Optimization of the Ethanol Recycling Reflux Extraction Process for Saponins Using a Design Space Approach

Abstract

A solvent recycling reflux extraction process for Panax notoginseng was optimized using a design space approach to improve the batch-to-batch consistency of the extract. Saponin yields, total saponin purity, and pigment yield were defined as the process critical quality attributes (CQAs). Ethanol content, extraction time, and the ratio of the recycling ethanol flow rate and initial solvent volume in the extraction tank (RES) were identified as the critical process parameters (CPPs) via quantitative risk assessment. Box-Behnken design experiments were performed. Quadratic models between CPPs and process CQAs were developed, with determination coefficients higher than 0.88. As the ethanol concentration decreases, saponin yields first increase and then decrease. A longer extraction time leads to higher yields of the ginsenosides Rb1 and Rd. The total saponin purity increases as the ethanol concentration increases. The pigment yield increases as the ethanol concentration decreases or extraction time increases. The design space was calculated using a Monte-Carlo simulation method with an acceptable probability of 0.90. Normal operation ranges to attain process CQA criteria with a probability of more than 0.914 are recommended as follows: ethanol content of 79–82%, extraction time of 6.1–7.1 h, and RES of 0.039–0.040 min−1. Most of the results of the verification experiments agreed well with the predictions. The verification experiment results showed that the selection of proper operating ethanol content, extraction time, and RES within the design space can ensure that the CQA criteria are met.

Rapid quantification of multi-components in alcohol precipitation liquid of Codonopsis Radix using near infrared spectroscopy (NIRS)

“…Flow rate was set at 1.0 ml/min, while the injection volume was 10 μl, and the detection wavelength was set at 269 nm. Sodium nitrite-aluminium nitrate (Shi et al, 2012) and tartrazine colorimetric methods (Gong et al, 2014a) were used to quantify total flavonoids and pigments, respectively. A gravimetric based loss-on-drying method was run to determine the concentration of total solid by hot air dying at 105 °C for 3 h.…”

“…Therefore, in this study, lobetyolin, total flavonoids, pigments, and total solid contents were taken into consideration and defined as critical quality attributes (CQAs) of the alcohol precipitation liquid. With the aim of accurately measuring these quality indices, high-performance liquid chromatography (HPLC) (Qiao et al, 2007;He et al, 2014;Kim et al, 2014), colorimetric assay (Han et al, 2013;Gong et al, 2014a), and gravimetric assay (Li et al, 2013) are most commonly adopted as standard quantitative methods. However, these methods are tedious and somewhat time-consuming, failing to satisfy the demand for real-time monitoring.…”

Optimization of a chromatographic process for the purification of saponins in Panax notoginseng extract using a design space approach

“…Analysis of variance was carried out and the statistical analysis was based on a confidence level of 0.90. The design space was calculated using a Monte-Carlo method with a program of Matlab (R2010b, Version 7.11, MathWorks, USA) [16]. Considering the sampling error, the response variables were assumed to follow a normal distribution.…”

“…The performance of a chromatographic process is influenced by many factors, such as the composition of load solution, flow rate and the composition of elution solvent [12][13][14][15]. In addition, in the chromatographic process for traditional Chinese medicine purification, the compositions of load solution are complicated [10,11,16,17]. Therefore maintaining batch-to-batch consistency is a challenging task in the chromatographic process for traditional Chinese medicine purification.…”

Minimising variation in aspalathin content of aqueous green rooibos extract: optimising extraction and identifying critical material attributes

“…Some flexibility can be built into the extract production process to ensure that variability in raw material quality can be accommodated, although without moving the product out of specification. The concept and application of the principles of QbD have not only been advocated for pharmaceutical product development, but also recently for the production of botanical drug products . Design of Experiments (DoE) employing experimental designs such as a central composite design (CCD) or a Box–Behnken design and multivariate statistics for the optimisation and establishment of a control space comprise the inherent elements of QbD …”