Bioavailability, cyclodextrin complexes

Uekama, K., Fuginaga, T., Horayama, F., Otagiri, M., Yamasaki, M., Seo, H., Hashimoto, T., and Tsuruoka, M. 1983a. Improvement of the oral bioavailability of digitalis glycosides by cyclodextrin complexation. 

Kikuchi, M., F. Hirayama, and K. Uekama. 1987. Improvement of oral and rectal bioavailability of carmofur by methylated (3-cyclodextrin complexations. Inl J Pharm 38 191. 

Soliman, O.A. Kimura, K. Hirayama, F. Uekama, K. El-Sabbagh, H.M. El-Gawad, A.E. Hashim, F.M. Amorphous spironolactone-hydroxypropylated cyclodextrin complexes with superior dissolution and oral bioavailability. Int. J. Pharm. 1997,149 (1), 73-83. 

Tokumura, T., Nanba, M., Tsushima, Y. et al. Enhancement of bioavailability of cinnarizine from its p-cyclodextrin complex on oral administration with DL-phenylalanine as a competing agent. J. 

Uekama, K., Otagiri, M., Uemura, Y et al Improvement of oral bioavailability of prednisolone by p-cyclodextrin complexation in humans. J. Pharmacobio-Dynam. 1983, 6, 124-127. 

Uekama, K., Matsuo, N., Hirayama, F. et al. Enhanced bioavailability of acetohexamide by p-cyclodextrin complexation. Yakugaku. Zasshi 1980, 100, 903-909. 

Miyaji, T., Inoue, Y, Acarrurk, R et al. Improvement of oral bioavailability of fenbufen by cyclodextrin complexations. Acta Pharm. Nord. 1992, 4, 17-22. 

Horiuchi, Y, Kikuchi, M., Hirayama, F. etal. Improvement of bioavailability of menaquinone-4 by dimethyl-p-cyclodextrin complexation following oral administration. Yakugaku. Zasshi 1988,108, 1093-1100. 

Otagiri, M., Imai, T., Uekama, K. Enhanced oral bioavailability of anti-inflammatory drug flurbiprofen in rabbits by tri-O-methyl-p-cyclodextrin complexation. J. Pharmacobio-Dynam. 1982, 5, 1027-1029. 

T Loftsson. Increasing the cyclodextrin complexation of drugs and drug bioavailability through addition of water-soluble polymers. Pharmazie 53 733-740, 1998. 

Seo, H. and Uekama, K. (1989) Enhanced bioavailability of digoxin by y-cyclodextrin complexation evaluation for sublingual and oral administrations in human. Yakugaku Zasshi 109 778-782. 

Uekama, K., Horiuchi, Y., Kikuchi, M., et al. (1988) Enhanced dissolution and oral bioavailability of a-tocopheryl esters by dimethyl-P-cyclodextrin complexations. J. Incl. Phenom. 6 167-174. 

Jambhekar S, Casella R, Maher T, The physicochemical characteristics and bioavailability of indomethacin from y -cyclodextrin, hydroxyethyl-y -cyclodextrin and hydroxypropyl-y -cyclodextrin complexes, Int. J. Pharm. 2004 270 149-166. 

Garefa-Rodriguez, J. J., Torrado, J., and Bolas, F. (2001). Improving bioavailability and anthelmintic activity of albendazole by preparing albendazole-cyclodextrin complexes. Parasite, 8, S188-S190. 

In recent years publications of increasing numbers have been devoted to the enhancement of the solubility and bioavailability of hardly soluble drugs by cyclodextrin complexation /2-5/ Fendiline seemed to be an appropriate guest molecule for /2-cyclodextrin By the complexation of the drug a better solubility and enhanced bioavailability was expected ... 

Cyclodextrins have found particular application for the formulation of poorly water soluble, volatile, or unstable herbicides. Among the advantages of cyclodextrin complexes of pesticides are enhanced stabilization, reduced volatility, masked bad odor, enhanced wettability, solubility and bioavailability, and controlled release properties. Of the cyclodextrins, BCD is the only one available at a reasonid)le price, and its use may be economically feasible within a few years (. Several herbicides that have been frequently implicated in groundwater contamination (1-2) were selected as candidates for complexation with BCD in an attempt to develop formulations that could prevent entry of the chemical into the groundwater while maintaining effective weed control. 

Cyclodextrin complexation has been extensively applied to enhance the solubility, dissolution rate, membrane permeability and bioavailability of slightly soluble drugs [6-9]. 

A good deal of attention recently has been directed towards the use of derivatives of cyclodextrin for the solubilization and stabilization of pharmaceuticals [124 126]. One cautionary note—complexation may adversely affect the dissolution an/or permeability characteristics of the drug, thereby possibly decreasing drug bioavailability. 

Miyake, K. et al., Improvement of solubility and oral bioavailability of rutin by complexation with 2-hydroxypropyl-beta-cyclodextrin, Pharm. Dev. Technol, 5, 399, 2000. 

Nitroglycerine 10a is both a drug and an explosive. Its inclusion into the cavity of p-cyclodextrin, p-CD, 11 prevents its decomposition and enhances its bioavailability [14]. The complex of 10a with 11 is marketed under the name Nitropen as a coronary dilator sublingual tablets by Nippon Kayaku company in Japan. 

The bioavailability of silibinin from the extract is low and seems to depend on several factors such as (i) the content of accompanying substances with a solubilizing character such as other flavonoids, phenol derivatives, aminoacids, proteins, tocopherol, fat, cholesterol, and others found in the extract and (ii) the concentration of the extract itself (132,133). The systemic bioavailability can be enhanced by adding solubilizing substances to the extract (11,134). The bioavailability of silibinin can also be enhanced by the complexation with phosphatidylcholine or p-cyclodextrin, and possibly by the choice of the capsule material (135-137). The variations in content, dissolution, and (oral) bioavailability of silibinin between different commercially available silymarin products—despite the same declaration of content—are significant (138). 

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]. 

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