دانلود رایگان ترجمه مقاله انبساط کنترل شده محلول فوق بحرانی روشی مقاوم برای تولید نانوذرات دارویی خالص (نشریه الزویر 2016)

انبساط کنترل شده محلول فوق بحرانی: یک روش مقاوم برای تولید نانوذرات دارویی خالص با توزیع-اندازه باریک

Controlled Expansion of Supercritical Solution: A Robust Method to Produce Pure Drug Nanoparticles With Narrow Size-Distribution

Abstract

We introduce a robust, stable, and reproducible method to produce nanoparticles based on expansion of supercritical solutions using carbon dioxide as a solvent. The method, controlled expansion of supercritical solution (CESS), uses controlled mass transfer, flow, pressure reduction, and particle collection in dry ice. CESS offers control over the crystallization process as the pressure in the system is reduced according to a specific profile. Particle formation takes place before the exit nozzle, and condensation is the main mechanism for postnucleation particle growth. A 2-step gradient pressure reduction is used to prevent Mach disk formation and particle growth by coagulation. Controlled particle growth keeps the production process stable. With CESS, we produced piroxicam nanoparticles, 60 mg/h, featuring narrow size distribution (176 ± 53 nm).

1 Introduction

Introduction Particle production based on supercritical carbon dioxide (scCO2) is efficient, inexpensive, and ecological.1 These kinds of bottom-up technologies form particles by recrystallization.2 CO2 is the most common solvent in supercritical processes because its critical temperature and pressure are relatively low, 31
C and 74 bar.3 Furthermore, CO2 is “Generally Recognized As Safe” by the Food and Drug Administration; it is neither flammable nor toxic. The prepared particles are pure, and the obtained polymorph can be controlled.4-6 Supercritical particle production allows using a 1-step preparation process.2 This simplifies the particle production, which, for example, in common industrial ball milling techniques requires many steps and excipients. Moreover, current nanoparticle technologies feature limited batch size and often require organic solvents.7

Particle production techniques using scCO2 use scCO2 as solvent, as solute, or as antisolvent.5,8 Rapid expansion of supercritical solutions (RESS) is a solvent- and excipient-free production method.9 It has been used to micronize pharmaceutics1,4,10 and to produce nanomicron- and submicron-size drug particles.11-21 For example, piroxicam, the model compound in our research, has been micronized with RESS resulting in particles with Ø ¼ 1.52-8.78 mm.22

The processes using scCO2 as a solvent have been modified by changing process parameters (e.g., ultrahigh pressure,23 nozzle construction,24 or by expanding the scCO2 in a liquid environment25). However, since invented, particle production using scCO2 as solvent is based on rapidly decreasing the pressure.26 Although promising also for nanoparticle production, the results have not always been satisfactory regarding particle size and product uniformity.27