From the Guidelines
Cyclodextrins are a crucial component in the formulation of certain antifungal medications, including itraconazole and voriconazole, enhancing their solubility and bioavailability. The use of cyclodextrins in pharmaceuticals is supported by substantial evidence, with hydroxypropyl-beta-cyclodextrin (HPβCD) being FDA-approved as a solubilizing agent in several medications 1. For instance, HPβCD is used in the formulation of itraconazole (Sporanox) and voriconazole (Vfend), which are used to treat various forms of candidiasis. The mechanism of action of cyclodextrins involves forming host-guest complexes with lipophilic drug molecules, allowing for improved drug delivery across biological barriers 1.
Some key points to consider when using cyclodextrin-based therapies include:
- Potential nephrotoxicity at high parenteral doses
- Variable effects depending on the specific cyclodextrin type and administration route
- Importance of careful consideration when implementing cyclodextrin-based therapies, especially in patients with significant renal dysfunction 1
- The need for dosage adjustment in patients with renal insufficiency, as seen with voriconazole, which requires a dose reduction in patients with creatinine clearance <50 mL/minute 1
In terms of specific applications, cyclodextrins have shown promise in clinical trials for the treatment of Niemann-Pick Type C disease, with HPβCD (VTS-270) demonstrating slowed neurological disease progression at doses of 900-1200 mg intrathecally every 2-4 weeks 1. Additionally, sulfobutylether-β-cyclodextrin (Captisol) is used in remdesivir formulations, highlighting the versatility of cyclodextrins in pharmaceutical applications.
Overall, the use of cyclodextrins in antifungal medications is supported by strong evidence, and their potential benefits and risks must be carefully considered in clinical practice.
From the Research
Cyclodextrin Properties and Applications
- Cyclodextrins are cyclic oligosaccharides that can improve the solubility and bioavailability of poorly soluble drugs 2
- They have a favourable toxicological profile, low local toxicity, and low mucous and eye irritability, making them virtually non-toxic when administered orally 2
- Cyclodextrins can be used as excipients in drugs delivered by oral, ocular, dermal, nasal, and rectal routes 2
Solubility Enhancement
- Cyclodextrins can form non-covalent dynamic inclusion complexes with poorly water-soluble drugs, increasing their apparent water solubility 3
- The formation of ternary complexes with cyclodextrins and water-soluble polymers can further enhance the solubility and dissolution behaviour of poorly soluble drugs 4
- Cyclodextrins can also form non-inclusion based complexes, aggregates, and stabilize supersaturated drug solutions, contributing to their solubilizing attributes 3
Pharmaceutical Applications
- Cyclodextrins have been used to improve the bioavailability of various drugs, including itraconazole 4 and posaconazole 5
- They have been incorporated into various pharmaceutical products, including oral formulations, intramuscular injections, and ready-to-use injection systems 6
- Cyclodextrin-based products have reached the market, taking advantage of their ability to camouflage undesirable physicochemical properties 3
Recent Developments
- New cyclodextrin derivatives, such as CD-based polyrotaxanes, CD-polymer conjugates, and thiolated CDs, are being developed to create innovative new drug delivery systems 6
- These derivatives exhibit properties such as cellular uptake enhancement, sustained drug release, and mucoadhesive properties, which can improve the efficacy and safety of drugs 6