Metered solution inhaler

The metered solution inhaler (MSI), under development by Sheffield Pharmaceuticals, uses the same aerosolization principle as the AeroDose. The MSI is a portable, hand-held drug delivery device, as shown in Fig. 13. Using a motorized pump, drug solution is delivered to the surface of a ultrasonic horn powered... 

Fig. 13 The metered solution inhaler as shown in Sheffield Pharmaceutical s website (www.sheffieldpharm.com).

Hirst, P.H. Bacon, R.E. Newman, S.P. Armer, T. Mohsen, N. Pavkov, R. Byron, D. Deposition, absorption and bioavailability of aerosolized morphine sulfate delivered by a novel hand-held device, the metered solution inhaler (MSI). In Respiratory Drug Delivery VII Dalby, R.N., Byron, P.R., Parr, S.J., Peart, J., Eds. Interpharm Press, 2000 467 69. 

Ipratropium is the most commonly used anticholinergic for treating bronchoconstriction in asthma. It is available as an MDI and solution for nebulization. Ipratropium has an onset of action of approximately 30 minutes and a duration of action of 4 to 8 hours. Care should be taken not to spray the metered-dose inhaler into or allow the nebulized solution to get in the patient s eyes, as it can cause mydriasis and blurred vision. 

These agents are effective only by inhalation and are available as metered-dose inhalers cromolyn also comes as a nebulizer solution. 

Zainudin, B.M.Z., Biddiscombe. M., Tolfree, S.E.J., Short, M., and Spiro, S.G., Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurized metered dose inhaler, as a dry powder, and as a nebulized solution, Thorax, 45 469-473 (1990). 

Metered dose Inhaler-2 to 3 inhalations every 3 to 4 hours. Do not exceed 12 inhalations/day. Not recommended for children younger than 12 years of age. Inhalant solutions - Usually, treatment need not be repeated more often than every 4 hours to relieve acute bronchospasm attacks. In chronic bronchospastic pulmonary diseases, give 3 to 4 times/day. A single dose of nebulized metaproterenol in the treatment of an acute attack of asthma may not completely abort an attack. Not recommended for children younger than 12 years of age. 

Bronchospasm Hand-bulb Nebulizer 4 inhalations (range 3-7 inhalations) undiluted. Maybe repeated up to 5 times/day. Metered Dose Inhalation 1-2 inhalations q4h. Wait 1 min before administering 2nd inhalation. IPPB, Oxygen Aerosolization 0.5-1 ml of a 0.5% or 0.5 ml of a 1% solution diluted 1 3. 

Aerosol 200 dose metered-dose inhaler Solution for nebulizer 0.02%... 

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. 

Warren SJ, Farr SJ. Formulation of solution metered dose inhalers and comparison with aerosols emitted from conventional suspension systems. Int J Pharma 1995 124 195-203. 

Smyth HDC, Mejia-Millan EA, Hickey AJ. The effect of ethanol on solvency vapor pressure, and emitted droplet size of solution metered dose inhalers containing HFA 134a. Respir Drug Delivery VIII 2002 2 735-738. 

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. 

Harnor, K. J., Perkins, A. C., Wastie, M., et al. (1993), Effect of vapor pressure on the deposition pattern from solution phase metered dose inhalers, Int. J. Pharm., 95, 111-116. 

Smyth, H. D., Beck, V. P, Williams, D., and Hickey, A. J. (2004),The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers, AAPS PharmSciTech, 5, E7. 

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... 

Radiolabeling of nebulizer solutions, propellant-driven metered-dose inhalers, and dry-powder inhalers is... 

Surfactants are found in both solution and suspension formulations of metered dose inhalers (MDIs). The most common surfactants found in pressurised aerosol preparations include sorbitan trioleate (Span 85),... 

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. 

Raoult s law is important because it allows the calculation of vapour pressure from a knowledge of the composition of the solution. The requirement of the Montreal Protocol in 1989 for the replacement of chlorofluorocarbon (CFG) propellants in pressurised metered-dose inhalers with hydrofluoroalkanes (HFAs), because of the ozone-depleting... 

In general, and with a few rare exceptions (see below), the inhaled route of administration is the most difficult that is commonly encountered. Metered dose inhalers and nebulizers are considered together here because they are both aerosols of drug solution. 

In particular, the propellant-driven metered-dose inhalers release the aerosol cloud at the very high velocity caused by the pressure of the propellant. The open-mouth technique of inhalation [79] helps to slow down the droplets (and to evaporate the volatile excipients). An even more effective solution is to use spacer devices [4,79-87], in which the aerosol cloud can slowed down, the volatile constituents can evaporate, and any large particles will sediment out. Moreover, the patient can then inhale the remaining aerosol under optimal conditions for pulmonary delivery [4,8,56,79], that is, with a slow inspiratory flow rate. 

The most significant developments in metered-dose inhaler technology to occur since the early 1990s have been the introduction of hydrofluoroalkane (HFA) systems as alternatives to chlorofluorocarbon (CFC) systems [174]. This has largely been caused by the link between the use of CFC systems and ozone depletion in the upper atmosphere [152,175]. Albuterol and beclomethasone have been reformulated in HFA products, but as yet the CFC products are still subject to an annually renewable medical exemption. The Food and Drug Administration has recently published its position on alternative propellant formulations, which should initiate the phase-out of CFCs [176]. In the meantime, a number of generic CFC products of albuterol have been manufactured. The opportunity for reformulation of products as they come of patent is likely to increase research and development in this area in the near future. New formulation opportunities will also arise from these developments, including solutions [177], micellar [178,179], and microemulsion [180]. 

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