Nasal administration devices

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. 

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. 

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... 

As various types of devices for nasal administration, such as unit dose containers, metered dose sprays, compressed air nebulizers, and so on, are becoming available, formulation research should be conducted while considering a dosing device. 

Nasal preparations are supplied in multidose or singledose containers, provided, if necessary, with a suitable administration device, which may be designed to avoid contamination. 

Constraints on nasal delivery include a restricted capacity (i.e., the volume of formulation that can be delivered is limited), attainment of dose accuracy, and the reproducibility of delivery. The distribution of drug in the nasal cavity is highly dependent on the delivery device, formulation, and administration technique. In turn, the distribution of drug will affect permeability, residence time, and metabolism in the nasal cavity. 

Lately, the nasal route is receiving attention for the management of postoperative pain. Mucosal administration requires only a 1.1-1.5 times higher dose of fentanyl than the intravenous dose. ° For this new application field, called PCINA (patient-controlled-intranasal-analgesia), the pharmaceutical industry demands safety precautions of the delivery device, which can be fulfilled through implementation of intelligent microelectronic features. 

The site of drug deposition in the nasal cavity highly depends on the method of administration. When administering solution formulation, it is important to consider the particle/droplet size. In addition, the limitation is that the entire dose must be given in a volume of 25-200 pL, depending on the formulation. Nasal drops are the simplest and most convenient form. However, the exact volume of dosing is difficult to determine, which may be a device-related matter, and rapid drainage from the nose is another problem with drops. 

Pulmonary delivery of drugs is the administration route of choice in respiratory diseases such as chronic obstructive pulmonary disease and asthma. Different devices are available, including metered-dose inhalers, dry powder inhalers, and nebulizers, and nearly 80% of asthmatic patients worldwide use metered dose inhalers (1). Chlorofluorocarbons have been used as an aerosol propellant in metered-dose inhalers however, they deplete the ozone layer and are being replaced by more environment-friendly propellants, even though the contribution of aerosols of this type to the total global burden of chlorofluorocarbons is less than 0.5%. The first chloro-fluorocarbon-free metered-dose inhaler for asthma treatment was approved by the FDA in 1996 (2) and the European Union has set 2005 as a target date for the withdrawal of all chlorofluorocarbon-based inhalers (1). In the USA, prescriptions for chlorofluorocarbon-free medications rose from 16.4 million in 1996 to 33.8 million in 2000 (2). Most of the chlorofluorocarbon-free medications were steroids for nasal use (27.2 million). However, chlorofluorocarbon-containing medications stiU represented two-thirds of all prescriptions and increased from 63.0 to 67.6 million dispensed (2). 

Microspheres prepared from hyaluronan esters have been evaluated for the vaginal administration of calcitonin in the treatment of postmenopausal osteoporosis. Microspheres prepared from hyaluronan esters have also been used experimentally as delivery devices for nerve growth factors, and as a nasal delivery system for insulin. ... 

An alternative to the pulmonary route of administration is the nasal route, which is less demanding when it comes to formulation. With regard to, for example, particle size and simpler device development (5,90), examples are Minirin (Ferring), desmopression, and Suprecur (Sanofi-Aventis), buserelin, which are proteins formulated as nasal drops or nasal spray, where bioavailabdities of approximately 3% to 10% can be obtained. The formulations are just protein dissolved in purified water containing preservatives chlorbutanol and benzalkonium chloride (91,92). However, more advanced delivery systems are also used, for example, chitosan formulations where bioavailabihties of 14% to 15% compared to subcutaneous administration can be obtained (90). A recent review by nium (2007) gives more details on nanoparticulate systems used for nasal delivery (93) or consult Costantino et al. (2007) on the physiochemical and therapeutic aspects (5). 

The delivery of freeze-dried preparations can be performed by different routes oral, nasal, anal, pulmonary, transdermal and parenteral. Of these routes, some do not require any treatment of the drug before it is administered, e.g. in the form of powders or tablets or in inhaling devices. For parenteral administration, however, whether by injection or infusion, the freeze-dried cake must be returned to a liquid state, a process referred to as reconstitution . The main vehicle will normally consist of water for injection or a solution, the concentration of which will establish isotonicity. The time required for the complete dissolution of the cake may in some cases be critical and should therefore be known. 

In general, retention of the product within the nasal cavity will be attained if the vast majority of the particles or droplets are larger than 10 pm. The deposition site of the formulation is important and therefore also the container and dosing device and the way of administration. When using a spray the solution is finely distributed in the anterior part of the nose and mucociliary clearance causes the formulation to... 

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