the compound are undergoing an esterifcation reaction so that you end up with a polymer of ursodeoxychloic acid.

 

Under the basic conditions, you will deprotonate the carboxylic acid to give the conjugate salt of the compound. Its possible, because ursodeoxychloic acid is very hydrophobic, that the salt forms an emulsion type structure in the water; hence appearign as a gel