Solid crystal suspension of Efavirenz using hot melt extrusion: exploring the role of crystalline polyols in improving solubility and dissolution rate

摘要

The poor aqueous solubility of drugs has emerged as a major issue for pharmaceutical scientists from many decades. The current study explores the manufacture and development of a thermodynamically stabilized solid crystal suspension (SCS) of poorly water soluble drug efavirenz via hot melt extrusion. Efavirenz is a non-nucleoside reverse transcriptase inhibitor and belongs to BCS class II. The SCS was prepared using pearlitol and xylitol as a crystalline carrier. The drug-excipient blend was processed by hot melt extrusion with up to 50% (w/w) drug loading. Physico-chemical characterization of the SCS conducted via a scanning electron microscopy showed crystalline morphology. The solid state analysis undertaken by using differential scanning calorimetry and hot stage microscopy confirmed that SCS are in crystalline state. Similarly, X-ray powder diffraction analysis revealed that pure drug, crystalline carriers and developed SCS are in crystalline state. The FTIR chemical imaging analysis of SCS formulations showed a homogeneous drug distribution within respective crystalline carriers while an advanced chemical analysis via atomic force microscopy and Raman analysis complemented the foregoing findings of the FTIR imaging. The developed SCS1 formulation showed up to 81 fold increase in the solubility and 4.1 fold increase in the dissolution rate of the drug compared to that of the bulk substance. Surprisingly, the developed SCS formulation remained stable for a period of more than one year at accelerated conditions inferred from dissolution studies. It can be concluded that the SCS approach can be used as an alternative contemporary technique to enhance the dissolution rates of many other poorly water-soluble drugs by means of thermal HME processing.