Journal of Food Processing & Technology

Characterization of Traditional Chinese Medicine (TCM) Extract: Chemical Compositions, Solution Environment and its Implication in Membrane Process

Wenwei Zhong¹, Liwei Guo^2* and Haoran Zeng^{2 1}School of Chinese Medicinal Resource, Guangdong Pharmaceutical University, Yunfu 527322, Guangdong, China
²Guangzhou Bio-green Technology Co., Ltd., Guangzhou 511455, Guangdong, China
^*Correspondence: Liwei Guo, Guangzhou Bio-green Technology Co., Ltd., Guangzhou 511455, Guangdong, China, Email:

Received: 15-May-2023, Manuscript No. JFPT-23-21356; Editor assigned: 17-May-2023, Pre QC No. JFPT-23-21356 (PQ); Reviewed: 31-May-2023, QC No. JFPT-23-21356; Revised: 07-Jun-2023, Manuscript No. JFPT-23-21356 (R); Published: 14-Jun-2023, DOI: 10.35248/2157-7110.23.14.1022

Introduction

Modern analytical approaches have aided the identification of compounds in food system, as well as the measurement of physiochemical properties of the system. Processing of food can be optimized by monitoring the concentration of specific compounds, and physiochemical properties including the change in rheology and Total Soluble Solids (TSS) [1-4]. Though analytical chemical approaches have advanced to the extent that characterization of food system empowers process design and optimization, the characterization of TCM extracts has other aspects to address.

Most TCM extracts are generally viewed as complex systems where the combination of compositions act integratively as effective drug [5]. It is generally believed that TCM extract consists of various compounds, acting towards multiple targets in different combinations [6]. The most apparent challenge for TCM processing remains as the characterization of total compositions, which is essential to map the composition-target relationship for drug discovery and development.

Processing of the TCM extracts including extraction, purification, concentration and drying processes is a critical parameter on the effectiveness of the final products. Due to the multi-target properties of TCM extract, it is predominant to retain all active components in the TCM extracts during downstream processing where extreme processing parameters can result in the removal of active compounds further affecting the final drug efficacy adversely. Researchers have shed lights on the implementation of membrane technology in TCM manufacturing for its ability to process the extract at mild conditions. The concentration of Yi Mu Cao extract the dried roots from Leonurus japonicus Houtt was achieved by membrane distillation [7]. The concentration of Yu-Ping-Feng-San- Decoction [8], and Si-Jun-Zi-Decoction were achieved in reverse osmosis units [9]. Refinement of Qing-Luo-Tong-Bi-Decoction was achieved in an ultrafiltration unit [10].

Purification and concentration by membrane technologies are largely dependent on the compounds to be retained or transported, as well as the total solution environment. Microporous membranes act as a filter by size whereas the mass transfer is governed by the synergistic effects of size, special orientation, and affinity with membrane materials for both ultrafiltration and nanofiltration. It has been observed that compounds with smaller molecular weight than the cut-off weight of the membranes were rejected, resulting in reduced concentration of the active compounds in the final product of TCM [11].

The characterization on the total compositions of the TCM extracts has been a challenge as abovementioned for the evaluation of process design, where compositions of the TCM extracts pose significant impact on the physiochemical properties of the solution via microscopic interactions. The lack of characterization approaches of the solution microenvironment suggested the existence of a gap between the analytical methods available and the approaches can be applied to communicate TCM extracts with downstream processing (i.e. membrane technology).

This review aims on outlining the characterization approaches currently applied in TCM processing and methods to visualize the micro-environment of the herbal extracts solution. Novel attempts on bridging the gap between modern analytical chemistry and visualization of solution micro-environment were also discussed, to communicate the complex solution environment with membrane processes.

Literature Review

Membrane technology in food and pharmaceutical processing

Outside of its conventional application in wastewater treatment, membrane technology has been widely employed in many food processing scenarios. The implementation of membrane technologies mostly covers the concentration and flavor reservation in beverages and fruit juice processing. The fractionation of phytosterols and proteins in the fruit juice was realized via ultrafiltration membrane processing [12]. Forward osmosis processes have been implemented in many water removal processes [13,14], such as fruit juice [15], and tea extract concentration [16]. Extracts treated by membranes exhibited higher retention on key compounds such as thermo-sensitive compounds (i.e. catechins). The production of non-alcoholic wine is generally produced by the integrated membrane processes of nanofiltration for dealcoholization [17], and pervaporation for aroma recovery [18].

Pharmaceutical processing on the other hand, has a rather subtle requirement for both the retention and removal rate for specific compounds, hence resulting in limited research and applications of membrane technology in pharmaceutical processing. The most promising application of membrane technology for pharmaceutical purposes has been realized in the Traditional Chinese Medicine (TCM) sector for herbal extract processing.

TCM extract processing by membrane technology

Microfiltration membranes acting like a size sieving filter depending on the pore size and structures, are believed to have the ability to obtain target compounds with minimum loss, where it is generally accepted that the molecular weight of the target compounds are below a few thousand Da in TCM extracts [19]. Previous studies suggested that the characterization of TCM aqueous environment is of great interest for process design and product quality control by membrane process. The physiochemical properties of the aqueous environment poses significant impact on the membrane performance when processing herbal extracts such as TCM extracts [20]. Hence the characterization and quantification of herbal extracts solution environment is regarded as a pivotal aspect for the design of membrane process.

Conventional characterization approaches in membrane technology includes the characterization of membrane properties, and the characterization of both the feed and permeate. Rejections of the membrane process can be evaluated from the measurement of the conductivity meter as an indication of total dissolved solids (TDS) and total organic compounds (TOC) in the permeate collected, whereas chemical compositions can be characterized by liquid chromatography for specific compounds. The characterization and quantification have always been a challenge in complex herbal extract systems, correlating the process parameters, chemical compositions and drug efficacy. The conventional characterization approaches used in membrane technology is no longer sufficient for pharmaceutical processing of TCM extracts. It remains as a great challenge to quantify the TCM solution characteristics for membrane processing. There have been attempts to characterize and quantify the solution environment, enabling comprehensive research into the interaction between membranes and extract solution.

For instance, Brix is an effective approach to indicate total soluble solids in the aqueous system, measured by a refractometer. Li, et al. characterized the change in physiochemical properties of the aqueous extract environment by the measurement of the refractometer and evaluated the energy consumption of Yu-Ping-Feng-San extracts concentration process by membrane technologies [8]. The existence of certain compounds could also cause severe foaming in the system [9], resulting in reduced water removal efficiency and loss of active ingredients from overflowing.

Apart from the physiochemical properties of the solution environment, the micro-structure, microscopic state and chemical composition of the specific compounds are also critical to the separation efficiency by interacting with the membrane surface and pores [11,21]. We believe the visualization of solution environment of TCM extracts involves the characterization on the compositions, allowing further analysis of molecular interaction between compounds in the microenvironment.

Characterization of chemical compositions in the herbal extract

The characterization of chemical compositions has been a great challenge in food and pharmaceutical processes involving herbal extracts. The conventional characterization for composition analysis with known information and confirmed structures is generally achieved by chromatography (i.e. high performance liquid chromatography HPLC, and gas chromatography GC) and UV-Vis spectrometer. Specific compounds, also known as biomarkers are generally identified and quantified by HPLC and GC approaches, by recognizing the peaks of absorbance at certain retention time [22,23]. Group of compounds with similar functional groups (i.e. total flavonoids) were generally detected using UV-Vis spectrometer [24].

The composition of TCM herbal extracts after membrane processing was verified by measuring the concentration of target compounds by chromatography and UV-Vis spectrometer and evaluate the retention and rejection rate in most reported studies [10,25-29]. It has been used to verify the retention of certain substances in Chinese medicine extract by membrane processes.

Total compositions are generally characterized by fingerprints obtained via the means of chromatography and spectrum [30-32]. Particularly, the retentate of concentration process by nanofiltration and reverse osmosis is subjected to HPLC testing to access similarity of compositions before and after the membrane process to evaluate the integrity of the total compositions [9].

The quantification of non-target compounds in the extract system is still regarded as a challenge due to the lack of reference. Mass Spectroscopy (MS) is a common approach to determine the molecular weight for unknown compounds [33] while Nuclear Magnetic Resonance (NMR) spectroscopy is a popular mean to determine the structures of the unknown compounds. Recent studies suggested that key ion filtering and mass defect filtering by liquid chromatography and MS were used to identify non-target compounds [34-36].

The concept of ‘material basis-Q-markers’ was proposed to facilitate an efficient approach to reflect the effects of the compositions and manufacturing process on the TCM products. The approach involves the chemometrics characterization with the aid of modern algorithm from data science coupled with the conventional chromatography [37], where pattern recognition is implemented for correlating the drug properties with efficacy in a complex extract system. Particularly, chemical fingerprints and metabolic fingerprints (i.e. pharmacodynamics, and network pharmacology) were integrated to identify the Q-markers Alisma orientale (Sam). Juzep. [38]. The concept of material basis-Qmarkers will help the research and implementation of membrane technology for TCM processing to evaluate the effectiveness of the process.

Visualization of the solution environment

Advanced techniques are applied to aid the visualization of microscopic interactions in the complex solution environment. Fluorescence quenching was applied in the aqueous system of the tea extracts to estimate the binding ability between polyphenols and β-casein as proteins by measuring the fluorescence intensity [39]. Change in surface hydrophobicity of the specific molecules in the solution environment can also be estimated via the measurement of fluorescence intensity [40]. These approaches could be applied to aid the quantification of interaction between compounds in complex extract system and membrane surface, further elucidating the mass transfer mechanism in membrane processing.

Furthermore, the microscopic interactions could also pose substantial impact on its physiochemical properties. Investigation on foaming behavior in natural surfactants system of saponins has involved analytical methods [41-44], such as the measurement of surface tension, interfacial rheology, surface elasticity and the microscopic morphologies of the bubbles. This could provide innovative perspectives into correlating the physiochemical with chemical compositions in complex systems of herbal extracts, translating to parameters recognized in the mass transfer model in separation processes.

Novel approaches are introduced to visualize the effect of microenvironment on membrane performances. In line near-infrared spectroscopy as an emerging Process Analytical Technology (PAT), has been employed in food processing to replace off-line HPLC for indication of concentrations [45]. Near-infrared spectroscopy was implemented to indicate protein concentration with proper calibration [46]. With real-time knowledge in concentration change, it is possible to study the instant transport mechanism of membrane process in a complex system.

Membrane processes are also largely dependent on the physiochemical properties of the solution environment. Visualization on the rheological and microstructural properties in skim milk processing in an ultrafiltration unit was attempted, to evaluate the Bulk Nanobubbles (BNB) on fouling propensity [47]. Tan, et al. proposed that the foaming in Si-Jun-Zi Decoction can be characterized via the macroscopic observation of foam properties and the measurement of physiochemical properties (surface tension, zeta potential etc.) [9]. The quantification of foaming in TCM solution environment was correlated to the physiochemical properties and transport mechanism of RO process.

Discussion

The characterization of the TCM extracts has always been a challenge. Specific compounds in the extract solution can be easily quantified by analytical approaches, while the identification and quantification of the compounds hardly reflect the total solution environment. The compounds present in the solution interacts at microscopic scale (molecular adsorption, hydrophobic interaction etc.). TCM extract is a complex system consists of thousands of chemical compounds where the combinations of various compounds act integratively towards multiple targets, showing total drug efficacy. This could further influence the physiochemical properties of the total solution environment at macroscopic aspect and the retainment rate of the bioactive compounds, eventually the total drug efficacy is compromised.

Separation technologies implemented in TCM pharmaceutical processing are largely reliant on the compound properties (size, interactions etc.), as well as the physiochemical of the solution environment. For example, the concentration of TCM extracts requires constant removal of water and changing the physiochemical properties of the solution, posing significant effect on the water removal rate in membrane distillation [25]. The characterization of the change in physiochemical can help research in quantifying the effects of physiochemical properties in the TCM solution on the transport mechanism of membrane. Attempts have been demonstrated to characterize the solution environment to aid the visualization of total compounds in terms of microscopic interactions, physiochemical properties, and to quantify their effects on the mass transfer in separation technologies. With knowledge available on the rejection and retention of specific compounds or group compounds during membrane processes, design of the membrane and process can be achieved to acquire comprehensive active compounds in the TCM extracts showing total drug efficacy. Undesirable phenomena in the TCM extracts such as foaming can be mitigated and improvement of mass transfer can be anticipated in membrane processing [9].

Conclusion

Processing of herbal extracts for food purposes and TCM extracts share a great number of similarities while the major difference between these two lies on the characterization and evaluation of the final products. While the characterization of total composition still remains as a great challenge to identify the correlation of drug efficacy and the compound compositions for TCM extracts, fingerprints analysis of the extracts by modern analytical has facilitated the evaluation of the TCM products via various processing conditions, particularly including membrane separation technologies. The implementation of modern analytical techniques for solution environment characterization might be able to translate the properties of TCM extracts to the transport parameters of membrane processes.

References

1. Igual M, Martínez-Monzó J. Physicochemical properties and structure changes of food products during processing. Foods. 2022; 11(15): 2365.

   [CrossRef] [Google Scholar] [PubMed]

2. Abdullah N, Chin NL. Optimising tropical fruit juice quality using thermosonication-assisted extraction via blocked face-centered composite design. Processes. 2021;9(1):3.

   [Crossref] [Google Scholar]

3. Leneveu-Jenvrin C, Quentin B, Assemat S, Remize F. Maintaining physicochemical, microbiological, and sensory quality of pineapple juice (Ananas comosus, Var. ‘Queen Victoria’) through mild heat treatment. Processes. 2020;8:1186.

   [Crossref] [Google Scholar]

4. Putnik P, Lorenzo JM, Barba FJ, Roohinejad S, Jambrak AR, Granato D, et al. Novel food processing and extraction technologies of high-added value compounds from plant materials. Foods. 2018;7(7):106.

   [Crossref] [Google Scholar] [PubMed]

5. Marshall AC. Traditional Chinese medicine and clinical pharmacology. In: Hock FJ, Gralinski MR. (eds.) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Cham: Springer International Publishing. 2020.

6. Huo X, Gu Y, Zhang Y. The discovery of multi-target compounds with anti-inflammation activity from traditional Chinese medicine by TCM-target effects relationship spectrum. J Ethnopharmacol. 2022;293: 115289.

   [Crossref] [Google Scholar] [PubMed]

7. Ding Z, Liu L, Yu J, Ma R, Yang Z. Concentrating the extract of traditional Chinese medicine by direct contact membrane distillation. J Membr Sci. 2008;310(1-2):539-549.

   [Crossref] [Google Scholar]

8. Li W, Li Q, Guo L, Liu J, Wang K, Zhong W. Traditional Chinese Medicine extract properties incorporated energy analysis for membrane concentration processes. Membranes (Basel). 2021;11(9):673.

   [Crossref] [Google Scholar] [PubMed]

9. Tan S, Li Q, Guo L, Wang Y, Zhong W. Investigation of foaming behavior in herbal extracts via the characterization of solution environment for reverse osmosis concentration. Food Bioprod Process. 2023;137:28-44.

   [Crossref] [Google Scholar]

10. Liu H, Tang Z, Cui C, Sun C, Zhu H, Li B, et al. Fouling mechanisms of the extract of traditional Chinese medicine in ultrafiltration. Desalination. 2014;354:87-96.

    [Crossref] [Google Scholar]

11. Wang Q, Zhang Y, Zhang X, Li Q, Huang M, Huang S, et al. A study of the mechanism and separation of structurally similar phenolic acids by commercial polymeric ultrafiltration membranes. Membranes. 2022;12(3):285.

    [Crossref] [Google Scholar] [PubMed]

12. Puggioni G, Abd-Razak NH, Amura IF, Bird MR, Emanuelsson EAC, Shahid S. Preparation and benchmarking of highly hydrophilic polyaniline poly(2-acrylamido-2-methyl-1-propanesulfonic acid) PANI PAMPSA membranes in the separation of sterols and proteins from fruit juice. Food Bioprod Process. 2022;134:109-120.

    [Crossref] [Google Scholar]

13. Akhtar A, Singh M, Subbiah S, Mohanty K. Sugarcane juice concentration using a novel aquaporin hollow fiber forward osmosis membrane. Food Bioprod Process. 2021;126:195-206.

    [Crossref] [Google Scholar]

14. Julian H, Yaohanny F, Devina A, Purwadi R, Wenten IG. Apple juice concentration using Submerged Direct Contact Membrane Distillation (SDCMD). J Food Eng. 2020;272:109807.

    [Crossref] [Google Scholar]

15. Tavares HM, Tessaro IC, Cardozo NSM. Concentration of grape juice: Combined forward osmosis/evaporation versus conventional evaporation. IFSET. 2022;75:102905.

    [Crossref] [Google Scholar]

16. Bardhan A, Subbiah S, Mohanty K. Optimisation of multi-component inorganic salt composition as draw solute for preparation of concentrated tea extract using forward osmosis process. Food Bioprod Process. 2023;138:126-138.

    [Crossref] [Google Scholar]

17. Catarino M, Mendes A. Dealcoholizing wine by membrane separation processes. IFSET. 2011;12:330-337.

    [CrossRef] [Google Scholar]

18. Castro-Muñoz R. Pervaporation-based membrane processes for the production of non-alcoholic beverages. J Food Sci Technol. 2019;56(5): 2333-2344.

    [CrossRef] [Google Scholar] [PubMed]

19. Talukder ME, Alam F, Mishu MMR, Pervez MN, Song H, Russo F, et al. Sustainable membrane technologies for by-product separation of non-pharmaceutical common compounds. Water. 2022;14(24):4072.

    [Crossref] [Google Scholar]

20. Li B, Huang M, Fu T, Pan L, Yao W, Guo L. Microfiltration process by inorganic membranes for clarification of TongBi liquor. Molecules. 2012;17(2):1319-34.

    [Crossref] [Google Scholar] [PubMed]

21. Li C, Ma Y, Gu J, Zhi X, Li H, Peng G. A green separation mode of synephrine from Citrus aurantium L. (Rutaceae) by nanofiltration technology. Food Sci Nutr. 2019;7(12):4014-4020.

    [Crossref] [Google Scholar] [PubMed]

22. Abashev M, Stekolshchikova E, Stavrianidi A. Quantitative aspects of the hydrolysis of ginseng saponins: Application in HPLC-MS analysis of herbal products. J Ginseng Res. 2021;45(2):246-253.

    [Crossref] [Google Scholar] [PubMed]

23. Ueta I. Gas chromatographic determination of volatile compounds. Anal Sci. 2022;38(5):737-738.

    [Crossref] [Google Scholar] [PubMed]

24. Konieczynski P, Viapiana A, Lysiuk R, Wesolowski M. Chemical composition of selected commercial herbal remedies in relation to geographical origin and inter-species diversity. Biol Trace Elem Res. 2018;182(1):169-177.

    [Crossref] [Google Scholar] [PubMed]

25. Li C-Y, Ma Y, Ma L, Zhi X-L, Peng G-P. Improving the clarity and sensitization of polysorbate 80 by ultrasonic-assisted ultrafiltration technology. Eur J Pharm Sci. 2021;159:105719.

    [Crossref] [Google Scholar] [PubMed]

26. Li G, Li S. Resources recycle of Traditional Chinese Medicine (TCM) wastewater 2: The UF-FO-MD hybrid system and wetting prevention. Desalination. 2022;540:115968.

    [Crossref] [Google Scholar]

27. Wang X, Feng H, Muhetaer H, Peng Z, Qiu P, Li W, et al. Studies on the separation and purification of the caulis sinomenii extract solution using microfiltration and ultrafiltration. Separations. 2021;8(10):185.

    [Crossref] [Google Scholar]

28. Zhong W, Zhao Y, Chen S, Zhong J, Guo L, Zheng D, et al. Resources recycle of Traditional Chinese Medicine (TCM) wastewater 1: Effectiveness of the UF-MD hybrid system and MD process optimization. Desalination 2021;504:114953.

    [Crossref] [Google Scholar] (All versions)

29. Lu D, Liu H, Tang Z, Wang M, Song Z, Zhu H, et al. Anti-Pectin fouling performance of dopamine and (3-Aminopropy) Triethoxysilane-Coated PVDF ultrafiltration membrane. Membranes. 2022;12:740.

    [Crossref] [Google Scholar] [PubMed]

30. Bārzdiņa A, Paulausks A, Bandere D, Brangule A. The potential use of herbal fingerprints by means of HPLC and TLC for characterization and identification of herbal extracts and the distinction of Latvian native medicinal plants. Molecules. 2022;27(8): 2555.

    [Crossref] [Google Scholar] [PubMed]

31. Luthria DL, Mukhopadhyay S, Robbins RJ, Finley JW, Banuelos GS, Harnly JM. UV spectral fingerprinting and analysis of variance-principal component analysis: A useful tool for characterizing sources of variance in plant materials. J Agric Food Chem. 2008;56:5457-62.

    [Crossref] [Google Scholar] [PubMed]

32. Agatonovic-Kustrin S, Gegechkori V, Petrovich DS, Ilinichna KT, Morton DW. HPTLC and FTIR fingerprinting of olive leaves extracts and ATR-FTIR characterisation of major flavonoids and polyphenolics. Molecules. 2021;26(22):6892.

    [Crossref] [Google Scholar] (All versions) [PubMed]

33. Mclafferty FW, Stauffer DA, Loh SY, Wesdemiotis C. Unknown identification using reference mass spectra. Quality evaluation of databases. J Am Soc Mass Spectrom. 1999;10(12):1229-1240.

    [Crossref] [Google Scholar] [PubMed]

34. Shi X-J, Yang W-Z, Qiu S, Yao C-L, Shen Y, Pan H-Q, et al. An in-source multiple collision-neutral loss filtering based nontargeted metabolomics approach for the comprehensive analysis of malonyl-ginsenosides from Panax ginseng, P. quinquefolius, and P. notoginseng. Anal Chim Acta. 2017;952: 59-70.

    [Crossref] [Google Scholar] [PubMed]

35. Ma X-D, Fan Y-X, Jin C-C, Wang F, Xin G-Z, Li P, et al. Specific targeted quantification combined with non-targeted metabolite profiling for quality evaluation of Gastrodia elata tubers from different geographical origins and cultivars. J Chromatogr A. 2016;1450:53-63.

    [Crossref] [Google Scholar] [PubMed]

36. Zuo M-T, Liu Y-C, Sun Z-L, Lin L, Tang Q, Cheng P, et al. An integrated strategy toward comprehensive characterization and quantification of multiple components from herbal medicine: An application study in Gelsemium elegans. Chin Herb Med. 2021;13(1):17-32.

    [CrossRef] [Google Scholar] [PubMed]

37. He M, Zhou Y. How to identify “Material basis–Quality markers” more accurately in Chinese herbal medicines from modern chromatography-mass spectrometry data-sets: Opportunities and challenges of chemometric tools. Chin Herb Med. 2021;13(1):2-16.

    [Crossref] [Google Scholar] [PubMed]

38. Liao M, Shang H, Li Y, Li T, Wang M, Zheng Y, et al. An integrated approach to uncover quality marker underlying the effects of Alisma orientale on lipid metabolism, using chemical analysis and network pharmacology. Phytomedicine. 2018;45:93-104.

    [Crossref] [Google Scholar] [PubMed]

39. Wan J-Y, Long Y, Zhang Y-L, Xiang Y, Liu S-Y, Li N, et al. A novel technology to reduce astringency of tea polyphenols extract and its mechanism. Chin Herb Med. 2021;13(3):421-429.

    [Crossref] [Google Scholar] [PubMed]

40. Dai T, Mcclements DJ, Hu T, Chen J, He X, Liu C, et al. Improving foam performance using colloidal protein–polyphenol complexes: Lactoferrin and tannic acid. Food Chem. 2022;377:131950.

    [Crossref] [Google Scholar] [PubMed]

41. Labarre L, Vigolo D. Microfluidics approach to investigate foam hysteretic behaviour. Microfluid Nanofluidics. 2019;23:1-10.

    [Crossref] [Google Scholar]

42. Hudson P. Investigating foaming solutions generated by NaOH extraction of plant materials. Doctor of Philosophy, University of Birmingham. 2014.

    [Crossref] [Google Scholar]

43. Giacomin CE, Fischer P. Black tea interfacial rheology and calcium carbonate. Physics of Fluids. 2021;33:092105.

    [Crossref] [Google Scholar]

44. Tsibranska S, Tcholakova S, Golemanov K, Denkov N, Pelan E, Stoyanov SD. Role of interfacial elasticity for the rheological properties of saponin-stabilized emulsions. J Colloid Interface Sci. 2020;564:264-275.

    [Crossref] [Google Scholar] [PubMed]

45. Huang H, Yu H, Xu H, Ying Y. Near infrared spectroscopy for on/in-line monitoring of quality in foods and beverages: A review. J Food Eng. 2008;87:303-313.

    [Crossref] [Google Scholar]

46. Tonolini M, van den Berg FWJ, Skou PB, Sørensen KM, Engelsen SB. Near-infrared spectroscopy as a process analytical technology tool for monitoring performance of membrane filtration in a whey protein fractionation process. J Food Eng. 2023;350: 111487.

    [Crossref] [Google Scholar]

47. Babu KS, Amamcharla JK. Effect of bulk nanobubbles on ultrafiltration membrane performance: Physiochemical, rheological, and microstructural properties of the resulting skim milk concentrate dispersions. J Food Eng. 2023;337:111238.

    [Crossref] [Google Scholar]