Supercritical Fluid Manufacture
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
A supercritical fluid (SCF) process for particles production was first reported in Hannay and Hogarth (1879). In spite of this fact, it was only within the last four decades that supercritical fluid techniques were systematically investigated for micronization of pharmaceuticals, natural substances, pigments, (bio)polymers, superconductor precursors, among others (Tong et al. 2001, Shariati and Peters 2003, Reverchon 1999). Different SCF techniques have been proposed taking advantage of the peculiar properties of the supercritical solvent, particularly supercritical carbon dioxide (scCO2) (Brunner 2004). The SCF is defined as a fluid that is above its critical temperature (TC) and pressure (pC), being CO2 the most common one due to its relatively low critical temperature (31.18°C) and mild critical pressure (7.4 MPa). Feature properties of a SCF are the liquid-like densities, the gas-like transport properties, and the continuous adjustable solvent power by fine tuning the temperature and pressure. Taking advantage of these properties, several SCF-based techniques have been developed for particle generation overcoming technical and environmental problems associated to the conventional ones (Türk 2014).
Black Cumin: A Review of Phytochemistry, Antioxidant Potential, Extraction Techniques, and Therapeutic Perspectives
Megh R. Goyal, Durgesh Nandini Chauhan in Plant- and Marine-Based Phytochemicals for Human Health, 2018
SFE technique is an effective and convenient alternative to conventional methods of extracting active components due to numerous benefits, for example, the use of environment-friendly and compatible fluids, such as CO2, lesser use of solvent compared to conventional methods, extraction environment is oxygen free so reduces the chance of oxidation, and the removal of the solute from solvent is easy by simple expansion and short extraction time.138 A fluid is called a supercritical fluid when its pressure and temperature reach thermodynamically above its critical point. Supercritical fluids have distinct properties of both gases and liquids as these diffuse and effuse like gases, while it possesses solubilization characteristic of liquids.161 Furthermore, the density of supercritical fluids can be modified significantly by making minute changes in pressure and temperature. Supercritical carbon dioxide has been used to extract essential oils, fatty acids, and bioactive compounds from various fruits, vegetables, and spices.54
Aromatic Medicine
Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam in Herbal Product Development, 2020
There are five intentions in picking supercritical carbon dioxide as the extraction medium: It has a basic temperature of 31 ºC; this implies extractions can be led at temperatures that are low enough not to harm the physicochemical properties of the extract.It is dormant in nature; in this manner, there is no danger of side responses, for example, oxidation.It is nontoxic; carbon dioxide is an innocuous material that is frequently utilized in beverages. It has been acknowledged by most European food and drugs acts as an extraction medium for the isolation of food related compounds.It has a low polarity; the extremity of carbon dioxide is near that of pentane and hexane, which are solvents commonly utilized in fluid extraction procedures. In this manner, a comparative scope of mixes can be extricated utilizing both techniques.It permits fractionated separation; by basically picking distinctive temperature and weight conditions for various consecutive separator vessels, a fractionated separation of the organic compounds can be achieved.
Application of scCO2 technology for preparing CoQ10 solid dispersion and SFC-MS/MS for analyzing in vivo bioavailability
Published in Drug Development and Industrial Pharmacy, 2018
Rujie Yang, Yingchao Li, Jing Li, Cuiru Liu, Ping Du, Tianhong Zhang
The 90 min dissolution results of CoQ10-SD under various reaction pressure, temperature, and reaction time are displayed in Figure 2(b–d). The results indicated that the dissolution rate was enhanced as the increasing of pressure and temperature. For the reaction time, the drug dissolution of 1 h was higher than that of 0.5 h, and was close to that of 2 h. However, the dissolution of 25 MPa was similar to 20 MPa and the temperature of 45 °C was higher than 35 and 40 °C. The pressure and temperature can affect the diffusivity and viscosity of supercritical carbon dioxide. The supercritical temperature of carbon dioxide is 304 K, and the supercritical pressure is 7.4 MPa. When the pressure and temperature reach up to the critical points, the scCO2 has density similar to a liquid, allowing the molecules to move freely and collide with the drug particles more frequently. With increasing pressure, the density increases at constant temperature, and with increasing temperature, the density decreases at fixed pressure [35]. The higher density allows carbon dioxide molecules to penetrate into the drug particles [36]. However, the temperature of 45 °C was the best choice in our study possibly because 45 °C was the most close to the melting point of CoQ10 (49 °C). Therefore, 20 MPa, 45 °C, and 1 h were chosen for the optimized reaction conditions. The design of the optimized formulation is listed in Table 2.
An expert opinion on respiratory delivery of high dose powders for lung infections
Published in Expert Opinion on Drug Delivery, 2022
Bishal Raj Adhikari, Jack Dummer, Keith C. Gordon, Shyamal C. Das
Another crystallization technique that can be used to produce inhalable particles is the supercritical fluid technique. When a liquid or gaseous substance is exposed to high temperature and pressure, it exhibits properties of both liquid and gas and is commonly referred to as supercritical fluid [61]. The temperature and pressure above which the fluid starts to show such behavior is called the critical point. For example, critical temperature and pressure for supercritical carbon dioxide (CO2) are 31.1 °C and 7.38 MPa, respectively. This fluid has the potential to be a green alternative to the use of organic solvents as it is inert and non-toxic [62]. In this technique, the drug of interest is dissolved in a solvent or supercritical fluid and crystallization can be brought about by modulating temperature/pressure or adding antisolvent or supercritical fluid [61,63]. This technique has been mainly explored to produce low dose dry powder. For example, carrier-free dry powder of budesonide prepared using acetone and supercritical CO2 (antisolvent) showed an FPF of 33% when measured using an impactor and Clickhaler® [64]. This technique has unexplored potential for high dose inhalable formulations.
Ternary solid dispersions: classification and formulation considerations
Published in Drug Development and Industrial Pharmacy, 2021
Shambhavi Borde, Sagar Kumar Paul, Harsh Chauhan
The supercritical fluid method generally uses supercritical carbon dioxide (SC-CO2) as a solubilizing solvent or anti-solvent. SC-CO2 has been widely used due to its nontoxic, inflammable nature as well as its relatively lower critical points (critical pressure =7.38 MPa, critical temperature =31.1 °C). SC-CO2 is considered as an alternative green solvent to conventional organic solvents [110]. When using SC-CO2 as a solvent, the components are dissolved in SC-CO2 and sprayed through a nozzle into an expansion vessel. In contrast, SC-CO2 as antisolvent leads to the precipitation of components as solid dispersion particles, which were initially dissolved in the organic solvent. This method has some distinct features of operating at lower temperatures to avoid heat decomposition, lower residual organic solvent, and one-step production of powders with better flowability, which makes it a promising method to prepare solid dispersions. Yin et al. reported the preparation of itraconazole TSD (D-P-P), which showed no weight loss due to residual solvent in thermogravimetric analysis and also mentioned that through the manipulation of the working conditions of pressure, temperature, solution concentration, and flow rate in the nozzle, it was possible to control the size, shape, and morphology of the products [44]. Other researchers have also used this method for preparing the D–P–P type of TSDs [33,110].
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