Sample size for 4-period 4-sequence crossover BE study [Power / Sample Size]

Hi,

I am in the process of conducting a sample size calculation for a crossover BE study. There are four-treatments (2xreference dosages & 2xtreatment dosages) & I plan to use the Williams' design as follows:

ABCD
BDAC
DCBA

The coefficient of variation from previous studies is 20% & I am assuming the true test reference ratio to be between 0.95 and 1.05. I want to demonstrate bioequivalence (0.80-1.25) at 90% power at the 5% level.

Using these figures, if it was a standard AB/BA crossover, I estimate that I would require 12 individuals to complete each arm - is this correct? I am unsure how this calculation is extended to fit the 4x4 design - do I simply randomise 12 more individuals to each of the remaining two sequences?

Further, if I planned to have just 1 treatment dose changing the design as follows:

ABC
BCA
CAB

Is it reasonable to randomise 12 individuals per sequence?

I really appreciate any help on this question.

Best wishes,
Bryony