If the covers will be printed on a different stock of paper than the interior pages, they will need to be in different files. Otherwise it's okay to keep them in the same file.
The layout should be in a layout software such as InDesign, Quark or Pagemaker. Do not attempt to do a publication in Word or Illustrator/Corel Draw. Most print shops will not take them. If they take a Word file, they usually upcharge for the printing process.
Always make sure your page increments are in 4's or 8's depending on how many pages will print on a spread. If it's a perfect bound book, it doesn't matter how many pages.
If you have any other questions, feel free to ask.
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