Beta-Cyclodextrin

Usage

Beta-cyclodextrin (βCD) is a cyclic oligosaccharide used as an excipient in pharmaceutical formulations. It is not classified as a drug itself, but rather as a pharmaceutical additive that modifies the properties of active pharmaceutical ingredients. It’s frequently employed to enhance the solubility, stability, and bioavailability of poorly water-soluble drugs. It is also used to reduce or prevent gastrointestinal and ocular irritation, reduce or eliminate unpleasant smells or tastes, and prevent pre-systemic drug-drug or drug-additive interactions.

Alternate Names

• βCD
• betadex
• Cyclomaltoheptaose
• Betadex NF

There are also chemically modified beta-cyclodextrins like hydroxypropyl-beta-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) which offer additional benefits, and are also considered as excipients.

How It Works

Pharmacodynamics: Beta-cyclodextrin itself does not exert a direct pharmacological effect on the body. Its primary function is to encapsulate drug molecules within its hydrophobic cavity, forming inclusion complexes. This complexation can alter the physicochemical properties of the drug, affecting its interaction with the body.

Pharmacokinetics: Beta-cyclodextrin is minimally absorbed after oral administration. A small amount of βCD is metabolized by the colonic microflora, and most is excreted unchanged in feces. At high doses cyclodextrins can cause reversible diarrhea and cecal enlargement in animals.

Mode of Action: Beta-cyclodextrin forms inclusion complexes with drug molecules through non-covalent interactions. The drug molecule enters the hydrophobic cavity of the cyclodextrin, while the outer surface of the cyclodextrin remains hydrophilic, improving the drug’s solubility in aqueous solutions.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Beta-cyclodextrin itself does not typically bind to receptors, inhibit enzymes, or modulate neurotransmitters. However, by altering the pharmacokinetics of drugs, it can indirectly influence these processes.

Elimination Pathways: βCD is primarily eliminated through fecal excretion. A small amount is metabolized by microflora in the colon.

Dosage

Beta-cyclodextrin is not a drug with its own inherent dosage. Its use is determined by the formulation of the specific drug product containing it. Safety studies suggest harmful effects are not expected below 20 mg/kg/day. Higher parenteral doses (>200 mg/kg/day for over 2 weeks) warrant caution, especially in patients with kidney disease. Pediatric data below 2 years of age is limited.

Side Effects

Beta-cyclodextrin is generally considered safe. At high doses, some individuals may experience diarrhea.

Contraindications

No absolute contraindications to beta-cyclodextrin as an excipient exist. However, caution is advised in patients with renal impairment, especially with high parenteral doses, due to potential accumulation.

Drug Interactions

Beta-cyclodextrin can enhance the absorption of some drugs, potentially leading to increased effects or side effects. Conversely, it may reduce the absorption of others. Drug-specific information should be consulted.

Pregnancy and Breastfeeding

Limited information is available regarding the use of beta-cyclodextrin during pregnancy and breastfeeding. Animal studies indicate no adverse developmental or reproductive effects at high doses. However, a case-by-case risk/benefit assessment should be conducted.

Drug Profile Summary

Mechanism of Action: Forms inclusion complexes with drugs, enhancing solubility, stability, and bioavailability.

Side Effects: Generally safe, diarrhea possible at high doses.

Contraindications: Caution with renal impairment, especially at high parenteral doses.

Drug Interactions: Can alter the absorption of co-administered drugs.

Popular Combinations

Beta-cyclodextrin is used in combination with various drugs, including piroxicam, doxycycline, and others, to improve their pharmaceutical properties.

Precautions

Assess renal function in patients receiving high parenteral doses. Limited safety data exists for children under 2 years of age.

FAQs (Frequently Asked Questions)

Q1: What is the role of beta-cyclodextrin in drug formulations? A: It acts as an excipient to enhance solubility, stability, and bioavailability of drugs, particularly those that are poorly soluble in water.

Q2: How does beta-cyclodextrin work? A: It forms inclusion complexes by trapping drug molecules within its hydrophobic cavity, leading to improved drug delivery.

Q3: Is beta-cyclodextrin safe? A: Generally considered safe, with diarrhea as a potential side effect at high doses.

Q4: Are there any contraindications to beta-cyclodextrin use? A: Use cautiously in patients with renal impairment, especially those receiving high parenteral doses. Pediatric data is limited.

Q5: Can beta-cyclodextrin interact with other drugs? A: It may alter drug absorption; consult drug-specific information.

Q6: Can beta-cyclodextrin be used during pregnancy or breastfeeding? A: Limited data; risk/benefit assessment should be done. Animal studies show no adverse effects at high doses.

Q7: How is beta-cyclodextrin eliminated from the body? A: Primarily via fecal excretion and a small amount metabolized by colonic microflora.

Q8: What are some examples of drugs commonly formulated with beta-cyclodextrin? A: Examples include piroxicam, doxycycline, and various other poorly water-soluble drugs.

Q9: What types of modified beta-cyclodextrins are available? A: HP-β-CD (hydroxypropyl-beta-cyclodextrin) and SBE-β-CD (sulfobutylether-beta-cyclodextrin) are examples.