Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

4. Compounding of nasal midazolam preparations
Figure 4-3 : Optimal cyclodextrin concentration. Jarho et
al. demonstrated exceeding cyclodextrin concentration to
impair permeation of drug through cornea of pigmented
rabbits. Figure modified after [Jarho et al. 1996].
Permeation of drug molecules from aqueous cyclodextrin containing vehicles through semipermeable
membranes follows the same pattern as permeation through lipophilic biomembranes
[Loftsson et al. 2002]. Determination of drug fluxes through semi-permeable membranes have
been used to characterize release of drugs from cyclodextrin containing vehicles as well as to
assess stability constants of drug-cyclodextrin complexes [Masson et al., 1999; Ono et al., 1999].
4.3.3 Cyclodextrins in transmucosal nasal drug delivery
In nasal formulations, cyclodextrins are used to increase the aqueous solubility of lipophilic drugs.
However, cyclodextrins can also interact with biological membranes, acting as penetration
enhancers, especially in nasal delivery of peptides [Marttin et al., 1998]. Numerous studies have
demonstrated that methylated cyclodextrins are efficient absorption enhancers, and therefore well
established in nasal drug delivery [Merkus 1999]. The first cyclodextrin-based nasal formulations
contained steroidal hormones and peptides. The results were promising and the most effective
cyclodextrins, methylated cyclodextrin derivates, increased the bioavailability of progesterone
threefold with suspension of the same compound [Hermens et al., 1990; Matsubara et al. 1995;
van den Berg et al. 2004]. The estradiol nasal spray Aerodiol ® (Servier S.A, Meyrin Switzerland).
represents the successful use of cyclodextrins in nasal applications.
Katja Suter-Zimmermann Page 37 of 186 University of Basel, 2008