Hydroxypropyl betadex

• BPHydroxypropylbetadex
• Ph. Eur.Hydroxypropylbetadex
• USP–NFHydroxypropyl Betadex

Cavasol W7 HP; HPβCD; 2-hydroxypropyl-β-cyclodextrin; hydroxypropyl-β-cyclodextrin; Kleptose HPB; Trappsol HPB

Cyclomaltoheptaose, 2-hydroxypropyl ether (partially substituted β-cyclodextrin) · [128446-35-5]

C42H70O35·(C3H6O)x · ≈ 1400 (depends on molar substitution)

Solubilising agent

Typical concentrations: — · Dosage forms: Liquid, Sterile (parenteral/ophthalmic)

Used to increase the aqueous solubility, stability and bioavailability of poorly soluble drugs by forming non-covalent inclusion complexes. It is used in oral solutions and solid dosage forms, parenteral products (intravenous and intramuscular), and ophthalmic, nasal and topical preparations; concentrations range from a few per cent to about 40% w/v in some oral and parenteral solutions. It can also mask taste and reduce irritation caused by some drugs.

A white or almost white, amorphous or crystalline, hygroscopic powder, practically odourless and with a slightly sweet taste. It is a mixture of β-cyclodextrin derivatives with different numbers and positions of hydroxypropyl groups.

Molar substitution

0.40–1.50 (Ph. Eur.); commercial parenteral grades typically about 0.6–0.9

Solubility

very soluble in water (more than 50% w/v) and in propylene glycol; freely soluble in methanol and ethanol

Cavity diameter

≈ 0.6–0.65 nm (as for β-cyclodextrin)

Physical form

amorphous; does not crystallise readily from solution

Stable in the solid state when protected from high humidity; store in a well-closed container in a cool, dry place. Aqueous solutions are stable and can be autoclaved, but the glycosidic bonds are hydrolysed by strong acids at elevated temperature.

Can form inclusion complexes with other formulation components, for example antimicrobial preservatives such as parabens and benzalkonium chloride, and so reduce their effectiveness. Strong oxidising agents should be avoided.

Produced by reacting β-cyclodextrin with propylene oxide in alkaline aqueous solution; the reaction conditions control the degree of substitution. The product is neutralised, purified (for example by dialysis or ion exchange) and spray- or freeze-dried.

Well tolerated orally and parenterally. After oral use it is very poorly absorbed and is fermented in the colon; high oral doses can cause soft stools or diarrhoea. After intravenous administration it is excreted unchanged by the kidneys and is much less nephrotoxic than parent β-cyclodextrin. The EMA has published guidance on cyclodextrins with dose thresholds for labelling.

Observe normal precautions for the quantity handled; eye protection, gloves and a dust mask are recommended.

Included in the FDA Inactive Ingredient Database (intravenous and intramuscular injections; oral solutions and tablets) and in parenteral and non-parenteral medicines licensed in Europe.

Alfadex; betadex; gamma cyclodextrin; sulfobutylether β-cyclodextrin (betadex sulfobutyl ether sodium).

The solubilising effect depends on the fit of the drug in the cavity and on the degree of substitution, so phase-solubility studies are needed for each drug. Using more cyclodextrin than required can reduce absorption by keeping the drug in the complexed form, and dilution after administration releases the drug rapidly.