If you are starting and ending the ride in Leakey the Sisters loop is about a hundred miles and is easily done in 2 1/2 or 3 hours. Medina is not on the loop but the Frio Canyon Motorcycle Stop is and I consider it a must stop. If you ride the loop counter clockwise the Frio Canyon Motorcycle Stop is just before you arrive back in Leakey.
The Twisted Sisters is one of my favorite Texas rides and I usually ride it every time I am in the area. Enjoy the ride and watch for deer.