Solubility limits and what a cloudy solution is telling you

Solubility limits and what a cloudy solution is telling you — setting out what I have, and where I think it stops being reliable.

The question about solubility limits that I actually want answered is the second one below. The first is context and I have kept it short.

Both are stated with units, and I have said what I already checked so that nobody repeats it.

Antioxidants: compounds that prevent oxidation (which damages peptides) are sometimes included. Methionine oxidation is a common degradation pathway and antioxidants help prevent it.

I would rather say I do not know than round it up to an answer.

The opening post put the caveat in the right place and I want to underline it.

If you are new and reading this thread for the answer to solubility limits: the answer is conditional, the conditions are in the third reply, and the rest of the thread is worth skipping.

Building on post #3 rather than restating it.

Buffer choice affects both solubility and stability, and the two do not always point the same way. A formulation is a compromise between them rather than an optimum for either.

No disagreement from me. Posting only so the question does not look ignored.

Isotonicity: an isotonic solution has the same osmotic pressure as blood. Non-isotonic solutions can cause discomfort on injection. Injectable peptide solutions are formulated to be isotonic.

That distinction has done more work for me than anything else in this category.

Excipients and their purposes: mannitol, sucrose, or other sugars in lyophilised formulations protect the peptide during drying and storage. They are not impurities; they are functional components.

The disagreement above is smaller than it looks once the terms are fixed.

Post #7 describes the usual case. This is about the unusual one.

Solubility limits came up in a thread eighteen months ago and was answered well. I cannot find it, which is itself the problem, so here is the reconstruction.

Freeze-thaw cycling is harsher on a solution than sustained cold, because the ice-water interface is where damage occurs. A single freeze is a different event from five.

Post #9 is the version of this I will quote in future. One addition.

Solubility limits is worth one more sentence than it usually gets, and the sentence is the one about how the number was arrived at.

Having read the whole solubility limits thread before replying: the question in the first post has not actually been answered yet, and three of us have answered a nearby one instead.

An honest declaration on solubility limits: I have a prior here and it is strong enough that you should weight what I say downward. Stating it rather than hiding it.