That is the biggest issue when it comes to picking,no worries,
we all fight the same battle here.
With enough practice you'll overcome it.
All you have to do it to prepare you picking hand's muscles
for motions like that and here's an exercise you could try.
Play only 2 note,on different strings,on low E and A strings per example.
Start with note on A with downstroke and go for note on low E.
You'll face the issue right there,and again when you go back to note on A string.
Just loop the pattern and play it for a while,
muscles need time to adapt.
Take it easy,no need to rush,try to play it clean
with as much accuracy as possible.
Then try opposite thing,start with note on low E,play it it upstroke
and go for note on A string,again the same issue and
more reasons to loop the pattern over and over.
Speaking of 3nps and 2nps patterns,
you can
avoid this problem only for 2nps pattern
and not for 3nps patterns,here's how.
Lets say you play 2nps Pentatonic,ascending lick.
Start with an upostroke and picking motion will
be just as wanted.
If you go for descending lick then start with a downstroke
and picking will be fine.
But as an exercise always try same thing on both ways,
to prepare yourself better for upcoming licks in the future.
As for 3nps,you said you have no troubles with it
cause you end with downstroke and next string you're aiming at is string bellow.
That is correct,but what about next one?
You'll end with an upstroke this time and next string will be below once again.
So it's like this,do not try to get away from this motion,
face it and make yourself comfortable with it.
That's actually the reason why I made the lesson
Upstroke Focus,
check it out,perhaps it'll help a bit.