Lung deposition metered dose inhaler

A number of other peptide molecules are currently being explored for delivery via inhalation (6). Very recently, a much smaller peptide (leuprolide, about 9 amino acid residues) has been delivered by metered dose inhaler (MDI) in a characterized fashion to humans (7). This work revealed that about 50% of a dose deposited in the lung could be bioavailable. This value is much greater than those reported for nasal bioavailabilities of this and similar molecules (8). These results, and ours in the rat lung (9), imply that inhalation administration of some peptide and polypeptide molecules is perfectly feasible. 

To measure lung deposition by imaging, the aerosol must be first labelled or tagged with a suitable radionuclide. Radiolabelling techniques have been developed for current inhalation products including nebulizers, propellant-driven metered dose inhalers, and dry powder inhalers. 

Newman, S.P., Clark, A.R., Talaee, N., and Clarke, S.W., Pressurized aerosol deposition in the human lung with and without an open spacer device. Thorax, 44 706-710 (1989). Newman, S.P., Clark, A.R., Talaee, N., and Clarke, S.W., Lung deposition of 5 mg Intal from a pressurized metered dose inhaler assessed by radiotracer technique, Int. J. Pharm., 74 203-208 (1991). 

Hardy, J.G., Everard, M L., Coffiner, M., and Fossion, J., Lung deposition of a Nacystelyn metered dose inhaler formulation, J. Aerosol Med., 6 37-44 (1993). 

Hammermaier, A., Bidlingmaier, A., Waitzinger, J., Stechert, R., Wenske, H., and Jaeger, H., Radiolabelling of drugs in a metered dose inhaler (MDI) and lung deposition in human subjects, J. Aerosol Med., 7 173-176 (1994). 

Farr, S.J., Rowe, A.M., Rubsamen, R., and Taylor, G., Aerosol deposition in the human lung following administration from a microprocessor controlled pressurised metered dose inhaler. Thorax, 50 639-644 (1995). 

Thorsson L, Edsbacker S. Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer. Eur Respir J 1998 12(6) 1340-5. 

S. P. Newman, J. Brown, K. P. Steed, S. J. Reader, and H. Kladders, Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines Comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices, Chest 113 951 (1998). 

Patients who have difficulty in coordination with inhalers can use a spacer device. These remove the need for coordination between actuation of a pressurised metered dose inhaler and inhalation. The spacer device reduces the velocity of the aerosol and subsequent impaction on the oropharynx. In addition, the device allows more time for evaporation of the propellant so that a larger proportion of the particles can be inhaled and deposited in the lungs. The size of the spacer is important, the larger spacers with a one-way valve (Nebuhaler, Volumatic) being most effective. Spacer devices are particularly useful for patients with poor inhalation technique, for children, for patients requiring higher doses, for nocturnal asthma, and for patients who have poor coordination. 

Leach, C. L., Davidson, P. J., Hasselquist, B. E., and Boudreau, R. J. (2005), Influence of particle size and patient dosing technique on lung deposition of HFA-beclomethasone from a metered dose inhaler,./. Aerosol Med., 18, 379-385. 

Pitcairn, G, Reader, S., Pavia, D., and Newman, S. (2005), Deposition of corticosteroid aerosol in the human lung by respimat soft mist inhaler compared to deposition by metered dose inhaler or by turbuhaler dry powder inhaler, J. Aerosol Med., 18, 264-272. 

Adams, W.P. Poochikian, G. Taylor, A.S. Patel, R.M. Burke, G.P. Williams, R.L. Regulatory aspects of modifications to innovator bronchodilator metered dose inhalers and development of generic substitutes. J. Aerosol Med. Deposition, Clearance, and Effects in the Lung 1994, 7 (2), 119-134. 

Newman, S.P. Clark, A.R. Talaee, N. Clarke, S.W. Lung deposition of 5 mg Intal from a pressurized metered dose inhaler assessed by radiotracer technique. Int. J. Pharm. 1991, 74, 203-208. 

S. Affrime, M. Marino, M. Regional lung deposition of a technetium 99m-labeled formulation of mometasone furcate administration by hydrofluoroalkane 227 metered-dose Inhaler. Clin. Then 2000, 22 (12), 1483-1493. 

Of course, one-dimensional EDMs are not without their drawbacks. Indeed, they suffer from several of the same problems that plague empirical and onedimensional LDMs. In particular, their use of empirical mouth-throat deposition models is a serious drawback to modeling of dry powder and metered-dose inhalers, as discussed earlier with purely empirical models. As with onedimensional LDMs, the use of simplified lung geometries and empirical... 

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),... 

Hirst PH, Pitcairn GR, Weers JG, Tarara TE, Clark AR, Dellamary LA, Hall G, Shorr J, Newman SP. In vivo lung deposition of hollow porous particles from a pressurized metered-dose inhaler. Pharm Res 2002, 19, 258-264. 

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