Cyclodextrins absorption enhancers

Marttin, E., Verhoef, J. C., and Merkus, F. W. H. M. 1998. Ef cacy, safety and mechanism of cyclodextrins as absorption enhancers in nasal delivery of peptide and protein dtdgsug Target. 6 17-36. 

Watanabe, Y., et al. 1992. Absorption enhancement of polypeptide drugs by cyclodextrins. I. Enhanced rectal absorption of insulin from hollow-type suppositories containing insulin and cyclodextrins in rabbits. Chem Pharm Bull 40 3042. 

Long-Acting Absorption-Enhancing Effects of Cyclodextrins.154... 

In this chapter, we especially focus on the strategies for enhancement of rectal absorption of various drugs including peptides and proteins from rectal mucosa using pharmaceutically useful excipients, cyclodextrins (CyDs), and the other absorption enhancers. 

Hovgaard, L., and H. Brondsted. 1995. Drug delivery studies in Caco-2 monolayers. IV. Absorption enhancer effects of cyclodextrins. Pharm Res 12 1328-1332. 

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]. 

Schipper, N.G.M., et al. 1993. Nasal insulin delivery with dimethyl- 3-cyclodextrin as an absorption enhancer in rabbits-powder more effective than liquid formulations. Pharm Res 10 682. 

Agerholm, C., et al. 1994. Epithelial transport and bioavailability of intranasally administered human growth hormone formulated with the absorption enhancers didecanoyl-L-alpha-phospha-tidylcholine and alpha-cyclodextrins in rabbits. J Pharm Sci 83 1706. 

Merkus, F.W., et al. 1991. Absorption enhancing effect of cyclodextrins on intranasally administered insulin in rats. Pharm Res 8 588. 

Ahsan, F., et al. 2001. Mutual inhibition of the insulin absorption-enhancing properties of dode-cylmaltoside and dimethyl-beta-cyclodextrin following nasal administration. Pharm Res 18 608. 

Consequently, absorption enhancers were used in dry powder and liquid formulations to enhance the pulmonary absorption of SCT. Without absorption enhancers, SCT absorption from dry powder or solution was similar to that observed after intratracheal administration. However, the absorption was more improved from dry powder than from solution when absorption enhancers (oleic acid, lecithin, citric acid, taurocholic acid, dimethyl-[5-cyclodextrin, octyl-P-D-glu-coside) were co-administered intratracheally. Such improved absorption could be due to the fact that enhancers added to the dry powder dissolved at high concentration because only a trace volume of fluid lining the alveolar epithelium was available for their dissolution. However, the potential implications of such a mechanism on lung toxicity, especially in lung edema, is yet to be investigated in detail [68]. 

Other interesting approaches to enhance drag absorption used cyclodextrins. They act as solubilizers of drags or alter the physical structure of administered proteins. 

The authors also studied the influence of the chain length of alkylmaltosides on the nasal absorption of enoxaparin. The results indicated that increases in the concentration of alkylmaltosides increased the AUC for plasma anti-factor Xa it was found that the absolute and relative bioavailabilities of enoxaparin increased by twofold with an increase in alkyl chain length from 8 to 14 carbons. Of all the alkylmaltosides, TDM was found to be the most potent absorption enhancer [85], Furthermore, we have also shown the efficacy of cyclodextrins in enhancing absorption following the nasal delivery of LMWHs. Three different cyclodextrins were employed P-cyclodextrins (P-CD), hydroxypropyl p-CD (FIPP-CD), and dimethyl P-CD (DM(5-CD). P-CD showed therapeutic levels of anti-factor Xa only at 2.5 and 5% p-CD, but there was no significant difference between the two concentrations, which was attributed to their solubility limit. In the case of HPP-CD, neither 1.25 nor 2.5% produced an appreciable increase in anti-factor Xa levels ... 

A study related to the buccal bioavailability of testosterone indicated the absorption enhancing effect of hydroxypropyl-p-cyclodextrine with a relative bioavailability of 165% versus the administration without absorption enhancers. This effect was probably due to an increased solubility of testosterone, although cyclodextrins might also extract lipids from the intercellular matrix.f In the same study, sodium tauro-24,25-dihydrofusidate and sodium deoxycholate did not show any enhancing properties. 

Alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems, including liposomes, cyclodextrins, and micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally [2]. 

Hermans WAJJ, Deurloo MJM, Romeyn SG, et al. Nasal absorption enhancement of 17 P-estradiol by dimethyl-P-cyclodextrin in rabbits and rats. Pharm Res 1990 7 500-503. 

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. 

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