Cyclodextrin (abbreviated as CD) is a type of macrocyclic molecules linked by glucopyranose units through α-1,4-glycosidic bonds. Among them, the most common cyclodextrins contain 6, 7 and 8 glucose units, which are called α, β and γ-cyclodextrins respectively. The space structure of cyclodextrin is similar to a truncated cone, and the hydroxyl group of the glucose monomer is exposed on the outside. This special molecular structure makes the cyclodextrin have the special properties of hydrophilic outer edge and the hydrophobic inner cavity. Fat-soluble drug molecules can bind to the hydrophobic cavity of cyclodextrin to form host-guest inclusion compounds, thereby improving drug solubility, enhancing drug stability, reducing toxic and side effects, improving drug bioavailability, and masking the body smell of drugs, etc. Therefore, it is widely used in the pharmaceutical industry.
However, natural CD has certain limitations in some aspects, such as low water solubility, high toxicity and unfavorable use, etc. Through alkylation, hydroxy alkylation or esterification of free hydroxyl groups in the structure by means of chemical modification and other means, it can synthesize CD derivatives with good water solubility, amorphous, high physical stability and low physiological toxicity to improve its application performance and application range. Hydroxypropyl CD, methyl CD and sulfobutyl CD are commonly used currently.
1. Role of cyclodextrins in drug delivery system
Drug solubilization: solubility is one of the important parameters of the drug itself. CD polymer materials can form inclusion compounds with some poorly soluble drugs to greatly increase their solubility. CD materials that improve drug solubility are mostly modified CD molecules with good water solubility.
Improvement of drug stability: the drug CD inclusion compounds can be considered as a "protective coat" of polymer materials built around the drug molecules, which prevents unstable drug molecules from being affected by the surrounding sensitive environment, and protects the drug from hydrolysis, oxidation, enzymatic hydrolysis, isomeric rearrangement, etc. The improvement of drug stability depends on the impact of drug groups embedded in the inner cavity of CD on the overall drug molecular stability, and it is closely related to the stability of the drug CD inclusion compound.
Reducing the toxicity and side effects: the drug-CD inclusion compound can reduce the dosage of the drug to a certain extent, thereby reducing the toxicity and side effects of the drug. The CD can inhibit drug crystallization and reduce tissue toxicity caused by drug crystallization in some cases. The CD can also reduce the damage of drugs to blood vessels by blocking the direct contact of drug molecules with epithelial cells of the blood vessel wall.
Improvement of drug bioavailability and taste masking: CD improves the bioavailability of drugs mainly based on the improvement of the solubility and dissolution of insoluble drugs, so as to promote the effective absorption of gastrointestinal tract. In addition, by forming inclusion compounds with drugs, CD can also mask the odor of drugs and inhibit the volatilization of drugs.
2. Application of cyclodextrin in listed pharmaceutical products
2.1 Natural cyclodextrins
Natural α-CD and β-CD are the earliest CD materials used in pharmaceutical preparations and medical health supplies. The main functions of the CD in the listed preparations include solubilization, stabilization, promotion of dissolution, and masking the taste of the materials. For example, cefotiam hydrochloride tablets form a gel-like structure when exposed to water, which reduces the dissolution of the drug. After forming an inclusion compound with α-CD, α-CD can effectively inhibit the formation of gel and accelerate the dissolution of the drugs. Prostaglandin PGE2 is an oxytocin-like compound that can be used to help childbirth. However, PGE2 has poor chemical stability. Under certain circumstances, it is prone to hydrolyze, dehydrate or isomerize and lose its physiological activity. This shortcoming makes the administration route and application of prostaglandin PGE2 extremel...
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