Process synthesis and optimization for the isolation and purification of paclitaxel from Taxus chinensis

Non-chromatographic Method for the Purification of High-Purity Paclitaxel from Taxus chinensis Using Tandem Cavitation Fractional Precipitation

“…Paclitaxel produced by plant cell culture is mostly accumulated in plant cells as an intracellular product. To use paclitaxel as an active pharmaceutical ingredient (API), high purity (>98%) separation and purification are essential [13]. However, the separation and purification processes for intracellular products account for more than 50% of the total manufacturing cost, so downstream processes must be designed well [14,15].…”

“…In earlier attempts, paclitaxel was extracted using chromatography as a pretreatment for purification or immediately purified crude paclitaxel (purity: ~0.5%) was extracted without pretreatment using high performance liquid chromatography (HPLC), which made it difficult to commercially mass-produce paclitaxel due to the high a quantity of organic solvent used and the short column lifetime [14,16]. Subsequently, a variety of pretreatment methods such as liquid-liquid extraction [13,17], adsorption [13,18], low-pressure liquid chromatography (LPLC) [19,20], and precipitation [13,21] were introduced to the process in order to enhance the final purification efficiency using chromatography [14]. To obtain high purity (>98%) products, multi-step chromatography (octadecylsilylate (ODS C18)-HPLC, silica-HPLC) or an integrated purification process of chromatography and crystallization is still needed [14,19,22,23].…”

“…Fractional precipitation is a highly effective and simple purification method based on solubility differences [13,29]. To shorten the long precipitation time (~3 days) of conventional fractional precipitation, studies have attempted to improve the precipitation efficiency using surface area increasing materials, but the precipitation still takes a long time, which limits its application for mass production [30,31].…”

Increased paclitaxel recovery from Taxus baccata vascular stem cells using novel in situ product recovery approaches

“…A technique that has proven to be especially effective in the recovery of paclitaxel using Taxus cell suspension cultures cells is the application of the macro-porous resin, XAD-4, where the use of the resin at day 7 of cultivation increased paclitaxel production by up to 70%, reaching concentrations of 2.7 mg/L (Kwon et al 1998 ). Other studies using solid adsorbents discovered that the use of sylopute (SiO 2 ) as adsorbent material in the extraction step enhanced the paclitaxel yield by 30 to 45% compared to methods with no adsorbent treatment (Min and Kim 2022 ). In the context of microbial cells, cultures of Aspergillus fumigatus and Alternaria tenuissima have been immobilised using different entrapment carriers (gelatin, agar and Arabic gum), increasing paclitaxel yields by 1.3- and 1.8-fold, respectively, compared to free cultures (El-Sayed et al 2019 ).…”

Non-chromatographic method for the purification of high purity paclitaxel from Taxus chinensis using tandem cavitation fractional precipitation

“…To shorten the long precipitation time (~3 days) of conventional fractional precipitation, studies have attempted to improve the precipitation efficiency using surface area increasing materials, but the precipitation still takes a long time, which limits its application for mass production [30,31]. Recently, cavitation-assisted fractional precipitation, which can dramatically decrease the precipitation time by using negative pressure and ultrasound-induced cavitation, has been developed [13,28,32]. In the case of ultrasonic cavitation fractional precipitation (precipitation solution: methanol/water ratio = 61.5:38.5, v/v), high purity (~74%) paclitaxel can be obtained in a short working time (<10 min) [32].…”