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

Abstract

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, differential scanning calorimetry and hot stage microscopy confirmed that SCS are in crystalline state. Similarly, X-ray powder diffraction analysis revealed highly crystalline existence of pure drug, crystalline carriers and developed SCS. 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. 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.

Acoustic Cavitation-Assisted Formulation of Solid Lipid Nanoparticles using Different Stabilizers

“…The poor solubility of nearly 40% of drug molecules is the major reason for the failure in the main stream. , Based on the biopharmaceutical classification system (BCS), poorly water-soluble drugs have either class II or IV active pharmaceutical ingredients (APIs) . There are several approaches such as particle size reduction, , crystal engineering, traditional colloidal carrier system formulations, polymeric nanoparticles, and lipid-based nanoparticles to improve the bioavailability of BCS class II and IV drugs . Among the several nanocarriers, polymeric/lipid nanoparticles are the classic nanocarriers.…”

Melt extrusion with poorly soluble drugs – An integrated review

“…Pawar et al (2017) developed a solid crystalline suspension of the poorly soluble Efavirenz drug (M.P. = 139 °C) using xylitol and mannitol as crystalline carriers.…”

“…HSM can serve as a complimentary technique to DSC since it characterizes the melt behavior of the material tested at a specific temperature (Li et al, 2006). Pawar et al (2017) studied the crystalline dispersion of efavirenz in a carrier matrix using HSM. Djuris et al (2013) investigated the effect of temperature on the recrystallization of API in carbamazepine-Soluplus® solid dispersions through HSM.…”

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I

“…Various reports on solubility enhancement through HME were discussed in recent reviews [3,52,63], including solid dispersions of tadalafil [67], co-amorphous system of indomethacin/arginine [68], solid crystalline suspensions of efavirenz [69], solid solutions of artesunate [70], and ternary inclusion complexes of itraconazole/cyclodextrin [71]. In this section of this review, we present new reports on HME applications for drug solubility enhancement for the readers' interest.…”