Hydroxypropyl-β-Cyclodextrin EP, USP-NF
Application: Solubilization and stabilization of drug substances
Technical name: Hydroxypropyl-β-Cyclodextrin (HP-β-CD)
CAS No: 94035-02-6
Empirical formula: C42H70O35 (C3H6O)x, x=7·MS
Molecular weight: -
Cyclodextrins (CDs) are oligosaccharides used as complexing agents to increase the water solubility of lipophilic compounds and bio-availability of medicinal products.
Due to their cyclic structure, cyclodextrins can form inclusion complexes when they interact with hydrophobic drug substances; as a result, they demonstrate higher aqueous solubility than that of comparable acyclic saccharides.
Cyclodextrins are made up of six, seven or eight dextrose units, forming α-, β-, and γ-Cyclodextrins respectively, with different cavity sizes. Cavity size is the major determinant for the suitability of cyclodextrins in complexations.
High aqueous solubility of drug substances
Formation of inclusion complexes
Bio-adaptability and multi-functional properties
Permeability through the biological membranes
The mechanism for the increased solubility of cyclodextrins is rooted in their ability to form non-covalent dynamic inclusion complexes in solution. High solubility can lead to high dissolution rates and greater oral bioavailability and stability of biopharmaceuticals with high or low permeability and low solubility, BCS Class II and IV drug substances.
Cyclodextrins can also lower the free concentration of the drug and therefore affect significantly the pharmacokinetics and pharmacodynamics of the active substance.
In addition, cyclodextrins can reduce or prevent gastrointestinal and ocular irritation, reduce or eliminate unpleasant smells or tastes, prevent pre-systemic drug-drug or drug-additive interactions within a formulation or help to convert oils and liquid drugs into microcrystalline or amorphous powders.
Cyclodextrins have multiple applications. A great number of different pharmaceutical products containing cyclodextrins are currently on the market worldwide, mostly tablets, aqueous parenteral solutions, nasal sprays and eye drop solutions.
Examples of the use of cyclodextrins in medicines on the European market are β-CD in Cetirizine tablets and Cisapride suppositories, and γ-CD in Minoxidil solution. Examples of the use of β-CD derivatives are SBE-β-CD in the intravenous antimycotic Voriconazole, and HP-β-CD in the antifungal Itraconazole, intravenous and oral solutions. In Germany and Japan there are infusion products on the market, containing Alprostadil (PGE1) with α-CD.
SBE-β-CD has been designed to maximize safety and optimize interaction with drug molecules to improve the solubility, stability, bioavailability or lessen volatility, irritation, smell or taste of the drug. For β-CD, which itself has a relatively low aqueous solubility, substitution of any of the hydrogen bond-forming hydroxyl groups, even by lipophilic functions, results in a dramatic improvement in the aqueous solubility of the SBE-β-CD derivative.
Examples of API formulations containing HP-β-CD, currently on the market*: Aripiprazole, Cisapride, Hydrocortisone, Indomethacin, Levosimendan, Mitomycin, Posaconazole (POS) and Florfenicol (veterinary drug)
* Information published in Nature Reviews Drug Discovery 3, 1023-1035 (2004).