Dude maybe your strings are getting too old and arent sounding what they used too?
2 guitars. If you want it to be perfect then you're going to need at least 2 guitars.

Tuning and intonation are all about pressures and lengths. Change the string guage up or down right after a good set-up and it's all out of whack.

Same concept for Intonation when you start dropping tunings.

Another thing to consider is that you're really supposed to change strings 1 at a time instead of taking all 6 off and replacing at one. Only reason I say that is.....Mostly the premise behind this is that you want to Avoid sudden pressure changes on your neck..... can mess up the angle, bow, and consequently the intonation.

So by the same logic changing tunings (tension) is going to have the same effect over time.

Bottom line is a guitar for each tuning.
96 Gibson Les Paul Goldtop
95 Strat w/ Lindy Fralins
Ibanez JS1000
Orange AD30HTC
Vox AC30
Blue Alnico Cab
Budda Wah
Barber Tone Press
Keeley NOVA Wah
Pederson Strobo
Keeley TS-808
HBE Chorus
T-Rex Delay
Red Witch Moon Phase