Supercritical fluid technology: a promising approach in pharmaceutical research

Abstract

Supercritical fluids possess the unique properties of behaving like liquids and gases, above their critical point. Supercritical fluid technology has recently emerged as a green and novel technique for various processes such as solubility enhancement of poorly soluble drugs, plasticization of polymers, surface modification, nanosizing and nanocrystal modification, and chromatographic extraction. Research interest in this area has been fuelled because of the numerous advantages that the technology offers over the conventional methods. This work aims to review the merits, demerits, and various processes such as rapid expansion of supercritical solutions (RESS), particles from gas saturated solutions (PGSS), gas antisolvent process (GAS), supercritical antisolvent process (SAS) and polymerization induced phase separation (PIPS), that have enabled this technology to considerably raise the interest of researchers over the past two decades. An insight has been given into the numerous applications of this technology in pharmaceutical industry and the future challenges which must be appropriately dealt with to make it effective on a commercial scale.

High drug-loading nanomedicines: progress, current status, and prospects

“…182,[184][185][186] The bottom-up method involves procedures that start from molecules to NCs, such as solvent exchange, 21,[187][188][189] high-gravity-control precipitation, 188,190,191 evaporative precipitation, 192 rapid expansion of supercritical solution, 193 and supercritical antisolvent methods. 194 DNCs prepared via bottom-up methods need less energy and are smaller compared with those prepared through top-down methods. Solvent exchange is the simplest, commonest, and most cost-effective method used in laboratory experiments.…”

Dynamic and Static Characteristics of Drug Dissolution in Supercritical CO2 by Infrared Spectroscopy: Measurements of Acetaminophen Solubility in a Wide Range of State Parameters

“…diagram, at the point of (P=400, T=373K) that (as we estimate) is below the dynamic crossover (Frenkel line 20 ) for scCO 2 and at the point of (P=400, T=473K) that (as we estimate) is along the Frenkel line for scCO 2 ( see the supplementary materials, figure S1). According to the general conclusions from Ref.…”

“…According to the general conclusions from Ref. 19 the first point corresponds to a liquid-like state of scCO 2 and the second point corresponds to a gas-like state of scCO 2 . The results show a significant difference in the kinetic mechanisms of dissolution of acetaminophen in these two states of scCO 2 ; in the gas-like state the dissolution process has two steps: (i) 'fast' step when the acetaminophen concentration quickly reaches a level of up to 70-80% from the saturation and (ii) a consequent 'slow' step where the concentration slowly increases up to the saturation level.…”

“…As a consequence, scCO 2 and its mixtures with other compounds became the most widely used SCF solvents these days. 4,9 scCO2-based methods allow one an effective control of particle size and polymorphism 1,2,4 and in pharmaceutical industry the use of scCO 2 is a promising alternative to standard techniques for extraction, drying and crystallization that use environmentally hazardous solvents such as acetone, carbon tetrachloride, dimethyl sulfoxide, etc. Indeed, using scCO2 in pharmaceutical applications can help to solve at least two challenging problems: (i) expensive cleanup and ecologically-friendly utilization of solvents; (ii) eliminating the traces of solvents in the final product that might still remain there in a small, but still a dangerous concentration.…”

“…In addition, scCO 2 can be used as anti-solvent to precipitate the formed crystalline phase. In the present study we use the vibration infrared spectroscopy method to investigate solubility properties of bioactive substances in scCO 2 . We show that with proper calibration it is possible to use this technique as an express-diagnostics method for determining solubility.…”