Melt extrusion with poorly soluble drugs

作者：Shah Sejal; Maddineni Sindhuri; Lu Jiannan; Repka Michael A^*

来源：International Journal of Pharmaceutics, 2013, 453(1): 233-252.

DOI：10.1016/j.ijpharm.2012.11.001

• Melt extrusion
• Poorly water soluble drugs
• Dissolution rate enhancement
• Solid dispersion
• Amorphous system
• Solid solution
• Thermoplastic polymers

Melt extrusion (ME) over recent years has found widespread application as a viable drug delivery option in the drug development process. ME applications include taste masking, solid-state stability enhancement, sustained drug release and solubility enhancement. While ME can result in amorphous or crystalline solid dispersions depending upon several factors, solubility enhancement applications are centered around generating amorphous dispersions, primarily because of the free energy benefits they offer. In line with the purview of the current issue, this review assesses the utility of ME as a means of enhancing solubility of poorly soluble drugs/chemicals. The review describes major processing aspects of ME technology, definition and understanding of the amorphous state, manufacturability, analytical characterization and biopharmaceutical performance testing to better understand the strength and weakness of this formulation strategy for poorly soluble drugs. In addition, this paper highlights the potential advantages of employing a fusion of techniques, including pharmaceutical co-crystals and spray drying/solvent evaporation, facilitating the design of formulations of API exhibiting specific physico-chemical characteristics. Finally, the review presents some successful case studies of commercialized ME based products.

• 出版日期2013-8-30