Oral metered-dose inhalers

The systemic availability of inhaled budesonide has been measured in 15 healthy volunteers, using an open crossover design. Each subject was given three treatments, intravenous budesonide 0.5 mg, inhaled budesonide (from a metered-dose inhaler with a Nebuhaler) 1 mg (200 micrograms x 5) plus oral charcoal, and inhaled budesonide 1 mg without oral charcoal. The treatment order was randomized. The mean systemic availability of inhaled budesonide compared with intravenous budesonide was 36% with charcoal and 35% without charcoal, indicating that the absorption of budesonide from the gastrointestinal tract did not contribute to its systemic availability. Pulmonary deposition was 36% with charcoal and 34% without. When the inhaler was used incorrectly, that is, the canister was shaken only before the first of the five inhalations, systemic availability fell by 50%. This shows that the performance of each inhaler is very dependent on proper use (16). 

Pulmonary deposition efficiency depends on physicochemical characteristics, such as density of the aerosol or dry powder particles [33-35], Generally, particle diameters less than than 5 pm are required for efficient pulmonary delivery [36, 37], Pulmonary deposition also depends on the nature of the delivery device and differs between metered dose inhalers (MDIs). For example, pulmonary deposition expressed as the ratio of pulmonary versus total (pulmonary + oral) absorbed drug, ranged from 15-55% for a number of salbutamol devices and from 66-85% for drugs with lower oral bioavailabilities such as budesonide. 

G. Dickens, D. Wermeling, C. Matheney, W. John, W. Abramowitz, S. Sista, T. Foster, and C. S., Flunisolide administered via metered dose inhaler with and without spacer and following oral administration, J. Allergy Clin. Immunol. 103, S135 (1999) 703 S132 (1999). 

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. 

A 35-year old Caucasian man with AIDS and multiple opportunistic infections, including Mycobacterium kansasii and Mycobacterium avium complex (MAC) disease developed moderate to severe primary sensorineural hearing loss after 4—5 months of therapy with oral azithromycin 500 mg/day. Other medications included ethambutol, isoniazid, rifabutin, ciprofloxacin, co-trimoxazole, fluconazole, zidovudine (later switched to stavudine), lamivudine, indinavir, methadone, mod-ified-release oral morphine, pseudoephedrine, diphenhydramine, megestrol acetate, trazodone, sorbitol, salbutamol by metered-dose inhaler and nebulizer, ipratropium, and oral morphine solution as needed. Significant improvement of the hearing impairment was documented 3 weeks after drug withdrawal. 

In a randomized, double-blind study, 943 patients with chronic obstructive pulmonary disease were treated over 12 weeks with either inhaled salmeterol 42 micrograms bd via a metered-dose inhaler or oral modified-release theophylline bd, titrated to serum concentrations of... 

A significant portion of drug delivered by metered-dose inhaler (MDI) or dry powder inhalation (50-90%) reaches the GI tract. The overall amount depends on how much drug is deposited in the oropharynx and swallowed and how much pulmonary deposited drug is removed from the lung by mucociliary clearance, ultimately reaching the GI tract. The oral bioavailability of the drug (F),... 

Practicing physicians face daily the economic hardships faced by patients who must pay for medications from limited incomes. Patients with chronic diseases in particular are especially vulnerable. Patients with asthma and COPD often carry several metered-dose inhalers and also take oral anti-inflammatory medications as well. In addition, many have other problems, such as diabetes or... 

Sympathomimetics are available in inhaled, oral, and parenteral dosage forms. The preferred route of administration is by inhalation. The use of oral and parenteral /3-agonists in COPD is discouraged because they are no more effective than a properly used metered-dose inhaler (MDI) or dry-powder inhaler (DPI), and the incidence of systemic adverse effects such as tachycardia and hand tremor is greater. Administration of /32-agonists in the outpatient and emergency room settings via inhalers (MDIs or DPIs) is at least as effective as nebulization therapy and usually favored for reasons of cost and... 

Beclomethasone dipropionate Metered-dose inhaler (42 tg/puff) Metered-dose inhaler (250 tg/puff) Oral tablets (5, 10, 20 mg)... 

Combination bronchodilator therapy - This topic has been recently reviewed In chronic asthma, the combination of IB and fenoterol was more effective administered by a metered dose inhaler than salbutamol. Aerosol IB when administered concurrently with Inhaled fenoterol and oral oxtriphylline increased bronchodllation with no detectable additional side effects. Inhalation of IB followed by metaproterenol resulted in additive bronchodllation that was greater and longer lasting than IB alone, metaproterenol alone or metaproterenol followed by IB. ° Neither Inhaled terbutallne nor DSCG were very effective in cold air-induced bronchoconstriction whereas both drugs in combination were much more effective. The interaction of methylxanthlnes and B-agonists continues to be a subject of interest. An Increased Incidence of... 

Dickens GR, Wermeling DP, Matheny CJ, et al. Pharmacokinetics of flunisolide administered via metered dose inhaler with and without a spaoer devioe and following oral administration. Ann Allergy Asthma Immunol 2000 84 528-532. 

Not used orally available as metered-dose inhaler and 0.02%... 

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