Absorption cyclodextrin enhancement

Me, T., Arima, H., Abe, K., et al. (1992) Possible mechanisms of cyclodextrin-enhanced nasal absorption of peptide and protein dmgs. In Hedges, A.R. (ed.). Minutes of the 6th International Symposium on Cyclodextrins, pp. 503-508. Editions de Sante, Paris. 

Encapsulation within an enteric coat (resistant to low pH values) protects the product during stomach transit. Microcapsules/spheres utilized have been made from various polymeric substances, including cellulose, polyvinyl alcohol, polymethylacrylates and polystyrene. Delivery systems based upon the use of liposomes and cyclodextrin-protective coats have also been developed. Included in some such systems also are protease inhibitors, such as aprotinin and ovomucoids. Permeation enhancers employed are usually detergent-based substances, which can enhance absorption through the gastrointestinal lining. 

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. 

CYCLODEXTRINS AS MULTIFUNCTIONAL ENHANCERS FOR RECTAL DRUG ABSORPTION... 

Iwaoku, R., et al. 1982. Enhanced absorption of phenobarbital from suppositories containing phenobarbital-(3-cyclodextrin inclusion complex. Chem Pharm Bull 30 1416. 

Arima, H., et al. 1992. Enhanced rectal absorption and reduced local irritation of the antiinflammatory drug ethyl 4-biphenylylacetate in rats by complexation with water-soluble (3-cyclodextrin derivatives and formulation as oleaginous suppository. J Pharm Sci 81 1119. 

Uekama, K., et al. 1995. Modification of rectal absorption of morphine from hollow-type suppositories with a combination of a-cyclodextrin and viscosity-enhancing polysaccharide. 

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 ... 

Several studies have shown that combinations of cyclodextrins drug complexes and viscosity enhancers can significantly improved ocular absorption [141,236-237] and should therefore be further investigated. 

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