Mechanical properties and drug release of venlafaxine HCl solid mini matrices prepared by hot-melt extrusion and hot or ambient compression

Abstract

Objective/significance: To elucidate the role of plasticizers in different mini matrices and correlate mechanical properties with drug release.

Methods: Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug, Eudragit^® RSPO the matrix former and citric acid or Lutrol^® F127 the plasticizers. The matrices were characterized for morphology, crystallinity, and mechanical properties. The influence of plasticizer’s type and content on the extrusion pressure (P_e) during HME and ejection during tableting was examined and the mechanical properties were correlated with drug release parameters.

Results: Resistance to extrusion and tablet ejection force were reduced by Lutrol^® F127 which also produced softer and weaker pellets with faster release, but harder and stronger HC tablets with slower release. HME pellets showed greater tensile strength (T) and 100 times slower release than tablets. P_e correlated with T and resistance to deformation of the corresponding pellets (r² = 0.963 and 0.945). For both HME and HC matrices the decrease of drug release with T followed a single straight line (r² = 0.990) and for HME the diffusion coefficient (D_e) and retreat rate constant (k_b) decreased linearly with T (r² = 0.934 and 0.972).

Conclusions: Lutrol^® F127 and citric acid are efficient plasticizers and Lutrol^® F127 is a thermal binder/lubricant in HC compression. The different bonding mechanisms of the matrices were reflected in the mechanical strength and drug release. Relationships established between T and drug release parameters for HME and HC matrices may be useful during formulation work.

Keywords:

• Hot-melt extrusion
• plasticizers
• pellets
• compression
• mini tablets
• tensile strength
• drug release
• diffusion coefficient
• venlafaxine HCl

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The work was funded by the Research Program for the Development of Industrial Research in Greece and Technology Growth (NSRF2013) granted to VIANEX SA, Athens, Greece to whom and Dr Anthony Avgerinos we are very grateful.