Conjugation of Hot-Melt Extrusion with High-Pressure Homogenization: a Novel Method of Continuously Preparing Nanocrystal Solid Dispersions

Abstract

Over the past few decades, nanocrystal formulations have evolved as promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods of preparing nanocrystal formulations, such as spray drying and freeze drying, have some drawbacks including high cost, time and energy inefficiency, traces of residual solvent, and difficulties in continuous operation. Therefore, new techniques for the production of nanocrystal formulations are necessary. The main objective of this study was to introduce a new technique for the production of nanocrystal solid dispersions (NCSDs) by combining high-pressure homogenization (HPH) and hot-melt extrusion (HME). Efavirenz (EFZ), a Biopharmaceutics Classification System class II drug, which is used for the treatment of human immunodeficiency virus (HIV) type I, was selected as the model drug for this study. A nanosuspension (NS) was first prepared by HPH using sodium lauryl sulfate (SLS) and Kollidon® 30 as a stabilizer system. The NS was then mixed with Soluplus® in the extruder barrel, and the water was removed by evaporation. The decreased particle size and crystalline state of EFZ were confirmed by scanning electron microscopy, zeta particle size analysis, and differential scanning calorimetry. The increased dissolution rate was also determined. EFZ NCSD was found to be highly stable after storage for 6 months. In summary, the conjugation of HPH with HME technology was demonstrated to be a promising novel method for the production of NCSDs.

A top-down technique to improve the solubility and bioavailability of aceclofenac: in vitro and in vivo studies

“…15 Of late, another newer technique that is, hot-melt extrusion with HPH is slowly gaining importance. 16 In the present study, the nanocrystals approach to improve the solubility of a poorly soluble drug aceclofenac (ACF) was attempted using wet milling method by utilizing Quality by Design (QbD) approach.…”

“…Most of these products rely on the use of media milling and HPH approach. 16 Both these processes carry out size reduction in the liquid suspension form. Hence, careful selection of appropriate type and concentration of stabilizers is the key in the formation of stable nanosuspension.…”

Preparation, characterization, and pharmacokinetics in swine of a florfenicol enteric formulation prepared using hot‐melt extrusion technology

“…HME can also increase the stability of microencapsulated drugs (Sarode, Sandhu, Shah, Malick, & Zia, 2013). Furthermore, HME has various advantages, such as low cost, good time and energy efficiency, the ability to remove residual trace solvent, and easy continuous operation (Ye et al, 2016).…”

Recent Approaches of Solid Dispersion: A New Concept Toward Oral Bioavailability Sabitri Bindhani* , Snehamayee Mohapatra

“…Ye et al [27] had described a Novel Method of Continuously Preparing Nanocrystal SDs of poorly soluble drug Efavirenz. They had combined high pressure homogenization and hot melt extrusion (HME) which was proved to be a promising novel method for the production of nanocrystals SD.…”