Hello! We have a rather insoluble drug in aqueous buffers but it gets dissolved in DMSO. It also remains soluble after we add 95% of PEG300. Would 5% DMSO/95% PEG300 would be acceptable for oral gavaging mice every day for 30 days approximately?. Unfortunately, if we add water or saline, the drug comes out of solution. I would really appreciate it if anybody has any input on the matter. Thanks!!
Then the drug will precipitate in gut anyway. You might consider to make a suspension instead (less toxic). Alternatively, if you have a supersaturation you can prolong the time before precipitation by addition of a surfactant or a polymer.
We have used 70% propylene glycol to dissolve a highly hydrophobic drug and oral gavage gave us favorable results. Although, the dosing was twice a day for 7 days. You may also want to consider the toxicity of PEF300 on 30 days administration. PEG300 has low toxicity, but it can cause kidney and liver damage on long-term administration (https://www.bibra-information.co.uk/downloads/toxicity-profile-for-polyethylene-glycol-300-1991/).
You can also try DMSO/Ethanol/saline. Using a surfactant like sodium stearate can also solve the solubility issues.
The oral LD50 for DMSO is ~7 mL/Kg, Means the safe dose is ~0.7 ml/kg for mouse. Even if you add water or precipitates in the stomach, your API is in amorphous state and it is OK to dose this way. Many people use suspensions.