Formation of Cyclodextrin Inclusion Complex
INQUIRY
There are several methods for the formation of cyclodextrin (CD) inclusion complexes, including the co-precipitation method, kneading method, spray drying method, freeze drying method, colloid grinding method, microwave irradiation method, and supercritical fluid method. Since CD's cavity is able to encapsulate different types and sizes of guest molecules, the types of CD inclusion complexes also vary. Therefore, it is necessary to choose the appropriate method to prepare CD inclusion complexes according to the properties of the guest molecules and the types of inclusion complexes [1],[2]. Here we mainly introduce three methods for the formation of CD inclusion compounds: co-precipitation, kneading, and spray drying.
Co-Precipitation
The co-precipitation method is suitable for water-insoluble guest molecules. It involves dissolving guest molecules in a solvent, adding CDs, and precipitating to obtain CD inclusion complex crystals. There are two options for solvents to dissolve guest molecules, namely saturated aqueous solutions and organic solvents.
Saturated aqueous solution
The process is to add guests to the saturated CDs aqueous solution, stir the mixture at an appropriate temperature for a period of time, and then cool, crystallize and dry to obtain clathrate crystals. The method is simple and efficient, making it one of the most commonly used CD formation methods. However, a large amount of wastewater will be generated during this preparation process, and due to the complex subsequent wastewater treatment process, this method is only suitable for laboratory use [3].
Organic solvent
In this process, guests are dissolved in organic solvents such as chloroform, benzene, and ether, and an appropriate amount of CD is added under stirring. A precipitate forms when the solution is cooled after a period of time. It is washed with an organic solvent and dried to obtain CD inclusion complex crystals. This method has been used for the encapsulation of drugs such as oxaprozine and trans-anethole [4,5].
Kneading
The kneading method, also called the paste method, is a simple method for forming CD inclusion complexes. This method is suitable for dissolving guests with poor water solubility. For guest molecules whose dissolution occurs slowly during complex formation, it provides high efficiency. The process is as follows: (a) Add the liquid or dissolved solid guests to a slurry of CD, and obtain the paste by kneading in a mortar. (b) Dry the paste and wash the mixture solid to remove free particles adsorbed on the CD surface. (c) Dry the solid under vacuum to obtain the final CD inclusion complex. The kneading method has potential for large-scale production [1,3].
Spray Drying
Another method of forming CD inclusion complexes is spray drying, which is one of the earliest methods. This method has the advantages of simple operation and a fast drying speed. The preparation process is as follows: (a) Dissolve CD and guest molecules in deionized water to prepare a sample. (b) Set various parameters of the spray-dryer, including feeding speed, rotation speed, inlet temperature, and outlet temperature, and atomize the prepared mixed liquid sample under a certain pressure. (c) Mix the atomized fine particles with the heated air stream for drying. (d) Separate the dried target product particles from the gas stream and collect them. Spray drying is only applicable to thermally stable molecules and consumes a lot of energy, which limits its wide application [1].
References
- Zhou, J.; et al. Cyclodextrin inclusion complexes and their application in food safety analysis: recent developments and future prospects. Foods. 2022, 11 (23): 3871.
- Pilar, H.-S.; et al. Optimization of a method for preparing solid complexes of essential clove oil with beta-cyclodextrins. J. Sci. Food Agric. 2017, 97: 420–426.
- Cheirsilp, B.; Rakmai, J. Inclusion complex formation of cyclodextrin with its guest and their applications. Biol Eng Med. 2016, 2.
- Mennini, N.; et al. Analysis of physicochemical properties of ternary systems ofoxaprozin with randomly methylated-ß-cyclodextrin and l-arginine aimed to improve the drug solubility. J Pharma Biomed Anal. 2016, 129: 350–358.
- Cao, H.; et al. Enhancement of methanol resistance of Yarrowia lipolytica lipase 2 using ß- cyclodextrin as an additive: Insights from experiments and molecular dynamics simulation. Enzyme Microb Technol. 2015, 96: 157–162.
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