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Supercritical carbon dioxide extraction of cannabinoids from Cannabis sativa L. plant material
Abstract
Cannabis sativa L. extracts with high concentration of Δ⁹-tetrahydrocannabinolic acid (THCA) and Δ⁹-tetrahydrocannabinol (THC) were obtained by supercritical carbon dioxide (CO2) extraction. The objective of this work was to investigate the cannabinoid concentration of the extracts, the overall process yield under different extraction conditions, and the effect of ethanol as co-solvent. Extraction experiments were carried out with multistage pressure increments and at constant pressure of 17, 24 and 34 MPa and 328 K with flow rate of 200 g/min of CO2. At 34 MPa apparent solubilities of extracts were determined for four different Cannabis sativa L. strains with variable cannabinoids initial content. Extraction yield was highly dependent on pressure and plant material starting composition. The use of ethanol as a co-solvent was investigated with two different approaches, i.e. constant co-solvent flow, and by applying pulses of ethanol at different times though the extraction procedure. The obtained extracts were fractionated in 3 separators in a cascade configuration of decreasing temperature and pressure. The cannabinoid composition of the extracts was determined with HPLC analysis. Process extraction efficiency as high as 92% was achieved.
... 24 The extraction process for producing different types of concentrates depends on the ability of cannabinoids and other molecules of interest to dissolve in the organic solvents, including hydrocarbons and alcohols. 25 Organic solvents are generally used for cannabis extraction due to the lipophilic nature of the majority of cannabinoids. 23 While solvents such as methanol, ethanol, chloroform, butane, and hexane are commonly used, safety is a concern due to the possibility of toxicity and flammability. ...
... 23 While solvents such as methanol, ethanol, chloroform, butane, and hexane are commonly used, safety is a concern due to the possibility of toxicity and flammability. 25,26 Green solvents, including deep eutectic solvents, gas-expanded liquids, and supercritical carbon dioxide, pose low toxicity and less environmental impact than organic solvents, but extraction efficiency, preparation, and economic considerations should be taken into account. 27 Extraction temperature additionally influences extraction yield and cannabinoid and terpene concentrations. ...
... Rovetto and Aieta et al. 25 conducted a study to analyze THC extraction using a combination of supercritical CO 2 with ethanol and noticed a higher concentration of THC in the extracts compared to using supercritical CO 2 alone, without . Bars with the same first letter are not significantly (p > 0.05) different between the particle sizes for the same extraction temperature and solvent type. ...
... In addition, high-pressure technologies, such as pressurized liquid extraction (PLE) and SFE, also have been largely employed. PLE was used largely to obtain cannabinoids [47][48][49]; meanwhile, SFE is the most applied method to obtain oil [50][51][52][53][54], cannabinoids [55][56][57][58][59][60][61][62], volatile compounds [59,63,64], and phenolic compounds [46]. ...
... Many strategies for recovering compounds with supercritical fluids from cannabis were studied, such as batch extraction under fixed operational conditions [70,[79][80][81], sequential extraction process under different operational conditions (mainly temperature and pressure) in the same batch [82], extraction followed by fractionation [58,62,83], the use of co-solvents (ethanol) [58,60,81,[83][84][85], in addition to performing the decarboxylation process inside the pressure vessel before SFE [58]. The process strategy and operating conditions determine the characteristics of the extracts, such as the extraction yield, recovery of compounds, and extract's purity and composition, in addition to being related to technological aspects, such as solvent consumption, process time, among others. ...
... Regarding the operation pressure, at a fixed temperature, there is generally an increase in the recovery of cannabinoids (mass of an specific cannabidinol/mass of sample) with increasing pressure. Pressure positively influences the recovery of cannabinoids [62,85], although lower selectivities (mass of an specific cannabidinol/mass of extract) were recorded. Drinić, Vladic, Koren, Zeremski, Stojanov, Tomić and Vidović [55] found that an increase in pressure decreased the content of cannabinoids in the SFE extracts from aerial parts of Cannabis sativa (cultivar Helena). ...
Supercritical carbon dioxide (CO2) extraction techniques meet all-new consumer market demands for health-promoting phytochemical compound-rich extracts produced from green and sustainable technology. In this regard, this review is dedicated to discussing is the promise of integrating high-pressure CO2 technologies into the Cannabis sativa L. processing chain to valorize its valuable pharmaceutical properties and food biomass. To do this, the cannabis plant, cannabinoids, and endocannabinoid system were reviewed to understand their therapeutic and side effects. The supercritical fluid extraction (SFE) technique was presented as a smart alternative to producing cannabis bioproducts. The impact of SFE operating conditions on cannabis compound extraction was examined for aerial parts (inflorescences, stems, and leaves), seeds, and byproducts. Furthermore, the opportunities of using non-thermal supercritical CO2 processing on cannabis biomass were addressed for industrial hemp valorization, focusing on its biorefinery to simultaneously produce cannabidiol and new ingredients for food applications as plant-based products.
... In supercritical extraction with an average consumption of 19 kg CO 2 kg − 1 hemp, the yield was (16 ± 2) % at 40 • C and (15 ± 3) % at 60 • C; so, no important improvement with temperature was found. Similar results were claimed (Rovetto and Aieta, 2017) after the scCO 2 extraction from hemp at 34 MPa at 40 • C and 60 • C, who found no conclusive differences between the yields achieved at both temperatures. Table 3 shows basic calculations of the energy demand of all extraction technologies. ...
... The extraction at both temperatures and same moisture, resulted in a close yield, showing that the temperature in hemp extraction did not have much influence at the used pressure of 32 MPa. Similar findings were reported (Rovetto and Aieta, 2017) at 34 MPa. As can be seen in Fig. 4, at both temperatures, the maximum was reached at 20 % of moisture added (total of ~ 25 %). ...
There is great interest in hemp cultivation to obtain an oil rich in cannabinoids. Cannabidiol (CBD) is the most sought after because it has remarkable medicinal properties. But hemp crops are sometimes improperly dried, leading to excessive bacteria and moulds growth during storage, which jeopardizes the microbiological quality of the oil. As a result, the crop must be discarded with a large economic impact. In this work, the microbial load of hemp and the obtained cannabinoid rich oil was assessed after extractions using supercritical CO2 and with three ethanol-based techniques (maceration, ultrasound, Soxhlet). Extremely high bioburden was found in the hemp, much of it sporulated forms that were difficult to inactivate. The microbial load of the exhausted hemp varied significantly depending on the extraction method, with ethanolic techniques achieving the highest reduction, while supercritical CO₂ ensured the complete elimination of fungi and enterobacteria. A clear relationship was found between higher hemp moisture and increased microbial inactivation during scCO2 extraction. Fortunately, all extraction techniques yielded sterile extracts. Further, the concentration of cannabinoids, chlorophylls and polyphenols, and the antioxidant capacity of the extracts were evaluated to determine if excessive moisture in the hemp negatively impacted the composition of the oil. On the contrary, the extracts were enriched in cannabinoids. Interestingly, the most concentrated oil (74 % total cannabinoids) was obtained from wet hemp by supercritical extraction. During this latter technique, part of the hemp moisture was removed, and the exhausted hemp was solvent-free, easing its future valorisation. Based on production costs, supercritical extraction was more profitable. Consequently, this work demonstrates that wet, highly biocontaminated hemp could still be a valuable raw material, and that supercritical extraction is the best technique to obtain a CBD oil of high quality from it.
... Both, TCH and CBD are mainly produced by thermal decarboxylation of the corresponding acid forms present in the plant or the extracts, namely Δ 9 -tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). In addition to these, other phytocannabinoids have gained attention such as cannabichromene (CBC), cannabigerol (CBG) and cannabinol (CBN) [7], and their selective extraction has also become a topic of active interest [8][9][10][11]. ...
... K and 73.8 bar, but commercial CO 2 is generally supplied as a compressed liquid in cylinders at room temperature and 57.4 bar [18]. Then, the first stage of the SFE process involves the mixing of liquid CO 2 and the co-solvent (generally ethanol), the compression of the mixture up to 100-200 bar and a pre-heating up to the specified extraction temperature (323-353 K) [10,19]. Both streams can also be compressed and heated independently before mixing. ...
The change in the existing regulations in different countries regarding cannabis crops management and trading has enabled the commercial exploitation of the plant parts and of their extracts, metabolites and derivatives. Industrially, key metabolites such as cannabinoids and terpenoids are commonly extracted from the flowers by using supercritical CO2. However, supercritical units require an extremely high capital investment even at low production capacities becoming a main drawback for exploratory and de-risking research stages. In this direction, this works aims to assess a low-cost CO2 supercritical extraction technique for exploratory experiments employing solid CO2 (known as dry ice) within a high-pressure vessel. By heating the solid CO2 within the vessel, supercritical conditions can be achieved enabling extraction and recovery of the extract by subsequent depressurization. P-V-T curves were experimentally obtained to determine the required dry ice loadings to achieve specific supercritical conditions. Evaluated ranges corresponded to temperatures in-between 291-365 K, specific molar volumes of 47-90 mL/mol and the corresponding pressures ranging between 54 to 300 bar. Subsequently, the developed technique was validated in the lab-scale for the supercritical extraction of cannabis sativa threshing residues at CO2 loadings of 0.63-0.73 g/mL, temperatures between 313-343 K and the corresponding pressures of 91-176 bar. The proposed technique enabled extraction yields of 3.9-6% wt. with respect to dry biomass, with cannabinoids contents in extracts of 191.86 mg/g for CBD and 28.48 mg/g for THC. Results were comparable with those obtained in commercial supercritical equipment.
... As shown in Fig. 6, supercritical fluid extraction is a novel, eco-sustainable process that uses homogeneous solvent(s) created at temperatures and pressures above their critical points, where liquid and gas phases become indistinguishable, to extract the constituents of interest from the plant material [49,[73][74][75][76][77][78][79][80][81]. These types of supercritical homogeneous solvents which are non-condensable at temperatures and pressures above their critical point, can diffuse through solids like a gas and dissolve materials like a liquid, among others (hexane, nitrous oxides, sulfur hexafluoride, trifluoromethane toluene, pentane etc.). ...
... These types of supercritical homogeneous solvents which are non-condensable at temperatures and pressures above their critical point, can diffuse through solids like a gas and dissolve materials like a liquid, among others (hexane, nitrous oxides, sulfur hexafluoride, trifluoromethane toluene, pentane etc.). The most commonly employed supercritical solvent is CO 2 due to its numerous physiochemical qualities, heat transfer characteristics, thermodynamical profile, harmless reputation, nobleness, non-corrosiveness, colourlessness, inodorousness, inexpensiveness, inflammability and eco-benign demeanor [19, 73,76,77,[82][83][84][85][86][87][88][89][90][91][92]. CO 2 with its critical temperature (32 °C) and pressure (74 bar) can also be explored with co-solvents such as methanol, and water (subcritical fluid) in order to accelerate effusion rate, shorten extraction time and enable modulation of CO 2 non-polarity profile for effective extraction of polar compounds like the non-polar compounds [19,49,[92][93][94]. ...
Due to the perceived link between sugar and diseases such as diabetes, obesity, and cardiovascular diseases, the market for low-calorific sugar alternatives or sweeteners has intensified in recent times. Stevia (Stevia rebaudiana Bertoni) is an herbaceous perennial shrub and a member of the Asteraceae family. Stevia has found use as an alternative sugar product in beverages and other foods due to its low cost, low calorific content, and health benefits. This study is a review of various technologies that have been employed by various researchers in the processing of stevia leaves into syrup, powder, or crystals. The merits and demerits of each technology for the extraction process were also discussed. It was observed that its leaves contain the highest concentration of sweeteners and that solvent extraction is the most widely adopted extraction technique by various researchers, which has been reported to give a stevioside yield of more than 90%. The use of green-assisted extraction techniques, such as supercritical fluid extraction, ultrasonic-assisted extraction, microwave-assisted extraction, pressurized fluid extraction, and enzyme-assisted extraction, offers a higher yield, better recovery, and higher purity of the steviosides. However, these technologies are yet to be utilized on an industrial scale. Post-extraction technologies such as chromatography have been reported to give an extract purity of about 97%. Other post-extraction technologies include adsorption and membrane technology for purification and/or concentration of the extract. The study also identified potential knowledge gaps that might help drive future research in the field.
... Considering Morocco is irregularly known for cannabis plant farming despite the law promulgated in 1956, however, the Moroccan government in 2021, tends to legalize the use of cannabis plants for therapeutic, cosmetic, and industrial purposes [14] . Cannabis or marijuana belongs to the Cannabaceae family [15] , also known by the richness of the cannabis inflorescences in secondary metabolites, Cannabinoids (cannabidiol (CBD) and 9-tetrahydrocannabinol (THC)) and terpenes are two primary classes recognized as therapeutically useful active compounds [16][17][18][19][20][21] . Previous research has shown that medicinal cannabis can be used to treat a variety of conditions, including sleep difficulties, nausea, anorexia, emesis, pain, inflammation, neurodegenerative diseases, epilepsy, and cancer [22][23][24][25][26][27][28][29][30] , and others showed the potency of some cannabis plant constituents to inhibit alpha amylase activity [31] . ...
... The studied data set was formed from recent literature when focused on the phytochemicals of the cannabis plant considering their therapeutical uses [16][17][18][19][20][21] . All 3D structures of 49 studied compounds were obtained from PubChem available in the National Library of Medicine [32] , and optimized under the MMFF94 force-field with the steepest Descent algorithm using Avogadro program, then saved as PDB format files. ...
Diabetes Mellitus is one of the deadliest diseases in the world, while the current medications against this disease like acarbose represent many side effects such as diarrhea and abdominal discomfort. Many studies based on natural plants used in traditional medicine were performed to find or invent new drugs to treat diabetes mellitus disease. The traditional drug design based on the synthesis and analysis of compounds wanted to study expenses a lot of time and the cost of the synthesis process, while we can resolve these problems by using computational methods that help us to predict the efficacity, stability, and pharmacokinetics properties as a main step in the drugs design chain. In this study, the virtual screening was performed on a set of 49 compounds extracted from cannabis plants by using molecular docking simulation to examine their ability to create a stable complex with the alpha-amylase inhibitor which reduces blood glucose levels in the human body. Acarbose, a widely used anti-alpha amylase activity, was employed as a reference medicine. Further, the selected compounds which showed good binding affinity were subjected to the ADMET screening to predict the pharmacokinetics properties, Additionally, molecular dynamics testing was done to confirm the outcomes. The result was that 50 compounds docked in the binding site of the alpha-amylase protein, and 25 of those compounds demonstrated the ability to create a stable complex with the target. While the ADMET analysis indicated that two substances amongst would have favorable oral bioavailability and pharmacokinetics characteristics.
... Greater temperatures increase the risk of denaturing terpenes and increase waxes and resins, which decrease the overall extract quality. It may be possible that applying pulses of ethanol (co-solvent) improves the extraction speed with low consumption of the co-solvent and CO 2 in strains of C. sativa L. with a low concentration of cannabinoids [41]. ...
... In agreement with the extraction techniques used in Latin America, Cannabis sativa L. extracts with a high concentration of ∆ 9 -tetrahydrocannabinolic acid (THCA) and ∆ 9 -tetrahydrocannabinol (THC) were obtained by supercritical carbon dioxide (SC-CO 2 ) extraction in Argentina. The extraction yield was highly dependent on the pressure and raw material quality composition, and a process extraction efficiency as high as 92% was achieved [41]. ...
The Cannabis genus of plants has been widely used in different cultures for various purposes. It is separated into three main species: sativa, indica, and ruderalis. In ancient practices, the plant was used as a multipurpose crop and valued for its fiber, food, and medicinal uses. Since methodologies for the extraction, processing, and identification of components have become available, medical, and food applications have been increasing, allowing potential development in the pharmaceutical and healthy functional food industries. Although the growing legalization and adoption of cannabis for the treatment of diseases are key factors pushing the growth of its market, the biggest challenge is to obtain higher-quality products in a time- and cost-effective fashion, making the process of extraction and separation an essential step. Latin American countries exhibit great knowledge of extraction technologies; nevertheless, it is still necessary to verify whether production costs are economically profitable. In addition, there has been an increase in commercial cannabis products that may or may not be allowed, with or without quality fact sheets, which can pose health risks. Hence, legalization is mandatory and urgent for the rest of Latin American countries. In this article, the phytochemical compounds (cannabinoids, terpenes, and phenolic compounds), the current status of legalization, extraction techniques, and research advances in cannabis in Latin America are reviewed.
... In their study, they highlighted the use of low-temperature conditions and optimized backpressure to ensure the stability of cannabinoids throughout the analysis process. Furthermore, the ability to optimize parameters such as pressure, temperature, and co-solvent composition ensures precise control over separation conditions, making SFC a highly adaptable technique for complex matrices and diverse applications [38]. Recent advancements in SFC have focused on improving its versatility and efficiency, allowing for the separation of a broader range of analytes [39], including polar and non-polar compounds [40,41], with high precision. ...
Green analytical chemistry represents a transformative approach to analytical science, emphasizing sustainability and environmental stewardship while maintaining high standards of accuracy and precision. This review highlights recent innovations in green analytical chemistry, including the use of green solvents, such as water, supercritical carbon dioxide, ionic liquids, and bio-based alternatives, as well as energy-efficient techniques like microwave-assisted, ultrasound-assisted, and photo-induced processes. Advances in green instrumentation, including miniaturized and portable devices, and the integration of automation and chemometric tools, have further enhanced efficiency and reduced the environmental footprint of analytical workflows. Despite these advancements, challenges remain, including the need to balance analytical performance with eco-friendliness and the lack of global standards to measure and promote sustainable practices consistently. However, the future of green analytical chemistry looks promising, with emerging technologies like artificial intelligence and digital tools offering new ways to optimize workflows, minimize waste, and streamline analytical processes. By focusing on these areas, green analytical chemistry is transforming analytical methodologies into tools that not only achieve high performance but also align with global sustainability goals. This review underscores how green analytical chemistry is more than just a scientific discipline, but a pathway for reducing the ecological impact of analytical processes while driving innovation in science and industry. With the continued commitment to research, collaboration, and the adoption of cutting-edge technologies, green analytical chemistry has the potential to shape a greener and more sustainable future for analytical chemistry and its diverse applications.
... In ScCO 2 method, lipids are split by CO 2 in a supercritical state (between gas and liquid), promoting the extraction of active ingredients with high fidelity [13]. Comparisons of how the content differs between oils obtained via CP and ScCO 2 methods have been reported in previous studies [14,15]. The seeds of Cannabis sativa L., the most common nondrug type known to many people around the world as hemp, are already valuable for human nutrition and have been used globally for thousands of years. ...
Objective
This study aims to evaluate the effects of hemp seed oil (HSO) on adipose-derived stem cells (ASCs) to enhance tissue repair, regulate inflammation, and promote angiogenesis.
Background
HSO, rich in bioactive compounds, was obtained via cold press (CP) and supercritical carbon dioxide (ScCO 2 ) methods to assess its effects on cytokines and vascular endothelial growth factor (VEGF) in ASCs.
Methods
Chemical composition were assessed via gas chromatography-mass spectrometry (GC–MS) and antioxidant activity was determined by measuring the % radical scavenging activity (RSA) with 1,1-diphenyl-2-picrylhydrazyl (DPPH). ASCs were treated with HSO and, cell viability was measured at 24, 48, and 72 h using the methyl thiazolyl tetrazolium (MTT). Gene expression of interleukin-6 (IL-6), interleukin-10 (IL-10), and VEGF was quantified by real-time PCR.
Results
The CP-fixed HSO had higher linoleic (48.48%) and oleic acid (29.33%) content than ScCO 2 -extracted HSO. Phenolic content and antioxidant activity were greater in CP-fixed HSO [57.85 mgGAE (mgGallic Acid Equivalent)/g, 68.8%] than in ScCO 2- extracted HSO (58.5 mgGAE/g, 19.9%). Cell viability increased significantly with 75 and 100 µL of CP-fixed HSO at 48 and 72 h (p < 0.05). CP-fixed HSO up-regulated IL-10 and reduced IL-6 at 24 and 48 h (p < 0.05), while also increasing VEGF with 50 and 100 µL at 24 and 48 h (p < 0.05). ScCO 2 -extracted HSO primarily up-regulated IL-10 but had limited effects on IL-6 and VEGF.
Conclusions
CP-fixed HSO had superior phenolic content, antioxidant activity, and enhanced ASC viability, anti-inflammatory effects, and angiogenesis, suggesting strong therapeutic potential for stem cell use.
... For example, the inflorescence is trimmed manually or using bucking machines, and the trimmed flowers are dried after harvesting from the female plants. The particle size of the dried flowers is reduced by milling, and the shredded biomass is conveyed to the extraction unit (Rovetto and Aieta 2017). Extraction is the most important step in CBD production as it significantly impacts the product's market value. ...
Cannabidiol (CBD) in industrial hemp is a promising functional food ingredient with multifarious health benefits, including anticancer activity, antioxidant activity, anti-inflammatory properties, and anxiolytic effects. In recent years, the application of CBD in the food industry has been emerging and several CBD fortified products are available across the globe. Currently, the scientific information associated with CBD are segregated, and there is a lack of connectivity between their recent explorations. Therefore, in this review, the findings associated with CBD that are crucial for extending its food applications are comprehensively discussed. It begins by exploring the global regulatory landscape of CBD. Followingly, the factors that affect CBD production in the field, CBD isolation techniques from industrial hemp flowers, and their functional properties are comprehensively detailed. Importantly, this review examines reported delivery systems for enhancing the physicochemical properties and bioavailability of CBD, thus broadening its potential applications in the food industry. Overall, this review would connect the patches of CBD information available from the field to food and would be resourceful for food scientists, regulatory agencies, and hemp farmers.
... This method is a more efficient and green extraction compared to the traditional method, and it also supplies significant savings in terms of time, cost, and energy. In Rovetto et al., 2017 andAizpurua-Olaizola et al., 2014 the extracts obtained by supercritical fluid extraction by HPLC-MS/MS and ultrahigh performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) methods were successfully obtained and measured. Nearly 30 types of cannabinoids (cannabidiol, cannabigerol, tetrahydrocannabinol, tetrahydrocannabinolic acid), optimized by quantitative isolation, were obtained and measured from this plant extract. ...
... Existem dezenas de métodos de extração [18,32] , sendo os principais: extração hidroalcóolica [33] ; extração em fluído supercrítico [34,35] ; extração em líquido pressurizado [35] ; e prensagem a quente [32] . ...
A planta Cannabis sativa L. possui mais de 500 compostos, incluindo fitocanabinoides e outros metabólitos secundários (e.g. terpenos, alcalóides e flavonóides), sendo o Δ9-tetrahidrocanabinol (Δ9-THC) e canabidiol (CBD) os principais constituintes dos produtos de cannabis. O desafio proposto pela Cannabis sativa L. para a farmácia contemporânea está em elaborar uma cadeia produtiva efetiva,capaz de avaliar quais os melhores métodos a serem utilizados nos processos de extração, separação e purificação dos princípios ativos considerando a formulação desejada no produto final. O objetivo desse estudo é introduzir os principais métodos de obtenção de fitocanabinoides, abordando as duas primeiras etapas da produção pós-cultivo: os métodos de extração e os métodos de separação e purificação. Os métodos de extração apresentados são a hidroalcóolica (pelo seu alto rendimento e praticidade),a em fluído supercrítico (pela variedade de metabólitos secundários obtidos e efetividade em climas frios), aem líquido pressurizado (pelo ganho de rendimento em relação às extrações realizadas em pressão atmosférica) e a prensagem a quente (pela variedade de metabólitos secundários obtidos e praticidade em climas quentes). Para separação e purificação dos extratos obtidos, temos a extração de fase sólida (método simples e de baixo investimento inicial), a cromatografia de partição centrifugada (método de alto investimento inicial, porém, prático e com baixo custo de realização de processo) e cromatografia líquida de alta eficiência preparatória (método de alto investimento inicial e alto custo de processo, porém, com maior poder de separação dos componentes). A escolha dos métodos é fundamental para a eficiência da produção.
... It is important to note that this study provides evidence of unique cannabinoid and terpene profiles obtained through the three different extraction techniques at discreet conditions, and thus it is reasonable to assume that altering various parameters of an extraction protocol may yield further modification of the phytochemical profile obtained. Several studies have evaluated the efficiency of SFE extraction under varying conditions of pressure, temperature, and solvent consumption; however, results are also dependent on the specific cultivar [43][44][45]. Increasing the total amount of plant material and minimizing the storage time may likely result in higher yields and possibly more diversity in terpenes and cannabinoids for the specific hemp cultivar. Additionally, modification of the ethanol extraction process may also lead to differences in extract composition. ...
A variety of techniques have been developed to extract hemp phytochemicals for research and consumption. Some of the most common processes in the industry include supercritical CO2 extraction, hydrodistillation, and solvent-based (ethanol) extractions. Each of these processes has the potential to differentially extract various phytochemicals, which would impact their efficacy, tolerability, and safety. However, despite these differences, there has been no direct comparison of the methods and the resulting phytochemical composition. This work aimed to compare cannabinoid and terpene profiles using the three primary commercial procedures, using hemp inflorescence from a CBD/CBG dominant Cannabis sativa L. cultivar. Extracts were then evaluated for their terpene and cannabinoid content using GC-MS and LC-MS/MS, respectively. Hydrodistilled extracts contained the most variety and abundance of terpenes with β-caryophyllene to be the most concentrated terpene (25–42 mg/g). Supercritical CO2 extracts displayed a minimal variety of terpenes, but the most variety and abundance of cannabinoids with CBD ranging from 12.8–20.6 mg/g. Ethanol extracts contained the most acidic cannabinoids with 3.2–4.1 mg/g of CBDA along with minor terpene levels. The resulting extracts demonstrated substantially different chemical profiles and highlight how the process used to extract hemp can play a large role in product composition and potential biological effects.
... This method is a more efficient and green extraction compared to the traditional method, and it also supplies significant savings in terms of time, cost, and energy. In Rovetto et al., 2017 andAizpurua-Olaizola et al., 2014 the extracts obtained by supercritical fluid extraction by HPLC-MS/MS and ultrahigh performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) methods were successfully obtained and measured. Nearly 30 types of cannabinoids (cannabidiol, cannabigerol, tetrahydrocannabinol, tetrahydrocannabinolic acid), optimized by quantitative isolation, were obtained and measured from this plant extract. ...
MEDICINAL PLANTS USED IN THE TREATMENT OF HUNTINGTON'S DISEASE AND EXTRACTION METHODS
... This method is a more efficient and green extraction compared to the traditional method, and it also supplies significant savings in terms of time, cost, and energy. In Rovetto et al., 2017 andAizpurua-Olaizola et al., 2014 the extracts obtained by supercritical fluid extraction by HPLC-MS/MS and ultrahigh performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) methods were successfully obtained and measured. Nearly 30 types of cannabinoids (cannabidiol, cannabigerol, tetrahydrocannabinol, tetrahydrocannabinolic acid), optimized by quantitative isolation, were obtained and measured from this plant extract. ...
... Previous studies predominantly used a solvent system consisting of a 9:1 mixture of methanol and chloroform for sample preparation (Brighenti et al., 2017;De Backer et al., 2009;Gul et al., 2015;Hazekamp et al., 2004;Jin et al., 2020;Lehmann and Brenneisen, 1995;Mano-Sousa et al., 2023;McRae and Melanson, 2020;Mehmedic et al., 2010;Rovetto and Aieta, 2017;Smith and Vaughan, 1976;Stolker et al., 2004;Swift et al., 2013;Zivovinovic et al., 2018). This choice is attributed to its high capacity for extracting substantial quantities of cannabinoids such as CBD and Δ 9 -THC. ...
The solvent most commonly used to prepare cannabis inflorescence samples is a mixture of methanol and chloroform (9:1), which poses a health hazard. This study aimed to develop a solvent system that maximizes the extraction of two major cannabinoids,
cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), with superior performance to conventional solvents. The cannabinoid content was determined using high-performance liquid chromatography. The stability of these two cannabinoids in the optimal solvent system was also evaluated. The volume ratios of acetonitrile, methanol, and water were varied for extracting cannabinoids from two cannabis cultivars, Hang Kra Rog Phu Phan and Charlotte’s Angel, based on a D-optimal design. The solvent system developed in this study showed superior extraction efficiency to acetonitrile, as specified in the Thai Herbal Pharmacopoeia, and the methanol:chloroform mixture (9:1), as specified in the United Nations Office on Drugs and Crime manual. The optimal solvent system that provided the highest cannabinoid content consisted of acetonitrile, methanol, and water at a volume ratio of 0.511:0.289:0.200. This solvent system could extract 0.141% ± 0.023% of CBD and 3.255% ± 0.511% of Δ9-THC from the Hang Kra Rog Phu Phan cultivar, and 2.120% ± 0.143% of CBD and 3.813% ± 0.219% of Δ9-THC from the Charlotte’s Angel cultivar. The stability of cannabinoids in the optimal solvent system was comparable to that of the methanol:chloroform mixture (9:1) but superior to acetonitrile when stored at 4°C and −20°C for 28 days. In summary, the optimal solvent system developed in this study is less toxic than existing systems and can be valuable for extracting cannabinoids from cannabis during inflorescence sample preparation for analyzing their content.
... The properties of supercritical CO 2 exhibit liquid-like gas mass transfer, surface tension, solvent power, and gas-like low viscosity, which are considered for better extraction rates in a shorter time [47]. For the extraction of polar compounds, co-solvents such as ethanol can be used as supercritical CO 2 , which has a low polarity index [48]. The essential idea of SFE is that it behaves as a single phase, preserving both gas and liquid properties at the same time with moderate pressure and temperature. ...
The utilization of bioactive compounds from fresh produce waste, which is gaining attention in the agri-food and cosmetics industries, focuses on employing green extraction over conventional extraction methods. This emerging field addresses environmental concerns about food waste and the uses of bioactive phytochemicals for skin health. Modern green extraction methods aim to minimize the energy-intensive process and the use of harmful solvents. These techniques include ultrasound, microwave, and supercritical fluid extraction, pulsed electric field extraction, pressurized liquid extraction, and subcritical water extraction methods, which provide high efficacy in recovering bioactive phytochemicals from vegetable and root crops. The phytochemicals, such as carotenoids, polyphenols, glucosinolates, and betalains of fresh produce waste, exhibit various therapeutic properties for applications in skin health. These dietary antioxidants help to neutralize free radicals generated by UV radiation, thus preventing oxidative stress, DNA damage, and inflammation. The skin care formulations with these phytochemicals can serve as natural alternatives to synthetic antioxidants that may have toxic and carcinogenic effects. Therefore, this review aims to discuss different green extraction technologies, consumer-friendly solvents, and the beneficial skin health properties of selected phytochemicals. The review highlights recent research on major phytochemicals extracted from vegetables and root crops in relation to skin health.
... Fifty phytochemicals extracted from Cannabis sativa L. plant were selected from previous studies, through a careful selection process to be in silico investigated for their inhibitory effect against the main protease (M pro ) of SARS-CoV-2 [19][20][21][22][23][24][25][26][27]. As presented in Table S1, the selected phytochemicals contain 12 isolated cannabinoids and 38 terpenes, identified with their compound identifiers (CIDs). ...
Since the emergence of the coronavirus 2 (SARS-CoV-2), the approach taken to discover new drugs against this virus was to find reliable inhibitors of the main protease (Mpro) leading to minimize its proliferation and its complications observed in patients such as severe acute respiratory syndromes. In this regard, several works have been carried out based on this approach. In this investigation, combined computational studies were performed to examine the inhibitory performance of 12 cannabinoid-derived compounds and 38 terpene-derived compounds against SARS-CoV-2. At the beginning, a molecular docking study was done to predict the types of interactions and binding energies of each studied compound with respect to the active site of the main protease (Mpro). According to the docking results, seven compounds (THCV, CBN, Δ-9-THC, Δ-8-THC, CBC, THCA and CBCA) present high binding energies leading to strong interactions to their target protein. showed also more stable affinity energies than the reference drug, Narlaprevir. Then, the ADME-Tox (absorption, distribution, metabolism, excretion and toxicity) properties of these ligands were evaluated. As results, only one among the selected ligands showed that it could be selected as a potential anti- SARS-CoV2 candidate. Finally, the binding stability of this compound in the active site of the main protease was confirmed through molecular dynamics simulation which was carried out on a time scale ranging from 0 to 100ns.
... By the way, experimental for extraction only to analyze about particle size [3]. Other experiments study the effect of all parameters in extraction process [4]. They are no mathematical model to describe of cannabis sativa L. extraction. ...
This paper focuses on numerical modeling of cannabis extraction in supercritical fluid extraction (SFE) CO 2 process. First, two mathematical models, Sovova and Reverchon, are described. COMSOL program was used to solve numerical solution of both models. Then, verification of numerical models is shown. The extraction experiment was set up. Cannabis Savita L. oil was extracted in SFE CO 2 process. Extraction pressure and temperature conditions were 200 bars and 50 o C, respectively. Numerical model was customized for Cannabis Savita L. To improve solution accuracy, total mass transfer was fitted from experimental data. RMS was used to optimize total mass transfer coefficient. Experimental results and the proposed numerical solutions were in a good agreement.
... Comparatively, supercritical CO 2 has δ-values that depend on temperature and pressure, and they range in between 14 and 17 MPa 1/2 , which is closer to those of free fatty acids (18 MPa 1/2 ), vegetable oils (16-18 MPa 1/2 ) and fatty waxes (16-17 MPa 1/2 ) [16][17][18]. This explains the need for the commonly employed co-solvent method that uses ethanol during supercritical CO 2 extractions [12,19,20]. At the same time, the estimated δ-value for chlorophyll is around 20-21 MPa 1/2 which explains why colored extracts are obtained when performing ethanol extraction near ambient or at high temperatures. ...
Extraction of natural products using safe, selective and green solvents is of major importance for their use as ingredients in foods, beverages, cosmetics and pharmaceutical products. In the particular case of cannabis, ethanol at ambient conditions has been found to be very effective in the extraction of cannabinoids, terpenoids, and other valuable metabolites; however, it also extracts chlorophyll, vegetable oils and waxes. Alternatively, the selectivity towards cannabinoids could be increased by operating at lower temperatures. In this regard, this work focused on the cryogenic extraction of leaves and flowers of Cannabis sativa L. with ethanol. Extractions were carried out in a rotary tumbler under batch operation at different temperatures (−80°C to 20°C) and solvent:solid ratios (4:1 to 25:1 mL/g). The content of cannabinoids in samples was measured via U-HPLC under isocratic elution using a mixture of a 0.1% wt. formic acid aqueous solution and pure acetonitrile, using a diode array detector at 280 nm, and with an external standard method. Terpenes were quantified by GC using headspace injection, FID detection, and using external standards for calibration. The yields with respect to dry biomass were in-between 0.43% and 4.22% wt. The corresponding cannabinoids content with respect to dry material ranged from 0.25% to 2.67% wt., and these mainly corresponded to cannabidiol and cannabinol. The content of terpenoids was in between 0.01 and 1% wt., and the major fraction corresponded to monoterpenes d-Limonene, β-Myrcene, α-Terpinene, Terpinolene, and p-Cymene. Cryogenic extracts were characterized by a translucent aspect with minor content of coloring compounds and other impurities. Preferred operating conditions corresponded to −20°C and a solvent:solid ratio of 16:1 mL/g; under these conditions and with respect to dry biomass, the extraction yield was 3.47% wt., the cannabinoids content was 0.67% wt., and the CBD content was 0.59% wt.
... By the way, experimental for extraction only to analyze about particle size [3]. Other experiments study the effect of all parameters in extraction process [4]. They are no mathematical model to describe of cannabis sativa L. extraction. ...
This paper focuses on numerical modeling of cannabis extraction in supercritical fluid extraction (SFE) CO2 process. First, two mathematical models, Sovova and Reverchon, are described. COMSOL program was used to solve numerical solution of both models. Then, verification of numerical models is shown. The extraction experiment was set up. Cannabis Savita L. oil was extracted in SFE CO2 process. Extraction pressure and temperature conditions were 200 bars and 50oC, respectively. Numerical model was customized for Cannabis Savita L. To improve solution accuracy, total mass transfer was fitted from experimental data. RMS was used to optimize total mass transfer coefficient. Experimental results and the proposed numerical solutions were in a good agreement.
... We purchased 1 kg of dried and crushed Quebec LSD-type Cannabis flowers (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) from QCGold TECH, (Saint-André-Avellin, QC, Canada). The cannabis was stored in the dark, at room temperature. ...
Research on cannabis oil has evolved to encompass the pharmaceutical industry for the therapeutic potential of the active compounds for pathologies such as Alzheimer, auto-immune disorders, and cancer. These debilitating diseases are best treated with cannabinoids such as tetrahydrocannabinol (∆⁹⁻THC), cannabigerol (CBG), and cannabinol (CBN), which relieve neuropathic pain and stimulate the immune system. We extracted cannabinoids from plants with supercritical CO2 and produced an extract with a total yield close to 26%. The three-level Box–Behnken experimental design considered four factors: Temperature, pressure, CO2 flow rate, and processing time, with predetermined parameters at low, medium, and high levels. The mathematical model was evaluated by regression analysis. The yield of ∆⁹⁻THC and CBG reached a maximum after 2 h and 15 g/min of CO2, 235 bar, 55 °C (64.3 g THC/100 g of raw material and 4.6 g CBG/100 g of raw material). After another 2 h of extraction time, the yield of CBN reached 2.4 g/100 g. The regression analysis identified pressure and time as the only significant factors for total yield while pressure was the only significant factor for ∆⁹⁻THC and CBG. Time, temperature, pressure, and flow rate were all significant factors for CBN.
... Solvent-based extraction methods such as Soxhlet extraction [54,55], dynamic maceration [56], ultrasonic-assisted extraction [57] and pressurized liquid extraction [57][58][59] require a solvent to complete the extraction process. The solvents used to extract cannabinoids include ethanol, butane, propane, hexane, petroleum ether, methyl tertbutyl ether, diethyl ether, carbon dioxide (CO 2 ), and vegetable oils, such as olive oil [60][61][62][63]. In these methods, the solvents may become a residue in the final extract [64]. ...
There has been an increased interest of the scientific community in cannabis and its constituents for therapeutic purposes. Although it is believed that cannabinoids can be effective for a few different conditions and syndromes, there are little objective data that clearly support the use of cannabis, cannabis extracts or even cannabidiol (CBD) oil. This review aims to explore the therapeutic potential of phytocannabinoids and synthetic cannabinoids for the treatment of several diseases. A broad search covering the past five years, was performed in PubMed and ClinicalTrial.gov databases, to identify papers focusing on the use of medical phytocannabinoids in terms of tolerability, efficacy and safety. Accordingly, there are preclinical data supporting the use of phytocannabinoids and synthetic cannabinoids for the management of neurological pathologies, acute and chronical pain, cancer, psychiatric disorders and chemotherapy-induced emetic symptoms. However, regarding the clinical trials, most of the collected data do not fully support the use of cannabinoids in the treatment of such conditions. Consequently, more studies are still needed to clarify ascertain if the use of these compounds is useful in the management of different pathologies.
... Subsequently, the products are dried and stored in batches, and they can later be transferred to the extraction facility of the company itself or a different extraction facility according to the corresponding laws for extraction of cannabis by products in every country. The techniques employed for extraction include using supercritical CO 2 , ethanol or hydrocarbon in order to isolate specific desirable cannabinoid compounds [18][19][20]. ...
Digital Twins are digital equivalents of real-life objects. They allow producers to act immediately in case of (expected) deviations and to simulate effects of interventions based on real-life data. Digital Twin and eXtended Reality technologies (including Augmented Reality, Mixed Reality and Virtual Reality technologies), when coupled, are promising solutions to address the challenges of highly regulated crop production, namely the complexity of modern production environments for pharmaceutical cannabis, which are growing constantly as a result of legislative changes. Cannabis farms not only have to meet very high quality standards and regulatory requirements but also have to deal with high production and market uncertainties, including energy considerations. Thus, the main contributions of the research include an architecture design for eXtended-Reality-based Digital Twins for pharmaceutical cannabis production and a proof of concept, which was demonstrated at the Wageningen University Digital Twins conference. A convenience sampling method was used to recruit 30 participants who provided feedback on the application. The findings indicate that, despite 70% being unfamiliar with the concept, 80% of the participants were positive regarding the innovation and creativity.
Plant-derived bioactive compounds, such as polyphenols, flavonoids, alkaloids, and terpenes, exhibit diverse biological properties, making them valuable for food, nutraceutical, pharmaceutical, and cosmetic applications. The extraction process significantly impacts the yield, quality, and environmental footprint of these compounds. While traditional methods have several limitations, emerging green technologies offer efficient, sustainable alternatives. Techniques such as supercritical fluid extraction, microwave-assisted extraction, ultrasound-assisted extraction, enzyme-assisted extraction, and pressurized liquid extraction, maximize bioactive compound recovery while minimizing solvent usage, energy consumption, and thermal degradation. Advances in green solvents, including ionic liquids and deep eutectic solvents, further enhance extraction efficiency and environmental compatibility. Despite challenges like high equipment costs and process optimization, green extraction methods hold immense promise for sustainable bioactive compound extraction.
Cannabinoids, particularly cannabidiol (CBD), have been gaining attention for their numerous potential health benefits and are employed in various industries. However, there are unresolved challenges in CBD extraction including low yields, impurity issues, and environmental concerns, suggesting the requirement for green methods. Hence, our review objectives are to assess the efficacy, and the impact of novel solvents used for CBD extraction, considering green and sustainable techniques. The traditional extraction methods such as maceration and Soxhlet extraction used for CBD extraction have limitations such as low efficiency, long extraction times, high energy consumption, and substantial CO₂ emissions, raising environmental concerns. Emerging green extraction techniques, such as supercritical fluid extraction, deep eutectic solvents, and microwave-assisted extraction, offer promising alternatives by reducing solvent use, minimizing processing time, and enhancing extraction yields. Supercritical CO2 extraction, utilizing supercritical fluids' unique properties offers efficient and safe CBD extraction. Emerging green solvents such as ionic solvents and deep eutectic solvents provide promising alternatives for CBD extraction due to their properties such as no or low toxicity compared to the traditionally used solvents. Pressurized liquid extraction, such as subcritical water extraction, and techniques like microwave-assisted and ultrasonic-assisted extraction provide rapid and efficient alternatives for CBD extraction. To fulfill the growing demand for CBD extracts, future research can aim at developing efficient and sustainable extraction techniques while reducing the potential degradation of CBD, removing impurities produced during extraction, and considering concepts of sustainability and the One Health approach.
The isolation of cannabidiol (CBD) with a purity greater than 99%, while avoiding the presence of Δ9-tetrahydrocannabinol (THC), is essential for both exploring CBD applications and its commercialization. The scientific literature lacks robust and scalable protocols for obtaining pure CBD, instead primarily focusing on obtaining hemp extracts with higher cannabinoid content. Herein, we present a complete procedure for obtaining pure CBD crystals, starting from an industrial hemp cultivar. The protocol includes thermal decarboxylation of cannabinoids, supercritical CO2 extraction, winterization of the extract, CBD purification via sequential C18 reverse-phase silica filtration, silica gel chromatography, and selective crystallization. Each step has been carefully optimized to identify the best solvent, solvent/extract ratio, and silica/extract ratio to minimize CBD loss in waste fractions and to enable solvent and material recovery for recycling, aligning with a sustainable perspective. The scale-up of the procedure to 100–600 g for each step demonstrated the feasibility of our protocol for the obtainment of pure CBD crystals. An overall 52% yield of CBD with a purity exceeding 99% and a negligible THC content was achieved.
Extraction of cannabinoids from different parts of the plant matrix is often carried out by various traditional methods based on the use of organic solvents. Supercritical fluid extraction (SFE) has emerged as one of the most intriguing approaches for the extraction of cannabinoids. This review examines the importance of the SFE of cannabinoids, extraction parameters, selection of a suitable co-solvent/modifier, and appropriate sample preparation. To characterise the composition of the mixture of cannabinoids different analysis methods can be applied. One of them is high-performance liquid chromatography (HPLC), which requires no derivatisation of the analysed sample and allows for a determination of a wide variety of both acidic and neutral cannabinoids. Nevertheless, liquid chromatography with tandem mass spectrometry (LC-MS/MS) is gaining increasing importance due to its superior identification of analytes which is based on both the retention times of analytes as well as specific qualifier ions. Another interesting analytical method is supercritical fluid chromatography (SFC), which uses supercritical fluids (SCFs) such as CO2 in combination with different modifiers, to successfully separate and determine cannabinoids. The use of SFC allows for an efficient and above all, rapid separation of the desired analytes. There is an essential need to efficiently investigate the influence of various experimental parameters on the retention behaviour of cannabinoids in SFC.
Legalization of low-tetrahydrocannabinol-high-cannabidiol cannabis plants is gaining momentum due to growing demand for these products. In some countries, the testing of cannabis and products containing it is a legal requirement: cannabis is identified, the amount of tetrahydrocannabinol or cannabidiol and their precursor acids is assessed. Current research requires more sensitive and reliable analytical methods for accurate identification and quantification of cannabis components. This article purpose is to review the latest advances in the scientific literature on the isolation and analysis of cannabis and cannabis-containing products in the context of forensic science. Research methods included analysis of information on this topic using search engines, including Google, Google Scholar, Web of Science, PubMed, and ScienceDirect. Search requests took into account scientific, analytical and statistical reports in the field of forensic research. Since the forensic expert must be well-versed in modern trends in the analysis of prohibited substances and use the latest data from the analytical and forensic literature in his work, such information will help them choose research methods, taking into account the actual resources and equipment of forensic laboratories. According to the article purpose, advantages and disadvantages of existing methods of extraction and analysis of objects containing cannabis for identification, quantification, profiling and age estimation of cannabis are considered.
Natural extracts, such as those from the residues of the Olea europaea industry, offer an opportunity for use due to their richness in antioxidant compounds. These compounds can be incorporated into porous polymeric devices with huge potential for tissue engineering such as bone, cardiovascular, osteogenesis, or neural applications using supercritical CO2. For this purpose, polymeric scaffolds of biodegradable poly(lactic-co-glycolic acid) (PLGA) and chitosan, generated in situ by foaming, were employed for the supercritical impregnation of ethanolic olive leaf extract (OLE). The influence of the presence of chitosan on porosity and interconnectivity in the scaffolds, both with and without impregnated extract, was studied. The scaffolds have been characterized by X-ray computed microtomography, scanning electron microscope, measurements of impregnated load, and antioxidant capacity. The expansion factor decreased as the chitosan content rose, which also occurred when OLE was used. Pore diameters varied, reducing from 0.19 mm in pure PLGA to 0.11 mm in the two experiments with the highest chitosan levels. The connectivity was analyzed, showing that in most instances, adding chitosan doubled the average number of connections, increasing it by a factor of 2.5. An experiment was also conducted to investigate the influence of key factors in the impregnation of the extract, such as pressure (10–30 MPa), temperature (308–328 K), and polymer ratio (1:1–9:1 PLGA/chitosan). Increased pressure facilitated increased OLE loading. The scaffolds were evaluated for antioxidant activity and demonstrated substantial oxidation inhibition (up to 82.5% under optimal conditions) and remarkable potential to combat oxidative stress-induced pathologies.
Supercritical fluid extraction using CO2 is a widely recognized method for purifying oil extracts. Understanding the extraction process is important for improving yields. While most research has focused on one-dimensional simulations, there is a need for three-dimensional models that better simulate real extraction behavior. This paper focuses on a two-dimensional axisymmetric model to study the complexities of three-dimensional extraction processes. The proposed mathematical and axisymmetric model describes the extraction of cannabis using a supercritical fluid extraction (SFE) CO2 process. The COMSOL program was used to solve 2D axisymmetric and laminar flow dynamics within the extractor. The velocity was derived from the axisymmetric Navier-Stokes equation was used in the mathematical model. A 2D mathematical and axisymmetric model was developed based on 1D Reverchon models, and it was validated using experimental data. The experimental data were used to determine one unknown parameter. The total mass transfer coefficient (K) was determined from the experimental results and integrated into computational model. Creating a computational model, meshing, and conducting a 2D axisymmetric simulation analysis of Cannabis sativa L. oil extraction. The proposed curve was computed using a numerical method and was adjusted iteratively to converge with the experimental data, verified by minimizing the Root Mean Square (RMS) error. The experimental data yielded a total mass transfer coefficient (K) of 1.0194 x 10-8 m/s, which was then used in the 2D axisymmetric simulation. The results of the axisymmetric simulation show the concentration distribution within the extractor. The predictions of the proposed numerical 2D solutions closely aligned with the experimental data. The concentration of oil in the axisymmetric results is in accordance with the velocity. The model used in the supercritical fluid extraction process is ideal for purifying extractions, especially for medical and pharmaceutical purposes. This model can be further developed into more complex process and new design extractor for achieving high performance extraction. The scientific community can benefit from the model that combines the Navier-Stoke equation and extraction equation. It can be used to improve extraction simulations for other extraction methods or supercritical fluid in different fields.
The medicinal plants perform wide applications due to essential oils and biologically active constituents which are utilized in various industries. Revealed biological activity of constituents in essential oils, such as antibacterial, antioxidant, anti-inflammatory, antifungal, antitumor, antiviral, and insecticidal led to their application in the role of importance in pharmacy, cosmetic, food, and aroma industries. This review is focused on recently applied extraction techniques followed by optimization of the processes to provide the most effective potential of essential oils in the therapeutic and pharmaceutical industries. Bioactive compounds and their maintenance in the industry are gaining attention due to their features to overcome synthetic and unsafe medicaments on the global market. Thus, the widespread application of bioactive compounds of plant essential oils requires scientific investigations of their isolation, an optimization of their yields, a concise analysis of their properties, formulations, and stability. Significant research is performed on the production and characterization of essential oils with the main goal to apply them as pharmaceutical constituents, as flavors which might be used for the preparation of some food, cosmetic, and aroma.
Cannabis sativa, a versatile plant with numerous varieties, holds promising potential for a wide range of biological activity. As raw materials for research, we chose leaves and inflorescences of hemp varieties such as Białobrzeskie, Henola, and Tygra, which are cultivated mainly for their fibers or seeds. The choice of extraction is a key step in obtaining the selected compositions of active compounds from plant material. Bearing in mind the lipophilic nature of cannabinoids, we performed supercritical carbon dioxide (scCO2) extraction at 50 °C under 2000 (a) and 6000 PSI (b). The cannabinoid contents were determined with the use of the HPLC-DAD method. The antioxidant capabilities were assessed through a series of procedures, including the DPPH, ABTS, CUPRAC, and FRAP methods. The capacity to inhibit enzymes that play a role in the progression of neurodegenerative diseases, such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase was also studied. The dominant cannabinoids in the extracts were cannabidiol (CBD) and cannabidiolic acid (CBDA). The highest concentration of eight cannabinoids was detected in the Tygra inflorescences extract (b). The most notable antioxidant properties were provided by the Tygra inflorescences extract (b). Nonetheless, it was the Henola inflorescences extract (b) that demonstrated the most efficient inhibition of AChE and BChE, and tyrosinase was inhibited the most significantly by the Białobrzeskie inflorescences extract (b). Multidimensional comparative analysis enrolled all assays and revealed that the Henola inflorescences extract (b) showed the most substantial neuroprotective potential.
Δ9-Tetrahydrocannabinol and cannabidiol, which are present in cannabis extract, exhibit low bioavailability when administered orally due to significant first-pass metabolism. The use of a self-emulsifying drug delivery system (SEDDS) can enhance their dissolution and bioavailability. However, liquid SEDDS formulations are prone to inadequate stability. To address this issue, the development of a solid SEDDS formulation was explored. This study aimed to optimize directly compressible self-emulsifying tablets containing cannabis extract obtained from supercritical carbon dioxide extraction. Initially, a liquid SEDDS of cannabis extract was solidified by adsorption onto solid carriers (colloidal silicon dioxide and microcrystalline cellulose). The resulting solid mixture was then combined with other pharmaceutical excipients and compressed into tablets. Three factors were optimized using the Box-Behnken design: compressional force (1,000–2,000 psi), quantity of hydroxypropyl methylcellulose (0–6%), and quantity of croscarmellose sodium (0–6%). The results revealed that a mass ratio of colloidal silicon dioxide, microcrystalline cellulose, and liquid SEDDS of cannabis extract at 0.65:2:1 successfully solidified the mixture. The optimal tablet formulation was achieved with a compressional force of 2,000 psi, without the addition of hydroxypropyl methylcellulose or croscarmellose sodium. Verification data indicated that the predictions made by the computer software were accurate and reliable. The developed tablets exhibited improved dissolution of the cannabis extract, with Δ9-tetrahydrocannabinol demonstrating higher dissolution compared to cannabidiol. Additionally, the compressed tablets were capable of emulsifying small nano-sized droplets (approximately 200 nm). However, the droplets exhibited a larger size and broader polydispersity index compared to the liquid SEDDS. In conclusion, the study successfully developed directly compressible self-emulsifying tablets that enhanced the dissolution of cannabis extract.
Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological
effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis
Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (delta9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.
Fibre and bioactive cannabinoids are obtained naturally from cannabis. Till now, almost 144 cannabinoids have been found and more are being unveiled. Cannabinoids which are in natural or in altered forms are more exposed to light, oxygen and high temperature. The recent approval of cannabis legalisation has increased the cannabis application in the food‐processing industries. Studies regarding the safety and quality assurance of food systems of cannabis edibles are limited. Moreover, with cannabinoids, there are many other phytochemicals like flavonoids, terpenoids, lignans and polysaccharides. Within the matrix of cannabis, these polysaccharides are able to exhibit probiotic or prebiotic properties and also can improve the microbiome composition in the gut. Through the processes of metabolism and excretion, bioactive phytochemicals of cannabis especially cannabinoids can modify structurally during the enterohepatic detoxification and fermentation process of the gut. Edibles are now being used widely in food industries for consumer use. In this review, we discussed edibles in the food industry, their potential hazards regarding food safety and their future implementation. Furthermore, consumer perception and acceptance of the edibles products and the challenges involved in developing the edibles products would be discussed in detail in this article. By understanding the edibles, legislation, safety and consumers' willingness, edible food could be acceptable among worldwide consumers in the near future. image
Medicinal and recreational Cannabis sativa is a sector that has exploded in popularity both in academia and industry due to the relaxation in legislation concerning the controlled substance. This business is currently valued at $37 billion in annual sales. As cultivation of cannabis increases, waste from this sector will increase, providing a challenge, with legislative constraints of Δ9-tetrahydrocannabinol, and opportunity in sustainable management of this waste. Research into the waste management of cannabis production waste is vital as sustainability of waste management is a pressing issue and will provide opportunities for businesses to make use of said waste. This paper will use databases such as Scopus, Web of Science and Google scholar to identify literature to review related to cannabis waste and cannabis waste management systems. It has been discovered that the majority of plant biomass waste is generated during the cultivation period, with growing media being a large contributor to waste generated. Currently there are four methods for appropriate cannabis waste management, that are landfilling, composting, incineration and anaerobic digestion. Although there is this current information available further research is required to determine the most efficient method of disposal and pre-treatments, or novel approaches, to improving valorisation of this waste.
There are diverse methods to extract cannabinoids from Cannabis, including conventional and advanced techniques. In selecting the proper method, several parameters have to be considered, mainly solvents, time of extraction, temperature, pressure, size of the plant material, and matrix/solvents ratio. Basing on the current literature, the use of organic solvents is the most convenient method for cannabis extraction. Among the conventional methods, Soxhlet extraction and dynamic maceration gave the best results, even though these techniques are time-consuming and with harmful environmental impact, furnishing also low yields and low quality of extracts. For this reason, several advanced techniques have been developed, including pressurized liquid extraction, ultrasound-assisted extraction, supercritical fluid extraction, microwave-assisted extraction, enzyme-assisted extraction, pulsed electric field treatment. These are characterized by shorter extraction times, lower amounts of solvent needed, the possibility to work at lower temperatures, and higher adaptability to automation, being therefore more green and sustainable methods.
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tIn this work, hemp (Cannabis sativa L.) seed oil was produced by extraction with supercritical CO2underdifferent extraction conditions (temperature, pressure and time). The objective was to evaluate the influ-ence of extraction conditions on concentration of tocopherols, fatty acids and pigments in hemp seed oil.The composition of hemp seed oil obtained with supercritical CO2was compared with the hemp oilextracted by n-hexane using Soxhlet method and with oil obtained by pressing using screw expeller.Using supercritical CO2extraction the extracts higher in concentration of tocopherol were produced.The amount of �- tocopherol in supercritical extracts ranged from 37.09 to 110.61 mg L−1, dependingon the applied process conditions, while �-tocopherol content was significantly higher (2–3 times). Thecontent of pigments in the hemp oil obtained by supercritical CO2had been changed significantly duringthe extraction time from 9.79 to 178.76 mg kg−1for total chlorophyll content and 8.15 to 57.66 mg kg−1for total carotene content. By selecting the relevant process conditions of supercritical extraction it ispossible to obtain hemp seed oil with physical or nutritional properties of interest to the food industry.
The apparent solubility controls the initial stage of
supercritical fluid extraction of natural products, which is most important
for the process economics. Based on the literature, data on CO2 apparent solubility of volatile substances from different matrices as leaves,
flowers, rhizomes and seeds were collected and compared with their
thermodynamic solubility. The adsorption isotherm derived by del Valle and Urrego as a
modification of the isotherm proposed by Perrut et al. is universal enough to interpret these data as well as the
apparent solubility of vegetable oils from seeds, for which it was originally
proposed. When the apparent solubility of minor extract components in CO2 is compared with their thermodynamic solubility, their fraction in the
extracted mixture should be taken into account.
Objective: To determine the gene expression of antioxidant enzymes by hemp seed extracts in human hepatoma (HepG2) cells.
Methods: Ethanol and supercritical fluid (SF) extracts obtained from de-hulled hemp seed were used for the evaluation of in vitro antioxidant activity and gene expression of antioxidant enzymes. In vitro antioxidant activities of the samples evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical scavenging assays. The expression of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in HepG2 cells was evaluated by real-time PCR.
Results: In the antioxidant assay, SF extract of hemp seed exhibited higher ABTS and DPPH radical scavenging activities (IC50 of 66.6 µg/mL and 9.2 mg/mL, respectively) than ethanol extract. The results of antioxidant enzyme expression in real-time PCR study revealed the H2O2 (200 µM) challenged HepG2 cells reduced the expression of enzymes such as SOD, GPx and CAT. However, the cells treated with ethanol and SF extracts were up-regulated the expression of antioxidant enzymes in concentration dependent manner. When compared to ethanol extract, the SF extract exhibited higher activity in the expression of all the antioxidant enzymes at the concentration of 500 µg/mL.
Conclusions: In conclusion, the findings of our study demonstrated that the hemp seed effectively inhibited H2O2 mediated oxidative stress and may be useful as a therapeutic agent in preventing oxidative stress mediated diseases.
This review provides an update on the use of supercritical fluid (SCF) technology as applied to food-based materials. It advocates the use of the solubility parameter theory (SPT) for rationalizing the results obtained when employing sub- and supercritical media to food and nutrient-bearing materials and for optimizing processing conditions. Total extraction and fractionation of foodstuffs employing SCFs are compared and are illustrated by using multiple fluids and unit processes to obtain the desired food product. Some of the additional prophylactic benefits of using carbon dioxide as the processing fluid are explained and illustrated with multiple examples of commercial products produced using SCF media. I emphasize the role of SCF technology in the context of environmentally benign and sustainable processing, as well as its integration into an overall biorefinery concept. Conclusions are drawn in terms of current trends in the field and future research that is needed to secure new applications of the SCF platform as applied in food science and technology. Expected final online publication date for the Annual Review of Food Science and Technology Volume 5 is February 28, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
New model for supercritical fluid extraction (SFE) of natural products is presented. Like other models based on the concept of broken and intact cells, it is particularly suited to fit experimental data as it almost independently simulates two extraction periods, the first one governed by phase equilibrium and the second one governed by internal diffusion in particles. Its new feature is a detailed description of the first extraction period where different types of phase equilibrium and solvent flow patterns are taken into account. A simplified approximate form of the model is used to analyse its properties and to estimate its parameters. The number of model parameters is, in dependence on the complexity of the extraction process, 1–3 for phase equilibrium, 2–3 for mass transfer and 1 for flow pattern. The model is versatile, but, as a consequence, more data are necessary than a single extraction curve to determine its parameters in the first period. The evaluation of model parameters from extraction curves is shown on data sets from literature.
. A central tenet underlying the use of botanical remedies is that herbs contain many active ingredients. Primary active ingredients may be enhanced by secondary compounds, which act in beneficial syn-ergy. Other herbal constituents may mitigate the side effects of dominant active ingredients. We reviewed the literature concerning medical can-nabis and its primary active ingredient, ∆ 9 -tetrahydrocannabinol (THC). Good evidence shows that secondary compounds in cannabis may enhance the beneficial effects of THC. Other cannabinoid and non-cannabinoid compounds in herbal cannabis or its extracts may reduce THC-induced anxiety, cholinergic deficits, and immunosuppression. Cannabis terpenoids and flavonoids may also increase cerebral blood flow, enhance cortical activity, kill respiratory pathogens, and provide anti-inflammatory activ-ity. [Article copies available for a fee from The Haworth Document Delivery Service: and: Cannabis Therapeutics in HIV/AIDS (ed: Ethan Russo) The Haworth Integrative Healing Press, an imprint of The Haworth Press, Inc., 2001, pp. 103-132. Single or multiple copies of this arti-cle are available for a fee from The Haworth Document Delivery Service [1-800-342-9678, 9:00 a.m. -5:00 p.m. (EST). E-mail address: getinfo@haworthpressinc.com].
Among the different extraction techniques used at analytical and preparative scale, supercritical fluid extraction (SFE) is one of the most used. This review covers the most recent developments of SFE in different fields, such as food science, natural products, by-product recovery, pharmaceutical and environmental sciences, during the period 2007–2009. The revision is focused on the most recent advances and applications in the different areas; among them, it is remarkable the strong impact of SFE to extract high value compounds from food and natural products but also its increasing importance in areas such as heavy metals recovery, enantiomeric resolution or drug delivery systems.
The cannabis plant (Cannabis sativa L.) has a long history as a recreational drug, but also as part of traditional medicine in many cultures. Nowadays, it is used by a large number of patients worldwide, to ameliorate the symptoms of diseases varying from cancer and AIDS to multiple sclerosis and migraine. The discovery of cannabinoid-receptors and the endocannabinoid system have opened up a new and exciting field of research. But despite the pharmaceutical potential of cannabis, its classification as a narcotic drug has prevented the successful development of cannabis into modern medicine. Although a huge number of scientific papers has been published on cannabis, there is currently no scientific consensus on the usefulness of medicinal cannabis. In 2004, The Netherlands became the first country to make herbal cannabis available as a prescription drug. The phytochemical research presented in this thesis has been possible because of the availability of these high-grade cannabis plants. This thesis has a specific focus on the cannabinoids and on analytical problems that currently obstruct advanced study of the cannabis plant. Furthermore, it deals with much needed methods for quality control and with administration forms of medicinal cannabis. In general, it may be considered a general guidebook, covering all the basic phytochemical aspects of medicinal cannabis.
Cannabis sativa spp. is an exceptional multicomponent natural resource used as nutritional supplements, textiles, building materials, body care products, food, and medicines, to name a few. It has been cultivated for millennia to exploit the plant’s toolbox of useful natural compounds it offers. This chapter explores the chemical constituents responsible for the plant’s therapeutic properties and examines efficacious compounds as nutraceuticals. A qualitative and quantitative look at these components highlights important trends for both fiber-type hemp and medical C. sativa. Key aspects of C. sativa taxonomy, biology, and biochemistry are addressed. Specifically, the convergent biosynthetic pathways used by the plant to produce cannabinoids and terpenes are outlined. The biologically active components are described at a molecular level and the in vitro and in vivo data are compiled to offer quantitative insight into the mechanism of action, as well as their potential for use as nutraceuticals.
An HPLC-DAD method for the quantitative analysis of Δ(9)-tetrahydrocannabinol (THC), Δ(9)-tetrahydrocannabinolic acid-A (THCA-A), cannabidiol (CBD), and cannabinol (CBN) in confiscated cannabis products has been developed, fully validated and applied to analyse seized cannabis products. For determination of the THC content of plant material, this method combines quantitation of THCA-A, which is the inactive precursor of THC, and free THC. Plant material was dried, homogenized and extracted with methanol by ultrasonication. Chromatographic separation was achieved with a Waters Alliance 2695 HPLC equipped with a Merck LiChrospher 60 RP-Select B (5μm) precolumn and a Merck LiChroCart 125-4 LiChrospher 60 RP-Select B (5μm) analytical column. Analytes were detected and quantified using a Waters 2996 photo diode array detector. This method has been accepted by the public authorities of Switzerland (Bundesamt für Gesundheit, Federal Office of Public Health), and has been used to analyse 9092 samples since 2000. Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Two calibration ranges are used, a lower one for THC, CBN and CBD, and a higher one for THCA-A, due to its dominant presence in fresh plant material. As provider of the Swiss proficiency test, the robustness of this method has been tested over several years, and homogeneity tests even in the low calibration range (1%) show high precision (RSD≤4.3%, except CBD) and accuracy (bias≤4.1%, except CBN).
To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology, and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. Δ9-Tetrahydrocannabinol (Δ9-THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis. Cannabis and Δ9-THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of Δ9-THC limit tolerability. CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 and α1 glycine receptors. CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ9-THC medical marijuana have claimed efficacy, but studies were not controlled. CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Along more than a decade, R&D on supercritical fluid extraction (SFE) of vegetable matrices has been increasingly reported in the literature. Aiming at portraying the current state of this field and its evolution in terms of raw materials, products, modes of operation, optimization, modeling techniques, and closeness to industrial application, a large compilation of almost 600 essays from 2000 to 2013 has been deeply analyzed in order to unveil those indicators and their trends. Furthermore, strengths and weaknesses are identified, and some remarks that may drive upcoming research are provided. Globally, more than 300 species are reported in the literature, with prevalence of the extraction of seeds (28% of works) and leaves (17%). The main families of extracted compounds, cosolvents and operating conditions adopted are critically examined, being possible to conclude that researchers investigate many times working regions far from the optimum due to practical limitations or absence of experimental optimization. Current phenomenological, statistical and semi-empirical approaches are reviewed, along with scale-up studies, and economic analysis. In the whole, the most comprehensive picture over SFE of vegetable matrices is provided in this review, highlighting pertinent aspects and opportunities that may further consolidate the convincing route of this technology for the next years.
Supercritical carbon dioxide (SC-CO2) was employed to extract oil from hemp (Cannabis sativa L.) seeds. For ground seeds, the supercritical extraction was carried out at temperatures of 40, 60 and 80 °C and pressures of 300 and 400 bar. Different solvent-ratios were applied. Supercritical CO2 extractions were compared with a conventional technique, n-hexane in Soxhlet. The extraction yields, fatty acid composition of the oil and oxidation stability were determined. The seed samples used in this work contained 81% PUFAs, of which 59.6% was linoleic acid (ω-6), 3.4% γ-linolenic (ω-3), and 18% α-linolenic (ω-6). The highest oil yield from seeds was 22%, corresponding to 72% recovery, at 300 bar and 40 °C and at 400 bar and 80 °C. The highest oxidation stability corresponding to 2.16 mM Eq Vit E was obtained at 300 bar and 80 °C.
Kinetics of supercritical fluid extraction (SFE) from plants is variable due to different micro-structure of plants and their parts, different properties of extracted substances and solvents, and different flow patterns in the extractor. Variety of published mathematical models for SFE of natural products corresponds to this diversification. This study presents simplified equations of extraction curves in terms of characteristic times of four single extraction steps: internal diffusion, external mass transfer, hypothetic equilibrium extraction without mass transfer resistance, and displacement of the solution from the extractor. Preliminary evaluation of experimental extraction curves using these equations facilitates the choice of proper detailed model for SFE and enables estimation of changes in the extraction kinetics with the changes in operation conditions and extraction geometry.
Hemp seed oil is considered one of the best nutritional oil for health. The present work is focused on the optimization of the hemp seed oil extractive process at laboratory level using supercritical carbon dioxide (SC-CO2) as solvent. Response surface methodology (RSM) was used to optimize hemp seed oil extraction yield and oxidation stability. Independent variables were operating temperature (40, 50 and 60 °C), pressure (250, 300 and 350 bar) and particle diameter (0.59, 0.71 and 0.83 mm). A second-order polynomial equation was used to express both the oil yield and the oil oxidation stability as a function of independent variables. The responses and variables were fitted well to each other by multiple regressions. The maximum oil yield, 21.50% w/w, was obtained when SC-CO2 extraction was carried out at 40 °C, 300 bar and 0.71 mm of particle size. The maximum oil oxidation stability, 2.35 Eq α toc/ml oil, was obtained at 60 °C, 250 bar and 0.83 mm of particle size. A comparison between hemp seed oil composition extracted by SC-CO2 under the optimum operating conditions determined by RSM for oil yield and by organic solvent was reported.
Hemp (Cannabis sativa L.) seed oil is valued for its nutritional properties and for the health benefits associated with it. Its greatest feature is that the ratio of linoleic acid and linolenic acid is the desirable value of 3:1. In this research, supercritical carbon dioxide was applied to extraction of functional oil from hemp seed. In order to determine the effect of temperature and pressure on the yield of extracted components, the oil was extracted from hemp seed at temperatures between 40 and 80 °C, pressures of 20–40 MPa and a CO2 flow rate of 3 mL/min. The solubility of hemp seed oil in SCCO2 determined experimentally was fitted to the Chrastil equation to determine the model parameters. The solubility calculated by Chrastil equation was compared with the experimental data. Finally, the fatty acid profile of the oil was evaluated by gas chromatography-flame ionization detection (GC-FID). There are no significant differences in the compositions of five abundant fatty acid components of the oil obtained at different sampling times with SCCO2 extraction and other extraction methods.
The solubilities of two different non-psychoactive cannabinoids i.e., cannabigerol (CBG) and cannabidiol (CBD), in supercritical carbon dioxide (CO2) have been determined at 315, 326 and 334K and in the pressure range from 11.3 to 20.6MPa. These solubility data have been compared to the previously determined solubilities of two psychoactive cannabinoids i.e., (−)-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabinol (CBN), in supercritical CO2. An analytical method with a quasi-flow apparatus was used for the experimental determination. Within the investigated temperature and pressure range, the molar solubility of CBG ranged from 1.17 to 1.91×10−4 and the molar solubility of CBD ranged from 0.88 to 2.69×10−4. The solubility of the different cannabinoids in supercritical CO2 increases at 326K in the following order: Δ9-THC
The solubility of Δ9-tetrahydrocannabinol (Δ9-THC) in supercritical carbon dioxide has been determined at 315, 327, 334 and 345K and in the pressure range from 13.2 to 25.1MPa using an analytical method with a quasi-flow apparatus. Prior to performing these measurements, the method was validated by measuring anthracene solubilities and comparing these with literature values. The molar solubility for Δ9-THC ranged from 0.20 to 2.95×10−4. The data were correlated using the Peng–Robinson equation of state in combination with quadratic mixing rules. Deviations between calculated results and the experimental data ranged from 4.1 to 13.3% absolute average relative deviation (AARD).
This thesis concerns the production of natural compounds from plant material for pharmaceutical and food applications. It describes the production (extraction and isolation) of cannabinoids, the active components present in cannabis. Many cannabinoids have medicinal properties but not all cannabinoids are available in the (large) quantities necessary to develop new medicines, because so far, for large scale production, there are no economically and technically viable methods to extract those cannabinoids present in low quantities in the plant. Moreover, the currently used production process for the most important cannabinoid, tetrahydrocannabinol (Δ9-THC), has many drawbacks, such as the large use of the organic solvents, which is not only a burden to the environment but also to the safety of the operators, the production costs as well as the treatment of the produced waste. In this thesis, an alternative process using supercritical carbon dioxide is presented for the production of cannabinoids, including Δ9-THC, cannabinol (CBN), cannabigerol (CBG) and cannabidiol (CBD).
One of the steps of Δ9-THC production from cannabis plant material, is the decarboxylation reaction, transforming the Δ9-THC-acid naturally present in the plant into the psychoactive Δ9-THC. Experiments showed a pseudo first order reaction, with an activation barrier of 85 kJ.mol-1 and a pre-exponential factor of 3.7x108 s-1. Using molecular modeling, two options for an acid catalysed β-keto acid type mechanism were identified. Each of these mechanisms might play a role, depending on the actual process conditions. Formic acid was shown to be a good model for a catalyst of such a reaction. A direct keto-enol mechanism catalyzed by formic acid seems to be the best explanation for the observed activation barrier and the pre-exponential factor of the decarboxylation of Δ9-THC-acid. Evidence for this was found by performing an extraction experiment with Cannabis Flos. It revealed the presence of short chain carboxylic acids supporting this hypothesis.
Then, in order to develop the supercritical fluid extraction process, the solubility of Δ9-THC, CBN, CBG and CBD in supercritical carbon dioxide has been determined using an analytical method with a quasi-flow apparatus. First the solubility of Δ9-THC has been determined at 315, 327, 334 and 345 K and in the pressure range from 13.2 to 25.1 MPa. The molar solubility for Δ9-THC ranged from 0.20 to 2.95x10-4. Then, the solubility of CBN, CBG and CBD in supercritical carbon dioxide has been determined at 314, 327 and 334 K and in the pressure range from 11.3 to 20.6 MPa. The molar solubility of CBN, CBG and CBD ranged from 1.26 x 10-4 to 4.16 x 10-4, from 1.17 to 1.91 x 10-4 and from 0.88 to 2.69 x 10-4, respectively. These solubility data have been compared to each other. The solubility of the different cannabinoids in supercritical CO2 increases at 326 K in the following order: Δ9-THC < CBG < CBD < CBN. The solubility data were correlated using the Peng-Robinson equation of state in combination with Van der Waals mixing rules.
To continue, supercritical fluid extraction (SFE) using carbon dioxide was performed with Cannabis Sativa L. in a pilot scale set-up at 313 and 323 K in the pressure range from 18 to 23 MPa. The SFE yield of Δ9-THC is at maximum 98 %, which is comparable to classical hexane extraction. CBN and CBG can be extracted in higher amounts with SFE than with hexane extraction. Waxes are co-extracted with the cannabinoids. They can be easily removed via a winterization step. The purity of the final extract after winterization was 85 % Δ9-THC at the optimal experimental conditions found in these experiments. With a two-steps extraction, it is possible to selectively extract minor cannabinoids (i.e. CBN, CBD and CBG) in a first step at low pressure (~15 MPa), and Δ9-THC in a second step at higher pressure (~20 MPa).
The last step of the process is performed using Centrifugal Partition Chromatography. It uses a two-phase liquid system, instead of a solid stationary phase, as it is the case in High Pressure Liquid Chromatography (HPLC). Separation is realized by the partitioning of compounds between the two phases. With this technique, a successful separation of Δ9- THC, CBN and CBG is presented using the two-phase system hexane / acetone / acetonitrile. A purity higher than 99% is achieved with Δ9- THC. With CBN and CBG the best purity obtained is higher than 90%.
To conclude, an economical and ecological evaluation of two production routes to obtain pure Δ9-THC is presented: the current process using organic solvents is compared with the alternative process using supercritical carbon dioxide developed in this thesis. The alternative process is significantly cheaper than the current one, although the high price of the starting material cannabis dominates the ultimate cost price. From an ecological point of view, the alternative process is also more sustainable as it consumes less energy and generates less waste. Therefore, this alternative process is preferred from an economical and ecological point of view.
The optimisation of focused ultrasound extraction and supercritical fluid extraction of volatile oils and cannabinoids from marihuana has been accomplished by experimental design approach. On the one hand, the focused ultrasound extraction method of volatile compounds and cannabinoids was studied based on the optimisation of cyclohexane and isopropanol solvent mixtures, and the instrumental variables. The optimal working conditions were finally fixed at isopropanol/cyclohexane 1:1 mixture, cycles (3 s(-1) ), amplitude (80%) and sonication time (5 min). On the other hand, the supercritical fluid extraction method was optimised in order to obtain a deterpenation of the plant and a subsequent cannabinoid extraction. For this purpose, pressure, temperature, flow and co-solvent percentage were optimised and the optimal working conditions were set at 100 bar, 35°C, 1 mL/min, no co-solvent for the terpenes and 20% of ethanol for the cannabinoids. Based on the retention time locking GC-MS analysis of the supercritical fluid extracts the classification of the samples according to the type of plant, the growing area and season was attained. Finally, three monoterpenes and three cannabinoids were quantified in the ranges of 0.006-6.2 μg/g and 0.96-324 mg/g, respectively.
Two-step supercritical fluid extraction of rosemary leaves at selected conditions of pressure and temperature is proposed to divide the oleoresin into two fractions with different antioxidant activities and essential oil compositions. Rosemary leaves obtained from different sources have been extracted and evaluated in terms of antioxidant activity and essential oil yield and composition. Also, a new device is proposed to improve the performance of the technique in terms of sample collection after SFE. Keywords: Rosemary antioxidant; rosemary essential oil; supercritical fluid extraction; fractionation
Supercritical extraction and fractionation of natural matter is one of the early and most studied applications in the field of supercritical fluids. In the last 10 years, studies on the extraction of classical compounds like essential and seed oils from various sources: seeds, fruits, leaves, flowers, rhizomes, etc., with or without the addition of a co-solvent have been published. Supercritical extraction of antioxidants, pharmaceuticals, colouring matters, and pesticides has also been studied. The separation of liquid mixtures and the antisolvent extraction are other processes that can perform very interesting separations. Mathematical modelling has also been developed and refined for some of these processes.The objective of this review is to critically analyze traditional and new directions in the research on natural matter separation by supercritical fluids extraction and fractionation.
The use of smoked marijuana as a therapeutic agent is presently a matter of considerable debate in the United States. Many people suffering from a variety of disorders maintain that it is necessary for their adequate treatment. Yet, the evidence to support claims is insufficient for FDA approval. An interim solution is proposed which would allow patients referred by their physicians to participate in a 6-month program of legal marijuana availability, similar to the 'compassionate IND' program of a number of years ago. A technique similar to that used for post-marketing surveillance is proposed for obtaining quantitative data for a limited number of potential indications. These are: (1) nausea and vomiting associated with cancer chemotherapy or other causes, (2) weight loss associated with debilitating illnesses, (3) spasticity secondary to neurological diseases, and (4) chronic pain syndromes.
Research of the cannabinoid system has many similarities with that of the opioid system. In both instances, studies into drug-producing plants led to the discovery of an endogenous control system with a central role in neurobiology. Few compounds have had as much positive press from patients as those of the cannabinoid system. While these claims are investigated in disorders such as multiple sclerosis spasticity and pain, basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection. Large randomised clinical trials of the better known compounds are in progress. Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear.
The cannabis plant (Cannabis sativa L.) and products thereof (such as marijuana, hashish and hash oil) have a long history of use both as a medicinal agent and intoxicant. Over the last few years there have been an active debate regarding the medicinal aspects of cannabis. Currently cannabis products are classified as Schedule I drugs under the Drug Enforcement Administration (DEA) Controlled Substances act, which means that the drug is only available for human use as an investigational drug. In addition to the social aspects of the use of the drug and its abuse potential, the issue of approving it as a medicine is further complicated by the complexity of the chemical make up of the plant. This manuscript discusses the chemical constituents of the plant with particular emphasis on the cannabinoids as the class of compounds responsible for the drug's psychological properties.
In order to assess the current knowledge on the therapeutic potential of cannabinoids, a meta-analysis was performed through Medline and PubMed up to July 1, 2005. The key words used were cannabis, marijuana, marihuana, hashish, hashich, haschich, cannabinoids, tetrahydrocannabinol, THC, dronabinol, nabilone, levonantradol, randomised, randomized, double-blind, simple blind, placebo-controlled, and human. The research also included the reports and reviews published in English, French and Spanish. For the final selection, only properly controlled clinical trials were retained, thus open-label studies were excluded. Seventy-two controlled studies evaluating the therapeutic effects of cannabinoids were identified. For each clinical trial, the country where the project was held, the number of patients assessed, the type of study and comparisons done, the products and the dosages used, their efficacy and their adverse effects are described. Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer and AIDS), analgesics, and in the treatment of multiple sclerosis, spinal cord injuries, Tourette's syndrome, epilepsy and glaucoma.
Cannabis has been known for at least 4,000 years to have profound effects on the mind--effects that have provoked dramatically divergent attitudes towards it. Some societies have regarded cannabis as a sacred boon for mankind that offers respite from the tribulations of everyday life, whereas others have demonized it as inevitably leading to 'reefer madness'. The debate between the protagonists and prohibitionists has recently been re-ignited, but unfortunately this debate continues mainly in ignorance of our new understanding of the effects of cannabis on the brain and of studies that have quantified the extent of the risks of long-term use.
Makriyannis, Chapter 53 – Cannabis sativa and Hemp
- J A Hartsel
- J Eades
- B Hickory
J.A. Hartsel, J. Eades, B. Hickory, A. Makriyannis, Chapter 53 – Cannabis sativa
and Hemp, in: Nutraceuticals, 2016, pp. 735–754, http://dx.doi.org/10.1016/
B978-0-12-802147-7.00053-X.
Botanical Extraction System
- Sfe Waters
- Bio
Waters, SFE Bio-Botanical Extraction System, 2017 (http://www.waters.com/
waters/es AR/For-SFE-extraction-and-CO2-extraction/nav.
htm?cid=134826287&locale=es AR (Accessed 10 August 2015).
Cannabis inflorescence (Cannabis spp.): standards of identity, analysis, and quality control
Cannabis inflorescence (Cannabis spp.): standards of identity, analysis, and
quality control, Am. Herb. Pharm. (2013) 42-45.
Chapter 53 -Cannabis sativa and Hemp
- J A Hartsel
- J Eades
- B Hickory
- A Makriyannis
J.A. Hartsel, J. Eades, B. Hickory, A. Makriyannis, Chapter 53 -Cannabis sativa
and Hemp, in: Nutraceuticals, 2016, pp. 735-754, http://dx.doi.org/10.1016/
B978-0-12-802147-7.00053-X.
The therapeutic potential of cannabis
- D Baker
- G Pryce
- G Giovannoni
- A J Thompson
D. Baker, G. Pryce, G. Giovannoni, A.J. Thompson, The therapeutic potential of
cannabis, Lancet Neurol. 2 (2003) 291-298, http://dx.doi.org/10.1016/S1474-4422(03)00381-8.
Supercritical fluid extraction: recent advances and applications
- M Herrero
- J A Mendiola
- A Cifuentes
- E Ibáñez
M. Herrero, J.A. Mendiola, A. Cifuentes, E. Ibáñez, Supercritical fluid
extraction: recent advances and applications, J. Chromatogr. A 1217 (2010)
2495-2511, http://dx.doi.org/10.1016/j.chroma.2009.12.019.
Supercritical CO2 extraction of hemp (Cannabis sativa L.) seed oil
- K Aladić
- K Jarni
- T Barbir
- S Vidović
- J Vladić
- M Bilić
K. Aladić, K. Jarni, T. Barbir, S. Vidović, J. Vladić, M. Bilić, et al., Supercritical
CO2 extraction of hemp (Cannabis sativa L.) seed oil, Ind. Crops Prod. 76
(2015) 472-478, http://dx.doi.org/10.1016/j.indcrop.2015.07.016.
Ethanol and supercritical fluid extracts of hemp seed (Cannabis sativa L.) increase gene expression of antioxidant enzymes in HepG2 cells
- S Hong
- K Sowndhararajan
- T Joo
- C Lim
- H Cho
- S Kim
S. Hong, K. Sowndhararajan, T. Joo, C. Lim, H. Cho, S. Kim, et al., Ethanol and
supercritical fluid extracts of hemp seed (Cannabis sativa L.) increase gene
expression of antioxidant enzymes in HepG2 cells, Asian Pacific J. Reprod. 4
(2015) 147-152, http://dx.doi.org/10.1016/S2305-0500(15)30012-9.
Extraction and solubility evaluation of functional seed oil in supercritical carbon dioxide
- K Tomita
- S Machmudah
- A T Quitain
- M Sasaki
- R Fukuzato
- M Goto
K. Tomita, S. Machmudah, A.T. Quitain, M. Sasaki, R. Fukuzato, M. Goto,
Extraction and solubility evaluation of functional seed oil in supercritical
carbon dioxide, J. Supercrit. Fluids 79 (2013) 109-113, http://dx.doi.org/10.
1016/j.supflu.2013.02.011.
Solubility of non-psychoactive cannabinoids in supercritical carbon dioxide and comparison with psychoactive cannabinoids
- H Perrotin-Brunel
- M C Kroon
- M J E Van Roosmalen
- J Van Spronsen
- C J Peters
- G.-J Witkamp
H. Perrotin-Brunel, M.C. Kroon, M.J.E. van Roosmalen, J. van Spronsen, C.J.
Peters, G.-J. Witkamp, Solubility of non-psychoactive cannabinoids in
supercritical carbon dioxide and comparison with psychoactive cannabinoids,
J. Supercrit. Fluids 55 (2010) 603-608, http://dx.doi.org/10.1016/j.supflu.
2010.09.011.
Optimisation and characterisation of marihuana extracts obtained by supercritical fluid extraction and focused ultrasound extraction and retention time locking GC-MS
- J Omar
- M Olivares
- M Alzaga
- N Etxebarria
J. Omar, M. Olivares, M. Alzaga, N. Etxebarria, Optimisation and
characterisation of marihuana extracts obtained by supercritical fluid
extraction and focused ultrasound extraction and retention time locking
GC-MS, J. Sep. Sci. 36 (2013) 1397-1404, http://dx.doi.org/10.1002/jssc.
201201103.