Nasal devices

The lower vertebrates then possessed a useful nasal device which had already been utilised by their predecessors as a social chemical detector. Air breathing meant that their nasal air-flow was relatively weak in the absence of the pulling power exerted by lungs which... 

Nasal devices, such as metered-dose nasal sprays, are simple for the patient to use and might be expected to be more acceptable to the patient than the use of pessaries or suppositories for the intravaginal and rectal delivery routes respectively. 

The type of nasal device employed in delivering a drug formulation plays a major role in the efficacy of the treatment. In general, two types of delivery systems are used mechanical pumps and pressurized aerosol containers. The properties of the drug to be used influence the selection of the system. The various types of delivery devices are described in the following sections. 

Diazepam As mentioned earlier, because of shortcomings of rectal administration, the nasal delivery of diazepam has gained interest. The nasal bioavailability of diazepam in sheep was estimated and further compared with results obtained earlier in humans and rabbits [106] in this study, human and rabbit nasal bioavailability for the first 30min was reported to be 37 and 54%, respectively [113]. Diazepam solubilized in PEG 300 was used for nasal administration via a modified nasal device, a Pfeiffer unit dose (Princeton, NJ). The sheep received the nasal formulations in a fixed standing position such that the head was slightly tilted back. It was found that the serum concentration after administration of a 7-mg solution of diazepam was... 

Following the discussion in the section on Nasal Anatomy and Physiology , it is apparent that data on droplet size and spray angle from a nasal device are important for the regulatory authorities. This section reviews the types of nasal devices available, discusses clinical studies on spray angle and droplet size and reviews device testing. 

Figure 13.2 Cross-section of a traditional multidose nasal device.

Figure 13.3 Atypical unit-dose nasal device.

It should be assumed that the regulatory authorities will question as much, if not more, the nasal delivery device, rather than the formulation per se. They will critically examine for equivalence between the nasal device used in clinical trials and that proposed for the market. As the nasal device is usually more complicated in design than the formulation, and is manufactured by a third party, it is absolutely essential to work closely with the device provider. Among the key questions to ask of the supplier are the following ... 

The use of a bioadhesive, polymeric dosage form for sustained dehvery raises questions about swallowing or aspirating the device. The surface area is small, and patient comfort should be addressed by designing a small (less than 2 cm ), thin (less than 0.1 mm (4 mil) thick) device that conforms to the mucosal surface. The buccal route may prove useful for peptide or protein dehvery because of the absence of protease activity in the sahva. However, the epithelium is relatively tight, based on its electrophysiological properties. An average conductance in the dog is 1 mS/cm (57) as compared to conductances of about 27 and 10 mS/cm in the small intestine and nasal mucosa, respectively (58,59) these may be classified as leaky epitheha. 

In mart, an overlooked feature is the occurrence of mucoid-like plugs in the foetal nostrils (Schaeffer, 1910). The presence of this blockage can be confirmed by endoscopic inspection in utero these plugs seem likely to affect free amniotic flow, since they appear to be reinforced by a folded membranous gathering at the nasal vestibule (PI. 4B). A degree of restriction of fluid access to the VN aperture, which is immediately caudal to the nostril aperture, and is patent in foetal life, may be a protective feature (Jordan, 1972). The timing of the dissolution of these sealant devices prior to parturition is regrettably not known. 

Nasal spray Zolmitriptan 5, 10, or 20 mg at onset can repeat after 2 hours if needed Optimal dose is 20 mg maximum daily dose is 40 mg single-dose device delivering 5 or 20 mg administer one spray in one nostril... 

A number of means may be used to administer materials nasally, nebulizers and aerosol pumps being the most attractive first choices. Accurate dose administration requires careful planning, evaluation of the administration device, and attention to technique. 

Other delivery systems are transdermal patches, metered dose inhalers, nasal sprays, implantable devices, and needle-free injections. A description of needleless injection is given in Exhibit 5.16. 

Nicotine nasal spray is marketed as a pharmacy-only medication in the UK, and is available only by prescription in the USA. The nasal spray was designed to deliver doses of nicotine to the smoker more rapidly than other NRT products. The device is a multidose bottle with a pump that delivers 0.5 mg of nicotine per 50-pL squirt. Each dose consists of two squirts, one to each nostril. Nicotine from the nasal spray is absorbed into the blood more rapidly than from the gum (Schneider et al. 1996). Venous plasma concentrations after a single 1-mg dose range between 5 and 12 ng mL Time to peak plasma concentration (7j ax) with nasal administration is around 11-13 min for 1-mg doses. This rise time is slower than for cigarette delivery (Henningfield et al. 1993), but faster than for the other NRT products. 

Oral 25, 50, 100 mg tablets Nasal 5, 20 mg unit dose spray devices... 

---