Three people were arrested along the N1 corridor between Gauteng and Cape Town.
The Hawks said the three were arrested on Sunday along the national highway, near Beaufort West, with the help of the dog unit.
Hawks spokesperson Zinzi Hani said a tip-off resulted in an intelligence gathering operation. After a thorough investigation, a white pick-up truck was pulled over and searched. At least 33 500 Mandrax tablets were allegedly found in the vehicle.
On Tuesday, Nkosinathi Gamede, 37, Ndumiso Buthelezi, 27, and Blessing Pasi, 34, appeared in the Beaufort West Magistrate's Court to face charges related to the bust.
The case was remanded until 27 September for the State to get bail information.
Previous busts along the N1 to Cape Town include a haul of dagga worth R1 million between Paarl and Klapmuts, around R1 million on the N1 near Beaufort West, and R1.4 million worth of drugs in Laingsburg.