Nasal spray metered-dose

Aerosols, Nasal Sprays, Metered-Dose Inhalers, and Dry Powder Inhalers Monograph. USP 29-NF 24 The United States Pharmacopoeia and The National Formulary The Official Compendia of Standards. Rockville, MD The United States Pharmacopeial Convention, Inc, 2006 2617-2636. 

United States Pharmacopoeia (2008) USP 30-NF 25 Aerosols, nasal sprays, metered-dose inhalers, and dry powder inhalers 601. ... 

In addition to the specialized tests, there are many other tests that are similar to those used for tablets and capsules. However, complexity of the sampling procedures required to perform the tests and details of the tests are beyond the scope of this chapter. So for further information, the reader is directed to consult the general chapter in the US Pharmacopeia on Aerosols, nasal sprays, metered-dose inhalers, and dry powder inhalers. ... 

Fomulationis) nasal spray 25 mg/metered dose inhaler with 0.25 mg/spray... 

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. 

Dosage - Each actuation of the nasal spray delivers a metered 50 mcL spray containing 0.5 mg nicotine. One dose is 1 mg of nicotine (2 sprays, 1 in each nostril). Start patients with 1 or 2 doses per hour, which may be increased up to a maximum recommended dose of 40 mg (80 sprays, somewhat less than >2 of the bottle) per day. For best results, encourage patients to use at least the recommended minimum of 8 doses/day, as less is unlikely to be effective. 

Aerosol 17 (freon-free), 18 mcg/puff in 200 metered-dose inhaler 0.02% (500 mcg/vial) for nebulization Nasal spray 21, 42 mcg/spray Tiotropium (Spiriva)... 

Inhalation drug products include inhalation aerosols (metered dose inhalers) inhalation solutions, suspensions, and sprays (administered via nebulizers) inhalation powders (dry powder inhalers) and nasal sprays. The CMC and preclinical considerations for inhalation drug products are unique in that these drug products are intended for respiratory tract-compromised patients. This is reflected in the level of concern given to the nature of the packaging components that may come in contact with the dosage form or the patient. 

Atrovent (ipratropium bromide) Nasal Spray 0.03% is a metered-dose, manual-pump spray unit that delivers 21 meg (70, uL ) ipratropium bromide per spray on an anhydrous basis in an isotonic, aqueous solution with pH... 

Nasonex nasal spray, 50 meg is a metered-dose, manual-pump spray unit containing an aqueous suspension of mometasone furoate monohydrate equivalent to 0.05% w/w mometasone furoate, calculated on the anhydrous basis, in an aqueous medium containing glycerin, micro-... 

Tri-Nasal spray is a metered-dose manual-spray pump in an amber polyethylene terephthalate bottle with 0.05% w/v triamcinolone acetonide in a solution containing citric acid, edetate disodium, polyethylene glycol 3350, propy-... 

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. 

Nasal sprays are available as squeeze bottles, which would not be expected to give reproducible dosing. They are also available as metered-dose devices, which would be expected to give more reproducible dosing, as a mechanical actuation delivers a pre-determined volume to the patient. Thus the dose of drag received by the patient will be dependent on the concentration of drag in the formulation. Commercial examples of metered-dose sprays include Syntaris, Beconase and Rhinocort which deliver flunisolide, beclomethasone and budesonide respectively. 

The volume of drug solution delivered to the nose also seems to have an effect on the bioavailability of the dmg. For example, the bioavailability of desmopressin was doubled when it was delivered as two 50 pi actuations from a metered nasal spray in comparison to the delivery of one 100 //I actuation. This may be attributed to prolonged retention of the dose at the administration site. 

As a nasal spray, flunisolide is effective in allergic rhinitis in clinical use [32-34], and their protective effects in patients with bronchial asthma have also been studied. The efficacy and safety of a new metered-dose inhaler of flunisolide has recently been reported [35]. 

Since the introduction of metered-dose inhalers, nasal solutions have increasingly been formulated as nasal sprays. Initially, aerosol-based systems containing chloro-fluorocarbons were employed however, the Montreal Protocol put an end to this. Thereafter, mechanical pumps or actuators were employed to deliver nasal formulations as sprays. These devices, using actuators, can precisely deliver as little as 25 pL and as much as 200 pL of a formulation. However, various factors must be considered in formulating the spray these include viscosity, particle size, and surface tension, all of which may affect the accuracy of the dose administered. 

Inhalation drug products, also referred to as orally inhaled and nasal drug products (OINDPs including inhalation aerosols and solutions, nasal aerosols and sprays), have a high likelihood of packaging component-dosage form interaction,and therefore have individual USFDA guidance documents. As an example, consider the metered dose inhaler (MDI), shown... 

Metered dose inhalers (MDIs) are pharmaceutical delivery systems designed for oral or nasal use, which deliver discrete doses of aerosolized medicament to the respiratory tract. The MDI contains the active substance, dissolved or suspended in a liquefied propellant system held in a pressurized container that is sealed with a metering valve. Actuation of the valve discharges a metered dose of medicament as an aerosol spray through an actuator during oral or nasal inhalation. 

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. 

Treatment of Migraine. Many years ago, ergotamine via metered dose inhaler was used successfully to treat migraine headache. I was made aware of this when I first became interested in medical aerosols by a senior professor of medicine who testified to its efficacy. More recently, sumatriptan nasal spray has been shown to provide significant relief of headaches [132]. 

Various studies (Bond et al. 1984 Newman et al. 1987a) have found droplet size distributions of aqueous nasal spray products to have mass mean (median) diameter values between 44 and 62 pun. These studies showed that the majority of the dose was deposited locally in the anterior one-third of the nose. The relationship between retention time and viscosity has shown that the addition of various concentrations of methylcellulose (MC) to a metered spray pump containing desmopressin resulted in a dose-related increase in mean particle size from 51 pan (0 percent MC) to 81 pan (0.25 percent MC) to 200 pirn (0.5 percent MC), without a change in mean spray weight. The longest retention time was observed for the 0.25 percent MC solution, which was attributed to its particle size (81 p,m) and not to an increase in viscosity, since a decrease in retention time was observed for the highest viscosity (0.5 percent MC) solution... 

Flunisolide nasal solution is available in an aqueous solubilized form, which delivers 25 pg per spray. The total daily adult dose for flunisolide from the nasal spray is 200 to 400 pg. Flunisolide inhalation aerosol for pulmonary delivery is a microcrystalline suspension in a chlorofluorocarbon propellant that delivers 250 pg per metered spray. The total daily adult inhalation dose for flunisolide is 1,000 pg. Doses exceeding 2,000 pg/day need to be monitored for FIFA suppression. 

In the US, two separate guidelines have been developed, one covering both metered dose inhalers (MDIs) and dry powder inhalers (DPIs) and one covering nasal sprays, inhalation solutions, and suspensions and inhalation sprays [22, 23], The guidance on MDIs and DPIs is however still in draft form nearly 10 years after being published for comment one of the unresolved issues is the dose content uniformity requirements which are discussed later in this chapter (Section 16.5.4). There are also other sections which would benefit from further discussion, in particular the number and nature of some of the tests that may be expected on stability. 

There are unique features pertaining to nasal sprays and inhalation products which make stability studies more complex and challenging. Examples include metering and spray production, energy required for spray production, the container closure system, and small doses. Critical attributes include the reproducibility (throughout the shelf-life) of the dose, the spray plume, and the particle/droplet size... 

Nasal spray Inhalation spray Inhalation solutions and suspensions Metered dose inhaler MDI Dry powder inhaler DPI, device metered Dry powder inhaler DPI, pre-metered Not included Non-pressurized metered dose nasal spray Nasal single use sprays Non-pressurized metered dose inhaler Product for nebuhzation (single and multiple use) Pressurized metered dose nasal sprays Pressurized metered dose inhaler Dry Powder Inhaler, device metered Nasal powders, device metered Dry Powder Inhaler, pre-metered Nasal drops (single and multiple use)... 

Stability test Nonpros surized metered dose nasal spray Nasal single use sprays Non-pressurized metered dose inhaler Product for nebulization (single and multiple use)... 

Stability test Pressurized metered dose nasal spray Pressurized metered dose inhaler Dry powder inhaler and nasal powders, device metered Dry powder inhaler pre-metered... 

Eor metered dose nasal sprays the pharmacopoeias are however different. The Ph. Eur. contains the same requirements as those for MDIs and DPIs, whereas the USP requirements are more challenging, as per those in the original FDA guideline for nasal sprays et al. 

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