On the subject in the title: Solubility limits and what a cloudy solution is telling you Working notes rather than a conclusion.
Reading back through what has been written here about Solubility limits, three questions come up every time and only one has ever been answered properly.
Listing all three, with what I think the state of the answer is for each, so the thread can start further along than the last one did.
Where I part company with the opening post, and it is a narrow parting.
Overfill in a vial is deliberate and accounts for the volume unrecoverable at the end. It is not generosity and it is not a bonus dose.
On Solubility limits, the part that usually goes wrong is that the question is asked as though it has one answer. It has a range, and the width of the range is the interesting bit.
If you can post the two or three numbers you are working from, several people here will check the arithmetic rather than argue about the conclusion.
I think the Solubility limits question is answerable and has not been answered, which is a more optimistic position than most of this thread.
Where the Solubility limits reasoning breaks down for me is the step from the group result to the individual case. That step is almost never argued for.
The arithmetic in post #6 is right; the assumption feeding it is the part to check.
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.
I am reporting what happened, not recommending it.
The strongest argument against my own position on Solubility limits, stated as well as I can state it, since nobody else has yet.
On Solubility limits: the maintained page in the documentation commons covers the general case with citations and a review date, which is more reliable than any reply here including this one.
Post #11 answers the question as asked. The question underneath it is different.
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.
Fine by me. I had wanted a stronger conclusion and there is not one available.
Small correction to my own earlier position on Solubility limits. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.
Post #15 is right about the mechanism and I think understates the practical bit.
Where I have landed on Solubility limits, having got it wrong once in public: the direction is clear, the magnitude is not, and anyone quoting a precise magnitude has borrowed it from somewhere that did not measure it.
The confident answers on Solubility limits and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.
Residual moisture in a lyophilised product is a stability determinant and is measured by Karl Fischer titration. Above a few per cent, shelf life shortens considerably.
That is the shape of it. The detail is where I would expect to be corrected.
Taking Solubility limits seriously for a moment rather than deflecting: the honest position is that the community has observations and no controlled comparison, and those two things support very different sentences.
The reason Solubility limits keeps being re-asked is that the answer is conditional and people quote it without the condition. It is not that the answer is unknown.
Light sensitivity varies enormously between peptides depending on the residues present. Tryptophan-containing sequences are the ones where it matters most.
The short answer was in the first line; everything after is the working.
Post #18 put the caveat in the right place and I want to underline it.
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.
I have seen it go both ways, which is why I hedge.
Trying to state the Solubility limits position in a way that someone who disagrees would recognise as fair, because I do not think the version in this thread passes that test.
Fill volume and headspace: the amount of solution in a vial and the air above it affect how much the solution is exposed to oxygen during storage. Less headspace means less oxygen exposure.
I keep a log of this specifically because memory is unreliable about it.
Nothing to add on the substance. Thank you for taking the question at face value.
Osmolality of a home-reconstituted preparation is whatever the diluent makes it, and nobody is measuring it. In practice at these volumes it is a comfort question.
Benzyl alcohol as a preservative is also a solubiliser for some peptides, which is an incidental property that occasionally matters.