The most common and most likely answer to this crossword clue is the 5 letter word TWIXT
I've seen this crossword clue in The Times
T
W
I
X
T
Buddy explains!
The straight part
We know that "Once in the middle of" is the straight/definition part of the clue. The straight part is often a synonym or definition, in this case once in the middle of = twixt.The cryptic/wordplay part
In cryptic crossword there's often an wordplay/cryptic part as well.This part involves a more complex hint, such as an anagram, homophone, hidden word, etc.
Sadly, We don't have an explanation for this specific crossword clue yet.
What does TWIXT mean?
TWIXT preposition- Betwixt, between