Use to enhance intranasal absorption

Bioadhesive agents, use to enhance intranasal absorption of peptides and proteins, 304... 

Table 9.5 Examples of some approaches used to enhance intranasal drug absorption...

Although, as described above, the vagina is permeable to many peptides and proteins, in most cases the bioavailability is insufficient for systemic therapy and is also highly variable. Penetration enhancers may be used to promote peptide absorption across the vaginal epithelium. However, less extensive investigations on the use of penetration enhancers for the vaginal route have been carried out in comparison to other routes, such as intranasal and transdermal (see Sections 9.7.1 and 8.6.1). 

Polyacrylic acid aqueous gel enhances the absorption of calcitonin after nasal as well as rectal administration. When [Asul,7]-eel calcitonin (lOU/kg) was administered nasally in polyacrylic acid gel at a concentration of 0.1% w/v, a prominent hypocalcemic effect was seen in the first 30min. Nasal administration of [Asul,7]-eel calcitonin in saline had no hypocalcemic effect at the same dose when given by the nasal route. In addition to this, the effect of [Asul,7]-eel calcitonin in the dose range of 1-10 U/kg has also been studied. The resulting data showed that a rapid reduction in plasma calcium concentrations can be achieved at doses of 5 and 10 U/kg however, at doses of 1 U/kg only a small reduction in the plasma calcium concentration was observed, suggesting that polyacrylic acid gel can be used for the intranasal administration of peptides such as calcitonin. The possible side effects, however, were not known at the time the study was performed [76-78],... 

Midazolam, Triazolam, and Flurazepam The feasibility of intranasal administration of midazolam, flurazepam, and triazolam has been studied and compared with oral absorption in dogs. There was a 3.4-fold increase in the Cmax after nasal administration, from 5.5-8.7ng/mL to 17.4-30.0 ng/mL. The mean tm showed comparable values for both routes. The Tnmx obtained after nasal administration of midazolam was found to be 15 min, as compared with the 15-45 min observed for oral dosing, while the Cmax after nasal administration was 6.5-20.3 ng/mL, as compared with 3.0-8.6ng/mL observed for the oral route. Like midazolam and triazolam, flurazepam also showed a shorter half-life, 15 min, as compared with 15 15 min with oral administration. The Cmax for oral administration was 0.14-0.59 ng/mL after nasal administration it was in the range of 2.6-11.1 ng/mL, a 16.4-fold increase. Since the gastrointestinal tract at bedtime is likely to be in the fed state, causing a twofold decrease in the absorption of midazolam and triazolam, the nasal route may be a better option for the treatment of amnesia, since these drugs cross the nasal mucosa effectively without the use of an absorption enhancer, as shown in these studies [108],... 

Lecithins are also used in suppository bases, to reduce the brittleness of suppositories, and have been investigated for their absorption-enhancing properties in an intranasal insulin formulation. Lecithins are also commonly used as a component of enteral and parenteral nutrition formulations. 

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]. 

Uptake via the nasal cavity to the brain, thereby bypassing the blood/brain barrier, can be improved using absorption enhancers and transporters such as chitosan nanoparticles.For example, Vaka and co-workers showed a 14-fold increase in rats in the bioavailability of intranasally administered NGF, a protein for the treatment of neurological diseases such as Alzheimer s, with chitosan compared to the formulation without chitosan. 

Nasal insulin delivery has been studied in several animal models, in vitro (Bechgaard et al, 1992 Maitani et al, 1992 Carstens et al, 1993) and in vivo using a plethora of different t es of promoters (Table IV). Intranasal insulin is better absorbed when administered as a spray than as drops (Pontiroli et al, 1987), and lyophilized insulin in an aerosol is more efficient than spray of an insulin solution (Nagai et al, 1984). As would be expected, large interspecies differences in the nasal absorption appear to exist, and enhancers differ substantially in efficacy and safety between species (Merkus et al, 1993). It is therefore extremely difficult to extrapolate absorption results obtained fi"om a particular animal study to humans. 

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