Nasal drug delivery absorption enhancers

S. S. Davis and L. Ilium. Absorption enhancers for nasal drug delivery. Clin Pharmacokinet 42 1107-1128 (2003). 

Merkus, F.W.H.M., et al. 1993. Absorption enhancers in nasal drug delivery—Efficacy and safety. J Control Release 24 201. 

Marttin, E., J.C. Verhoef, and F.W. Merkus. 1998. Efficacy, safety and mechanism of cyclodex-trins as absorption enhancers in nasal delivery of peptide and protein drugs. J Drug Target 6 17. 

The nasal application of drugs is an area of growing interest (21) and a number of publications has shown that simple molecules as well as more complex species (eg calcitonin, insulin etc) can be well absorbed by this route, either directly or in the presence of so-called absorption enhancers. One problem with such materials could be too rapid clearance of the delivery system from the nasal cavity through the efficient action of the mucociliary system. For this reason Ilium has considered the use of microsphere systems. 

Chitosan is a linear cationic polysaccharide made up of copolymers of glucosamine and A-acetylglucosaminc. It is commercially obtained by alkaline deacetylation of chitin [53, 68] and has been used for the nasal delivery of a number of drugs. The usefulness of chitosan in the enhancement of nasal absorption was reported first by Ilium [69]. Later, Ilium and his group also published experimental results indicating that solution formulations with 0.5% chitosan promoted the absorption of nasally administered insulin in rat and sheep [70]. 

Kagatani et al. [90] studied the effect of acylcamitines as drug absorption enhancers for the nasal delivery of azetirelin in a rat model. A buffered azetirelin sample solution was administered intranasally, as described previously [47], The nasal and oral absorptions of azetirelin were then compared. The Fabs after nasal absorption was found to be 17.1%, which was 21 times greater than the 0.8% after oral administration. As reported above, a pilot study of oral azetirelin showed a bioavailability of about 2%. A bioavailability of about 20% was seen in the case of nasally administered TRH in humans as well as rats. The authors predicted that since azetirelin is an analog of TRH, its pharmacokinetic properties after nasal delivery in humans could also be about 20% [90,91]. 

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