Abdel-Halim Khaddam, who now lives in Paris, told Germany's weekly Der Spiegel magazine on Saturday that al-Assad was facing growing pressure from economic problems at home and the international investigation into the killing of Rafiq al-Hariri, the former Lebanese prime minister.
Khaddam, who accuses al-Assad of ordering al-Hariri's murder, said: "His fall has already begun. I don't think his regime will last out this year."
The former vice-president, for 30 years a confidant of al-Assad's late father, Hafez al-Assad, left the government in June.
He has been accused of treason and expelled from the ruling Baath Party after a series of verbal attacks on the president.
Khaddam told the Associated Press earlier this month he wanted political change in Syria, saying the Damascus government had outlived its time and was unlikely to survive much longer.
Asked whether he supported regime change in Syria, Khaddam replied: "Yes." He also said that he had no personal interest in leading the drive to remove al-Assad.
Islamists and Baathists
But when asked by Der Spiegel whether he was seeking to form a government-in-exile, he said: "That is correct."
"One should not make the mistake with the Syrian Baath Party that the Americans made with the Iraqi Baath Party"
Abdel-Halim Khaddam, former Syrian vice-president
Khaddam said he would be ready to work with Islamist leaders, whom he called "part of the rich Islamic mosaic that defines the basic character of our country", and the Baath Party.
"I would not rule out any political group that sticks to the basic rules of democracy," he said.
"One should not make the mistake with the Syrian Baath Party that the Americans made with the Iraqi Baath Party.
Order to kill
"The majority of Baathists in Syria have long ago turned against the regime. They see the government's mistakes every day."
Khaddam also repeated the allegation he made earlier this week that al-Assad had ordered the murder of al-Hariri.
"I'm convinced: the order came from al-Assad," he said. "He is an extremely impulsive man, he is always losing his cool."
Syria has denied any role in the bomb blast that killed al-Hariri and 22 others in Beirut last year.