Yes, its possible by Adding OpenType Features to the font. However, not many applications support OpenType glyph substitutions.
If you enable the complex text features in Windows, Notepad will support glyph substitutions, e.g. converting f+ i to fi but WordPad and Word (AFAIK) do not, and neither does OpenOffice. I use macros or find and replace to make the substitutions manually although my fonts do include OpenType features.
Notepad Ligatures.png