Sulfobutylether- cyclodextrins

An Agilent 3D CE coupled to a Bruker Esquire 3(X)(F quadrupole ion trap (QIT)-MS with a sulfobutylether-cyclodextrin-ammonium acetate separation buffer at pH 6.9 is used to analyze TNT, TNB, RDX, HMX, and CL-20 [199]. CE coupled to a mass spectrometer with ESI enables better resolution than LC separation and thus enhanced identification of moderate polarity nitra-mine explosives and their degradation products from soil and water samples. 

Figure 3 Three CDs provide case studies of the development time of a new excipient. Abbreviations CD, cyclodextrin HP, hydroxypropyl SBE, sulfobutylether.

Figure 8 Effect of CD anionic substituents on the complexation of water-insoluble steroids. Abbreviations. SA, sulfonate SPE, sulfopropylether SBE, sulfobutylether CD, cyclodextrin. Source From Ref. 19.

Luna EA, et al. Isolation and characterization by NMR spectroscopy of three monosub-stituted 4-sulfobutylether derivatives of cyclomaltoheptaose ((3-cyclodextrin). Carbohydr Res 1997 299 111. 

Another commonly used cyclodextrin Capfi oiulfobutylether ofi-CD (SBE-ft-CD), is a polyanionicp-cyclodextrin derivative with a sodium sulfonate salt separated from the lipophilic cavity by a butyl ether spacer group, or sulfobutylether. BotfHBGPand sulfobutylether qf-CD (SBE-p-CD) are widely used cyclodextrins for solubility-enhancing purpose. 

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.

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

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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