Rai Bachchan, whose pregnancy was announced earlier this week, was originally approached to work opposite husband Abhishek Bachchan in the comedy, The Times of India reports.
"The fact that Aishwarya and Abhishek are going to be parents is far more important than anything to do with my film. The nature of the part that she was playing no longer suits her," said Santoshi.
Zinta, who has been largely absent from the film industry since 2008, is now being linked to the role by the media.
Santoshi, however, has denied that he is looking for a replacement for the former Miss World.
"It's a project that I've written specially for her. The role cannot be played by anyone else. I will start it as soon as she is ready," he said.
The Bachchans have appeared together in a number of films including Guru, Dhoom 2 and last year's Raavan.
Rai Bachchan told Digital Spy last year that she wanted to "bring a different Aishwarya" to her audiences with each release.