Effect of plasticiser type on the hot melt extrusion of venlafaxine hydrochloride

Abstract

Objectives: During hot melt extrusion (HME), phase changes and interactions due to thermo-mechanical stresses affect the drug incorporation into polymeric matrices. Two HME compositions of venlafaxine HCl with Eudragit RSPO (Evonic, Darmstadt, Germany) as the matrix polymer and either citric acid monohydrate (CAMH) or Lutrol F127 (BASF, Ludwigshafen, Germany) as plasticisers were compared. Methods: Miscibility and extrusion temperatures were elucidated based on solubility parameters and differential scanning calorimetry. Thermal changes in the extruded melts and their respective physical mixtures were compared. Powder X-ray diffraction was applied to detect changes in crystallinity and fourier transform infrared (FT-IR) spectroscopy for chemical interactions. Key findings: Both plasticisers (15%) enabled extrusion easily. With Lutrol, the drug remained crystalline, whereas with CAMH a single-phase amorphous transparent extrudate was obtained. Differences between the thermographs of extruded and physical mixtures indicated the importance of mechanical stresses in the single-screw extruder. In the FT-IR spectrum of Eudragit/CAMH/drug extrudate, the abscence of the peak due to venlafaxine OH and the merging of the two peaks due to CAMH carbonyl, into one, indicated esterification. Conclusions: CAMH and Lutrol have different reactivities towards venlafaxine HCl and also different plasticising mechanisms for Eudragit RSPO because of hydrogen bonding and because of similar overall molecular attractive forces, respectively.