Sulfobutylether P-cyclodextrin

P-Cyclodextrin sulfobutylether, sodium salt Captisoh, (SBElyn,-beta-CD SBE7-P-CD SBECD sulfobutylether-P-cyclodextrin, sodium salt. 

Note the substitution pattern is random, yielding a heterogeneous mixture both in terms of the site of substitution as well as degree of substitution. The n value is an average number derived from the average degree of substitution. 

Cyclodextrins are crystalline, nonhygroscopic, cyclic oligosaccharides derived from starch see Cyclodextrins). Sulfobutylether P-cyclodextrin is an amorphous, anionic substituted P-cyclodextrin derivative (see Section 8) other substituted cyclodextrin derivatives are also available see Section 17). 

Sulfobutylether P-cyclodextrin can form noncovalent complexes with many types of compounds including small organic molecules, peptides, and proteins. It can also enhance their solubility and stability in water. The first application of sulfobutylether P-cyclodextrin was in injectable preparations it can also be used in oral solid and liquid dosage forms, and ophthalmic, inhalation, and intranasal formulations. Sulfobutylether P-cyclodextrin can function as an osmotic agent and/or a solubilizer for controlled-release delivery, and has antimicrobial preservative properties when present at sufficient concentrations. 

Sulfobutylether P-cyclodextrin occurs as a white amorphous powder. 

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Several new excipients are being evaluated in order to increase the solubility or improve the stability of parenteral drugs. Cyclodextrins have been tried for the above reasons. Currently, there are two FDA approved parenteral products that have utilized a and y-cyclodextrins. p-cyclodextrin is unsuitable for parenteral administration because it causes necrosis of the proximal kidney tubules upon IV and subcutaneous administration. Hydroxypropyl p-cyclodextrin (HPpCD) and sulfobutylether p-cyclodextrin (SBE-7-p-CD) have shown the most promise. Captisol is the trade name of SBE-7-p-CD and is anionic. Currently, two CaptisoF based small molecule IV and IM drug formulations are in Phase III clinical trials in the United States. One parenteral formulation that utilizes HPpCD (Cavitron ) is in Phase II/III clinical trials, and another (Sporanox) has been approved by... 

Fig. 5 CPMAS NMR spectra of (A) bulk prednisolone acquired with 2-msec contact time. (B) Physical mixture of 7.7% prednisolone in sulfobutylether P-cyclodextrin (Captisol) acquired with a 2-msec contact time. (C) Physical mixture of 7.7% prednisolone in sulfobutylether P-cyclodextrin (Captisol) acquired with a 15-msec contact time. (From Reft f)...

Table 13. SBE-p-CDs, have also shown good com-plexation characteristics. Table 14 shows the solubility enhancement for some selected compounds in a solution of Sulfobutylether p-cyclodextrin TV. The selected data given in Tables 13 and 14 provide a good illustration of the practical range of solubilization that can be achieved by complexation.

Excipient Spray-dried sulfobutylether p-cyclodextrin sodium... 

Sulfobutylether P-cyclodextrin is stable in the solid state and should be protected from high humidity. It should be stored in a tightly sealed container in a cool, dry place. 

The preservative activity of benzalkonium chloride is reduced in the presence of sulfobutylether P-cyclodextrin. 

Sulfobutylether P-cyclodextrin is prepared by alkylation of P-cyclodextrin using 1,4-butane sultone under basic conditions. The degree of substitution in P-cyclodextrin is controlled by the stoichiometric ratio of P-cyclodextrin to sultone used in the process. 

Sulfobutylether P-cyclodextrin is derived from P-cyclodextrin, which is toxic when administered parenterally (see Cyclodex-trins). However, studies have shown that sulfobutylether P-cyclodextrin is well tolerated at high doses, when administered via intravenous bolus injections, orally, and by inhala-tion. Up to 9 g/day may be administered by IV infusion in a licensed voriconazole formulation. ... 

Sulfobutylether P-cyclodextrin has been subjected to an extensive battery of in vitro and in vivo genotoxicity and pharmacological evaluations. No genotoxic or mutagenic changes were observed with sulfobutylether P-cyclodextrin administration. Sulfobutylether P-cyclodextrin is biocompatible and exhibits no pharmacological activity. It is rapidly eliminated unmetabolized when administered intravenously. 

Sulfobutylether P-cyclodextrin is included in IV and IM injectable products currently approved and marketed in the USA and Europe. It is included in the FDA inactive ingredient guide for IM and IV use. Its use by other routes, including oral, inhalation, and ophthalmic, is being evaluated in clinical studies. 

Figure 2 Moisture sorption-desorption isotherm of sulfobutylether P-cyclodextrin sodium, at 30°C.

Sulfobutylether P-cyclodextrin is stable in aqueous solutions at values above about pHl. It can degrade in highly acidic (pH < 1) solutions, particularly at elevated temperatures producing the ring-opened form, followed by hydrolysis of the a(l- 4) glucoside bonds. 

In addition to its use in pharmaceutical formulations, sulfobutylether P-cyclodextrin is also used in chromatographic separations, particularly in chiral separations by HPLC " and capillary electrophoresis and in tissue imaging. ... 

DBTHS, disodium 5,13-his(dodecyloxymethyl-4,7.11,14-tetraoxa-l,17-heptadecanedisulfonate ITP, isotachophoresis m-HEC, methyl-hydroxyethylcellulose PVP, polyvinylpirrolidone PSDVB, polystyrene-divinylbenzene copolymer SB-P-CD, sulfobutylether-p-cyclodextrin CAR-PDMS, carboxen-polyfdimefhylsiloxane) ESI-IT-MS, electrospray ionization ion trap-mass spectrometry CHES, 2-(V-cyclohexylamino)-ethanesulphonic acid CAPS, 3-(cyclohexylamino)-l-propanesttlfonic acid PHWE, pressurized hot water extraction ICP-MS, inductively coupled plasma-mass spectrometry SPME, solid-phase microextraction SPE, solid-phase extraction. 

TTAOH, tetradecyltrimethylammonium hydroxide ESI-IT-MS, electrospray ionization ion trap mass spectrometry SB- -CD, sulfobutylether-p-cyclodextrin PHWE, pressurized hot water extraction FPD, flame photometric detector SPE, solid-phase extraction MES, 2-[morphine]ethanesulphonic acid DDAOH, didodecyldimethylammonium hydroxide. 

Chitosan/sulfobutylether-p-cyclodextrin NPs Ocular drug delivery [260]... 

Mahmoud AA, El-Feky GS, Krunel R, Awad GEA. Chitosan/sulfobutylether-P-cyclodextrin nanoparticles as a potential approach for ocular drug delivery. Int J Pharm. 2011 413(l-2) 229-36. 

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