1.Preparation method of β-CD
1. 1.1 Saturated aqueous solution method: according to the different adding states of drugs, it can be divided into liquid-liquid method and liquid-solid method. The drug or other solution is added to the saturated β-CD aqueous solution, stirred at a specified temperature for a certain time, then cooled to crystallize, filtered and dried. This is the most commonly used method in the current research, which is generally carried out in magnetic stirrer or electric stirrer.
1.1.2 Ultrasonic method: Add the drug into β-CD saturated aqueous solution with ultrasonic crushing instrument or ultrasonic cleaning machine, select the appropriate ultrasonic intensity and time, and dispose the precipitated precipitate as described above. This method is simple and quick. The volatile oil inclusion complex prepared by ultrasonic method is easy to operate and has high inclusion rate. Compared with the saturated aqueous solution method prepared by the same process, the yield is 17.88% and the inclusion rate is 11.51% higher. The garlic oil inclusion compound obtained by this method can improve the yield and reduce the odor, which is considered superior to the electric stirring method.
1.1.3 Grinding method: The finished product can be obtained by mixing β-CD with quantitative solid drugs and grinding it in a ball mill or emulsion for a certain time. In the experiment, heme β-CD inclusion complex was prepared by grinding method, which increased the solubility and dissolution, improved the bioavailability of heme, concealed the fishy smell of heme, and opened up a good prospect for its processing into various dosage forms [4]. However, this method is only carried out in a small amount, and manual operation is not suitable for large-scale production. The colloid mill method instead of grinding method is fast, simple and suitable for industrial production.
1.1.4 Freeze drying is rarely used
1.1.5 Spray drying is rarely used
The properties of cyclodextrins
2.1 Inclusion complexes with unique inclusion properties can be formed with hydrophobic pharmaceutical small molecules soluble in water
Cyclodextrin has a hydrophobic internal cavity and a hydrophilic surface due to its structural characteristics. Therefore, it has unique inclusion properties and can form inclusion complexes with a variety of objects through weak interaction so as to change the physical and chemical properties of the object molecules. At the same time, because of the low toxicity and water solubility of cyclodextrin, the inclusion complex formed by cyclodextrin and hydrophobic small pharmaceutical molecules can be dissolved in water, thus improving the solubility of drugs, increasing the stability of drugs and improving the bioavailability and efficacy of drugs. And it allows a lot of chemical reactions to take place in water making the whole thing environmentally friendly.
2.2 Poor thermal stability, alkali stability and acid stability
Cyclodextrin is heat stable and has no fixed melting point. It begins to decompose when heated to about 200℃ and can be stored for a long time at room temperature. Stable to alkali, can form salt at high pH; It is less stable to acid, hydrolysis can occur in strong acid, and the rate of hydrolysis is obviously slower than that of starch. However, CD is stable in dilute acid at room temperature. CD is not hydrolyzed by β-amylase, but can be slowly hydrolyzed by β-amylase. In general, the larger the ring of CD, the faster the hydrolysis rate.
2.3 Difficult absorption in human body and less toxic
Cyclodextrin due to the larger molecules, in the human body is more difficult to absorb, most of the original form of excretion; The main site of absorption is the small intestine. The metabolism of cyclodextrin is mainly completed by the colonic flora, and the end products are CO2 and H2O. α-CD is the slowest and γ-CD is the fastest. Cyclodextrin has slight toxicity to biology and almost no toxicity after oral administration. In parenteral use,CD can interact with cell membrane components, resulting in cell damage. Long-term accumulation of cyclodextrin in human body will increase the burden of kidney.
2.4 Cheap and easy to get
The production process of cyclodextrin is simple, its physical and chemical properties are stable, and the production process is simple and easy to obtain.
