Cyclodextrin hydroxypropyl

Unfortunately, the relatively low solubility of /8-cyclodextrin has precluded its widespread use as a solubilizing agent. To enhance the solubility of /8-cyclodextrin, much work has been carried out on possible derivatizations of the /8-cyclodextrin skeleton. 2-Hydroxypropyl-/3-cyclodextrin has been found to exhibit the desired enhanced solubility, while still retaining the optimal binding characteristics of underivatized /8-cyclodextrin. In addition, this derivative is relatively nontoxic and may even be used in parenteral applications [63],... 

The enantioselective separation of racemic synthetic dihydrofurocoumarins in which the stereogenic center is located in the furan ring was accomplished by cyclodextrin-based LC <2003JCH(1011)37>. Hydroxypropyl-/3-cyclodextrin was the most effective chiral stationary phase, showing some enantioselectivity for 22 of the 28 dihydrofurocoumarins, and baseline resolving 16 of them in reversed-phase mode. 

Pitha J, et al. Hydroxypropyl- 3-cyclodextrin preparation and characterization, effects on solubility of drags. Int J Phann 1986 29 73. 

Hydroxypropyl-(3-cyclodextrin HP-(3-CyD Ri, R2, R3 = H or CH2CH(OH)CH3 Oral, parenteral, local... 

Another type of absorption enhancer, which has been shown to have a better safety profile, is cyclodextrin (CD) [39]. CDs have been shown to form inclusion complexes with lipophilic drugs, thereby improving their aqueous solubility and stability. A powdered insulin formulation containing dimethyl-(3-cyclodextrin improved the absolute bioavailability of insulin by 13% in rabbits compared to a control liquid formulation (1%) of insulin with dimethyl-(3-cyclodextrin [40]. Recently, hydroxypropyl (3-cyclodextrin has been shown to be more effective for enhancing the nasal absorption of acyclovir than a range of other absorption enhancers in vivo [41]. 

No toxicological effects of hydroxypropyl (3-cyclodextrins were observed on oral administration at doses up to 5000mg/Kg in rats and lOOOmg/Kg in rabbits.63 Intravenous administration was tolerated at doses of 200mg/Kg in rats and monkeys.64 Due to its high solubility, crystallization causing renal damage does not occur in the kidneys clearance occurs in about four hours.63... 

The solubility of a complex is generally greater than the solubility of the complexed compound, but less than the solubility of the cyclodextrin. If insufficient solubility has been achieved using unmodified cyclodextrins, greater solubility may be achieved with derivatives of cyclodextrins. Soluble derivatives, such as hydroxy-propyl-(3-cyclodextrin, can increase the solubility of insoluble drugs sufficiently to allow them to be administered parentally. Flunarizine, used to treat stroke victims, is very insoluble and, after oral administration, reaches therapeutic concentrations very slowly. When injected as a complex with hydroxypropyl-(3-cyclodextrin, a therapeutic concentration is achieved in the brain in minutes.78... 

Reer, O. Muller, B.W. The influence of cosolvents and surfactants on the complexation of dexamethasone with hydroxypropyl-(3-cyclodextrin investigated with a simplex lattice design. Eur. J. Pharm. Biopharm. 1993, 39 (3), 105-111. 

Solubilisation by surface-active agents is discussed in Chapter 6. Alternatives to micellar solubilisation (or solubilisation in vesicles) include the use of the cyclodextrin family. When the first edition of this book was published in 1981 (and a diagram of a cyclo-dextrin-dmg complex was used to adorn the cover), the use of cyclodextrins was in its infancy. Attention was then focused around a-, P- and yavailable commercially for pharmaceutical use. Ten per cent of this cyclodextrin can enhance the solubility of betamethasone 118 times, of diazepam 21 times and of ibuprofen 55 times. 

Chapter 8 - 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 bioavaUabibty 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-(3-cyclodextrin to levels in excess of 10 mg/mL which suggests Class I behavior (C). 

Uekama, K., Ikegami, K., Wang, Z. et al. Inhibitory effect of 2-hydroxypropyl-(3-cyclodextrin on crystal-growth of nifedipine during storage superior dissolution and oral bioavailability compared with polyvinylpyrrtolidone K-30. J. Pharm. Pharmacol 1992, 44, 73-78. 

Me, T., Abe, K., Adachi, H. et al. Potential use of 2-hydroxypropyl-(3-cyclodextrin in designing nasal preparations of insulin involving lipophilic absorption enhancer HPE-101. Drug Deliver. Syst. 1992, 7, 91-95. 

Ressing, M. E., Jiskoot, W., Talsma, H. et al. The influence of sucrose, dextran, and hydroxypropyl-(3-cyclodextrin as lyoprotect-ants for a freeze-dried mouse IgG2a monoclonal antibody (MN12). Pharm. Res. 1992, 9, 266-270. 

Wang, Z., Ikegami, K., Hirayama, F., Uekama, K. Release characteristics of nifedipine from 2-hydroxypropyl-(3-cyclodextrin complex during storage and its modification of hybridizing polyvinylpyrrolidone K-30. Chem. Pharm. Bull. 1993, 41, 1822-1826. 

Wang, Z., Hirayama, R, Uekama, K. Design and in vitro evaluation of a modified-release oral dosage form of nifedipine by hybridization of hydroxypropyl-(3-cyclodextrin and hydroxypropyl-cellulose. J. Pharm. Pharmacol. 1993, 45, 942-946. 

Cyclodextrin complexation (See Chapter 40) can also represent a way to improve the stability and the solubility of sensitive drugs such as thalidomide. Thalidomide is currently in clinical use for the treatment and prevention of graft-versus-host disease in leukemia patients after bone marrow transplant. However, this drug is sparingly soluble in aqueous solutions (50 Kig/mL) and is readily hydrolyzed. Complexation with hydroxypropyl (3-cyclodextrin increases the solubility to 1700 Kig/mL and extends the half-life of a dilute solution from 2.1 to 4.1 h. Other vulnerable and sparingly soluble drugs stabilized by means of cyclodextrin complexation are the non-steroidal antiinflammatory drugs diclofenac, piroxicam, and indomethacin and the anthra-cycline antibiotic daunorubicin. ... 

Tanaka, M., Y. Iwata, Y. Kouzuki, K. Taniguchi, H. Matsuda, H. Arima, and S. Tsuchiya. 1995. Effect of 2-hydroxypropyl-(3-cyclodextrin on percutaneous absorption of methyl paraben./. Pharm. Pharmacol. 47 897-900. 

Wang XJ, Brusseau ML. (1993). Solubilization of some low-polarity organic compounds by hydroxypropyl-/3-cyclodextrin. Environmental Science and Technology 27 2821-2825. 

Brewster, M. E., Estes, K. S., Bodor, N. An intravenous toxidty of smdy of 2-hydroxypropyl-3-cyclodextrin, a useful drug solubilizer, in rats and monkeys. Int. J. Pharm. 1990,59,231-243. 

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