THE USE OF LOCAL THERMODYNAMIC PATH FOR QUALITY PROBLEMS DURING CONVECTIVE DRYING

ABSTRACT

The pharmaceutical drug under investigation in this paper has two hydration states with several polymorphic forms. The two hydration states are tetrahydrate and monohydrate. Two polymorphs of monohydrate are in competition. Process must lead to the metastable therapeutic form (TF) although the non therapeutic form (NTF) is the stable one. The sensitive stage is drying

From desorption isotherms coupled with infrared spectroscopy, an equilibrium diagram of the different forms versus the external conditions (temperature and relative humidity) is performed. A macroscopic study achieved on tangential convective drying shows that the equilibrium diagram does not insure to obtain the metastable form after drying. It is deduced from an experimental analysis of internal temperature and water activity that the final form depends on the local thermodynamic path. Indeed, if NTF favourable conditions occur within the product during the process, this irreversible form remains although the final form predicted by the diagram is TF

It is concluded that NTF is promoted by a slowing down of transfers and an enhanced water vapour removing (greater exchange surface).

Key Words and Phrases:

• equilibrium diagram
• hydrates
• metastability
• pharmaceutical drug
• polymorphic form