Abstract:The solubility of artemisinin in pure methanol, ethyl acetate, acetone, acetonitrile, cyclohexane, toluene, and chloroform was measured by a synthetic method over the temperature range from (283.15 to 323.15) K at atmospheric pressure. The results show that the solubility of artemisinin increases with increasing temperature in all seven solvents. The experimental data were correlated using the modified Apelblat model, and the agreement with the experimental data was very good.
“…Stream concentration (in order to reduce its solvent content) is required for efficient crystallisation: antisolvent addition without API concentration results in low feed API mass fractions, with which crystallisation cannot be efficiently performed (concentration is below the solubility that would be reached at the bottom of the temperature range). In order to achieve the desired feed API concentrations, antisolvent must first be added, as toluene evaporation alone will exceed API saturation (Liu et al, 2009). The required antisolvent quantities to be added in each case have been calculated by performing isothermal flash calculations via the UniSim ® software suite (Honeywell, 2014).…”
Recent advances in pharmaceutical manufacturing technologies are showing the promise of continuous production: pharmaceutical firms currently rely on mature batch technology but increasingly evaluate the potential of Continuous Pharmaceutical Manufacturing (CPM). Continuous production methods have efficiency, cost, reliability and quality advantages: in this paper we evaluate and quantify these for the case of CPM of artemisinin, a key antimalarial Active Pharmaceutical Ingredient (API). Published reaction and unit operation data are analysed, static models are developed, and continuous plug flow reactors are designed for a reference case producing 100 kg of API per year. The small reactor volumes computed (19.72 mL and 78.72 mL) illustrate the capital expenditure and small footprint benefits of continuous manufacturing. Alternative CPM cases are also developed, whereby different continuous API recovery operations are evaluated in comparison to the base case; the latter employs a reported batch product recovery. Employing published solubility data as well as data estimated using the UNIFAC method, our systematic evaluation identifies ethanol (EtOH) and ethyl acetate (EtOAc) as promising candidate antisolvents for continuous crystallisation. For the same 100 kg per year production level of API, designs using continuous separation techniques can achieve significantly improved E-factor values (22.52 average) compared to the batch process (65.28), implying enhanced sustainability through reduced waste generation. This API of critical societal importance is a very promising candidate for CPM, with the future benefits of performing full analysis and technoeconomic optimisation evident.
“…Stream concentration (in order to reduce its solvent content) is required for efficient crystallisation: antisolvent addition without API concentration results in low feed API mass fractions, with which crystallisation cannot be efficiently performed (concentration is below the solubility that would be reached at the bottom of the temperature range). In order to achieve the desired feed API concentrations, antisolvent must first be added, as toluene evaporation alone will exceed API saturation (Liu et al, 2009). The required antisolvent quantities to be added in each case have been calculated by performing isothermal flash calculations via the UniSim ® software suite (Honeywell, 2014).…”
Recent advances in pharmaceutical manufacturing technologies are showing the promise of continuous production: pharmaceutical firms currently rely on mature batch technology but increasingly evaluate the potential of Continuous Pharmaceutical Manufacturing (CPM). Continuous production methods have efficiency, cost, reliability and quality advantages: in this paper we evaluate and quantify these for the case of CPM of artemisinin, a key antimalarial Active Pharmaceutical Ingredient (API). Published reaction and unit operation data are analysed, static models are developed, and continuous plug flow reactors are designed for a reference case producing 100 kg of API per year. The small reactor volumes computed (19.72 mL and 78.72 mL) illustrate the capital expenditure and small footprint benefits of continuous manufacturing. Alternative CPM cases are also developed, whereby different continuous API recovery operations are evaluated in comparison to the base case; the latter employs a reported batch product recovery. Employing published solubility data as well as data estimated using the UNIFAC method, our systematic evaluation identifies ethanol (EtOH) and ethyl acetate (EtOAc) as promising candidate antisolvents for continuous crystallisation. For the same 100 kg per year production level of API, designs using continuous separation techniques can achieve significantly improved E-factor values (22.52 average) compared to the batch process (65.28), implying enhanced sustainability through reduced waste generation. This API of critical societal importance is a very promising candidate for CPM, with the future benefits of performing full analysis and technoeconomic optimisation evident.
“…Moreover, a series of peaks of moderate intensity between wave numbers 1400 and 1700 cm -1 can be attributed to the elongation of the functional groups C = O and C = C due to the presence of ketones, esters, aldehydes and carboxylic acids. At 1038 cm -1 NE presents a peak which corresponds to alcoholic C-O vibration stretching (Moreno et al 2000; Moreno 2004; Pradhan & Sandle 1999; Terzyk et al 2003; Terzyk 2002; Liu et al 2009; Liu et al 2010). Figure 2
FTIR spectra for activated carbons.…”
Section: Resultsmentioning
confidence: 99%
“…The magnitude of the ΔH values lies in the range of 2.1 to 20.9 and 80 to 200 kJ/mol for physical and chemical adsorption, respectively. Generally, the ΔG is in the range of 0 to −20 kJ/mol and −80 to −400 kJ/mol for physical and chemical adsorption (Liu et al 2009 ; Liu et al 2010 ; Li et al 2005 ). A characteristic curve of acetaminophen for SGF obtained from the DR equation, Figure 9 , shows that the values of energy in the environment previously predicted.…”
Samples of commercial activated carbons (AC) obtained from different sources: Norit E Supra USP, Norit B Test EUR, and ML (Baracoa, Cuba) were investigated. The adsorption of acetaminophen, Co = 2500 mg/L, occured in simulated gastric fluid (SGF) at pH 1.2 in contact with activated carbon for 4 h at 310 K in water bath with stirring. Residual acetaminophen was monitored by UV visible. The results were converted to scale adsorption isotherms using alternative models: Langmuir TI and TII, Freundlich, Dubinin-Radushkevich (DR) and Temkin. Linearized forms of the characteristic parameters were obtained in each case. The models that best fit the experimental data were Langmuir TI and Temkin with R2 ≥0.98. The regression best fits followed the sequence: Langmuir TI = Temkin > DR > LangmuirTII > Freundlich. The microporosity determined by adsorption of CO2 at 273 K with a single term DR regression presented R2 > 0.98. The adsorption of acetaminophen may occur in specific sites and also in the basal region. It was determined that the adsorption process of acetaminophen on AC in SGF is spontaneous (ΔG <0) and exothermic (−ΔHads.). Moreover, the area occupied by the acetaminophen molecule was calculated with a relative error from 7.8 to 50%.
“…This solubility is measurable via different methods like the isothermal excess method or the polythermal method, e.g., [25]. Several solvents have been screened for artemisinin [26][27][28][29] and there are already described crystallization steps using ethanol, which are used commercially as re-crystallization steps [20]. Due to this, ethanol-mixtures are investigated focusing on target yield and process range.…”
Section: Raw and Purified Materialsmentioning
confidence: 99%
“…Due to this, ethanol-mixtures are investigated focusing on target yield and process range. In addition, acetone-water mixtures are also screened based on the good solving properties of the pure solvent for artemisinin [27,28], its high availability, and its usage as the extraction solvent in this process Part 1. This solubility of the target component can be influenced by different approaches like cooling, heating or evaporation.…”
In this study, process integration for crystallization of a priori purified Artemisia annua L. is investigated. For this total process, the integration operation boundaries and behavior of the crystals are studied. This is performed focusing on a conceptual process design study for artemisinin, aiming towards the development of a crystallization step under given parameters by process integration. At first, different crystallization systems consisting of ethanol-water or acetone-water mixtures are compared. In subsequent steps, the metastable zone width and the behavior of the crystals regarding agglomeration and breakage are checked. Furthermore, the sensitivities of process variables based on several process parameters are investigated. Additionally, the final process integration of crystallization as a combined purification and isolation step is studied.
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