Hydroxypropyl-/i-cyclodextrin

Fig. 17.15. Determination of the organic impurities (compounds 1-11) in le-vocabastine drug substance. Conditions 225 mM borate buffer, 2.16% w/v SDS + 1.3% w/v hydroxypropyl-/i-cyclodextrin + 10% v/v 2-propanol, pH = 9, 57 cm fused silica capillary (effective length 50 cm) x 75 pm I.D., injection 5 s at 35mbar, 50°C, detection UV 214 nm, current program 0-15min 75-130 pA, 15-40 min 130 pA, 40-60 min 130-200 pA. (a = auto zero).

The approach of CMPAs has also been used in thin-layer chromatography (TLC) for the chiral resolution of a variety of racemic compounds [100-110]. Lepri et al. [104,105] used BSA as a mobile phase additive for the chiral resolution of dansyl amino acids and other drugs by TLC. Armstrong et al. [101,102] used unde-rivatized and hydroxyethyl and hydroxypropyl /I-cyclodextrins for the chiral resolution of dansyl amino acids, alkaloids, and other compounds. Aboul-Enein... 

The highly water-soluble 2-hydroxypropyl-/i-cyclodextrin (2-HP-/1-CD) is a commercially useful general complexing agent. Inclusion complexes of poorly water-soluble Naproxen with 2-HP-/1-CD were useful to increase its solubility and dissolution rate, and resulted in an enhancement of bio-availability and minimized the gastrointestinal toxicity of the drug [69]. The water solubility of melatonin, which is an indole amide neurohormone, was also enhanced in a complex with 2-HP-/J-CD [70]. 

Itraconazole, a weakly basic (pIC 3.7) water-insoluble antifungal drug, is solubilized to 10 mg/mL using a combination of non-covalent complexation with 40% hydroxypropyl-/i-cyclodextrin (i.e., 400 mg/mL) in water and pH adjustment to 2 in Sporanox oral solution (Peeters, et al., 2002). The relative oral bioavailability of itraconazole from the oral solution is 149% ... 

Almost no influence of the methylated /i-cyclodextrin on the yield can be observed if no additional organic solvent (except for butadiene or the product) is used as the non-polar phase. With hydroxypropyl-jd-cyclodextrin a decreased yield is obtained and the phase separation is more difficult. If cyclohexane or n-octane is added as the non-polar solvent the conversion and the yield increase with increasing cyclodextrin concentration up to a concentration of about 2 mol % cyclodextrin based on butadiene. Because of the high viscosity of the solution no further improvement can be achieved using higher cyclodextrin concentrations. Lower yields are obtained by use of a-cyclodextrin as compared with the methylated j8-cyclodextrin. 

Zuo, Z., Kwon, G., Stevenson, B., Diakur, J., and Wiebe, L.I. Flutamide - hydroxypropyl-6-cyclodextrin complex formulation, physiccal characterization, and absorption smdies using the Caco-2 in vitro model. /. Pharm. Pharmaceut. Sci., 3(2) 220-227, 2000. 

Boudad, H., Legrand, P., I.cBas, G., Cheron, M., Duchene D., and Ponchel, G. (2001), Combined hydroxypropyl-beta-cyclodextrin and poly(alkylcyanoacrylate) nanoparticles intended for oral administration of saquinavir, Int. J. Pharm., 218,113-124. 

Szathmary, S.C. Seiler, K.U. Luhmann, I. Huss, H.J. Pharmacokinetic behavior and absolute bioavailabihty of hydroxypropyl P-cyclodextrin after increasing doses in volunteers. Minutes of the 5th International Symposium Cyclodextrin Duchene, D., Ed. Editions de Sante Paris, 1990, 535-540. 

Gerloczy, A. Antal, S. Szatmari, I. Muller-Horvath, R. Szejtli, J. Absorption, distribution and excretion of carbon-14 labeled hydroxypropyl P-cyclodextrin in rats following oral administration. Minutes 5th International Symposium on Cyelodextrins. Duchene, D., Ed. Editions de Sante Paris, 1990 507-513. 

Shaker, D.S. Ghanem, A.-H. Li, S.K. Warner, K.S. Hashem, F.M. Higuchi, W.I. Mechanistic studies of the effect of hydroxypropyl-P-cyclodextrin on in vitro transdermal permeation of corticosterone through hairless mouse skin. Int. J. Pharm. 2003, 253, 1-11. 

Figure 3. Predicted DCS classification of Itraconazole (A) as well as the effect of solubility on fraction absorbed (B). The Spider plot suggest good oral bioavailability at solubility values above 100 pg/mL. The solubility of itraconazole at neutral pH is estimated at 1 ng/mL. Itraconazole can be solubilized in 2-hydroxypropyl-p-cyclodextrin to levels in excess of 10 mg/mL which suggests Class I behavior (C). (See color insert after Index.)...

Figure 15.7. Effects of bufuralol-related soft drugs (19)on isoproterenol-induced tachycardia (i.v. bolus of 3.8 jLtmol/kg vebicle 10%DMSO in 30%hydroxypropyl j3-cyclodextrin) and resting heart rate (i.v. infusion, pmol/kg/min, R = Et 4 pmol/kg/min, esmoiol 20 pmol/kg/min vehicle0.9%NaCl) in rats. Data represent the means of at least three animals error hars were omitted for better visibility.

The effects of complexation and stabilization of 2, 3 -dideoxy-adenosine (I) with 2-hydroxypropyl-beta-cyclodextrin (II) were studied, and the results of kinetic studies and pKa determinations are reported. Although hydrolysis is 100% suppressed in both the protonated and neutral complexes, due to the small binding constants, the maximum stabilization attainable in a 0.1 M solution of II at 25 °C was approximately 5-fold at pH 5 and 2-fold at pH 2. Possible inclusion geometries are considered in an attempt to account for the kinetic data. 

Reddy and Maturi (2005) examined the feasibility of using electrokinetic remediation for the removal of mixed contaminants (i.e. mixtures of heavy metals and PAHs) from kaolin (low permeability soU). Likewise, different types of flushing solution were evaluated by a laboratory experimental program, including a cosolvent (n-butylamine), surfactants (3% Tween 80 and 5% Igepal CA-720), and a cyclodextrin (10% hydroxypropyl-j8-cyclodextrin or HPCD). It was reported that... 

Rodriguez-Perez, A.I., Rodriguez-Tenreiro, C., Alvarez-Lorenzo, C. et al. 2006. Sertaconazole/hydroxypropyl-beta-cyclodextrin complexation Isothermal titration calorimetry and solubihty approaches. 7 Pharm Sci. 95 1751-1762. 

Similarly, the volume of an injection should be less than 5 ini, or even better, not more than 2-3 ml, i.e.. sufficient to dissolve the necessary amount of drug in 2-3 ml of 40% HPBCD (=2-hydroxypropyl- 5-cyclodextrin) solution—800-1200 mg HPBCD can be used. In liquid formulations the use of CD derivatives in excess is possible. In the case of Prostavasin injection, the molar ratio of prostaglandin E] to otCD is 1 11 (20 pg... 

CTAB, cetyltrimethylammonium bromide EDTA, ethylenediaminetetraacelic acid LOQ, limit of quantitation LOD, limit of detection DM- -CD, dimethyl- -cyclodextrin HP-/i-CD, hydroxypropyl-/5-cyclodextrin. 

A.I.R. Perez, C.R. Tenreiro, C.A. Lorenzo, P. Taboada, A. Concheiro, and J.J.T. Labandeira, Sertaconazole/hydroxypropyl-6-cyclodextrin complexation Isothermal titration calorimetry and solubihty approaches,/. Pharm. ScL, 95 (8), 1751-1762, 2006. 

Evaluating the effect of hydroxypropyl cyclodextrine (HPCD) on phenan-threne solubilization and biodegradation, showing HPCD significantly increased the apparent solubility (i.e., the bio availability) of phenanthrene, having a major impact on the biodegradation rate of phenanthrene [193]. 

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