Powder aerosolization

Pharmaceutical powder aerosols have more stringent requirements placed upon the formulation regarding moisture, particle size, and the valve. For metered-dose inhalers, the dispensed product must be deflvered as a spray having a relatively small (3—6 -lm) particle size so that the particles can be deposited at the proper site in the respiratory system. On the other hand, topical powders must be formulated to minimize the number of particles in the 3—6-p.m range because of the adverse effects on the body if these materials are accidently inhaled. 

S. C. Johnson Glade carpet powder, aerosol, soHd, electric, Hquid... 

MJ Clarke, MJ Tobyn, TN Staniforth. Physicochemical factors governing the performance of nedocromil sodium as a dry powder aerosol. J Pharm Sci 89(9) 11601-1169, 2000. 

Dry powder aerosols are more complicated to sample as the commercially available devices disperse the aerosol on the patient s inspiratory flow. In order to challenge the efficiency of these devices, it is important to sample at multiple flow rates. The standard flow rate has become 60 L/min. Additional flow rates of 30 (28.3) and 90 L/min have also been employed. Each impactor must be calibrated at the different flow rates employed. In recent compendial specifications the duration of sampling (4 s) and pressure drop across the device (4 kPa) has also been suggested. This corrects for the effort on the part of a patient in a single breath. 

CA Dunbar, AJ Hickey, P Holzner. Dispersion and characterization of pharmaceutical dry powder aerosols. KONA 16 7 14, 1998. 

NM Concessio, MM Van Oort, M Knowles, AJ Hickey. Pharmaceutical dry powder aerosols correlation of powder properties with dose delivery and implications for pharmacodynamic effect. Pharm Res 16 833-839, 1999. 

The DustGun aerosol generator, which has been reported for the delivery of aerosol particles to the IPL for toxicological evaluations [36], is another delivery technique which could be utilised for the evaluation of drug disposition after the delivery of pharmaceutical powder aerosols to the IPL. 

Performance and Regulatory Requirements describes various ways of characterizing the dry powder aerosols and provides information on product quality performance requirements and how these attributes must be reflected in registration applications. 

Venthoye, M.G., Characterization of an Amorphous Dry Powder Aerosol System, PhD Thesis, London University, 1997. 

Bell, J.H., Fisons Patent, Pelletised medieament formulations. Application no. 152047 (1975). Vidgren, M.T., Vidgren, P.A., and Paronen, T.P., Int. J. Pharm., 35 139-144 (1987). Chawla, A., Spray-dried Powders for Use in Dry Powder Aerosol Formulation, PhD Thesis, University of London, 1993. 

The standard mode of insulin therapy has traditionally been by subcutaneous injection using disposable needles/syringes. However, other routes of administration, including continuous subcutaneous insulin infusion pumps and inhalation of finely powdered aerosolized insulin, are currently being explored. 

Tolnaftate (Aftate, Tinactin) is available as a cream, solution, powder, or powder aerosol for application twice daily to infected areas. Recurrences following cessation of therapy are common, and infections of the palms, soles, and nails are usually unresponsive to tolnaftate alone. The powder or powder aerosol may be used chronically following initial treatment in patients susceptible to tinea infections. Tolnaftate is generally well tolerated and rarely causes irritation or allergic contact sensitization. 

Lucas P, Anderson K, Potter UJ, Staniforth JN. Enhancement of small particle size dry powder aerosol formulations using an ultra low-density additive. Pharma Res 1999 16(10) 1643-1647. 

Lucas P, Clarke MJ, Anderson K, Tobyn MJ, Staniforth JN. The role of fine particle excipients in pharmaceutical dry powder aerosols. Paper presented at Respiratory Drug Delivery VI, 1998. 

Smyth HDC, Garmise RJ, Cooney DJ, Zimmerer RO, Pipkin JD, Hickey AJ. Influence of physical form of Captisol particles on performance as a dry powder aerosol carrier. Paper presented at Respiratory Drug Delivery IX, Palm Desert, California, 2004. 

Tolnaftate Aftate Tinactin many others Aerosol powder aerosol solution powder solution Tinea (ringworm) infections... 

Such small particles usually are generated by air-jet micronization and less frequently by controlled precipitation or spray drying. As bulk powder, they usually tend to be very cohesive and exhibit poor flow and insufficient dispersion because of large interparticle forces such as van der Waals and electrostatic forces (Zeng et al. 2001 Podczeck 1998 Hickey et al. 1994). The control of sufficient powder flow and deaggregation (dispersion) is thus of utmost importance to ensure efficient therapy with a dry-powder aerosol. Two different formulation approaches are used currently in marketed DPI preparations to fulfill the requirements. Most often, coarse particles of a pharmacologically inactive excipient, usually a-lactose monohydrate, are added that act as a carrier and provide sufficient powder flow to the mixture. Other carbohydrates, amino acids, and phospholipids have been suggested frequently (Crowder et al. 2001). 

Clarke, M. J., Layzell, G., Tobyn, M. J., and Staniforth, J. N. The role of fine particle lactose in agglomerated dry powder aerosol formulations. J. Pharm. Pharmacol. 50(suppl) 186, 1998. 

Kassem, N. M., and Ganderton, D. The influence of carrier surface on the characteristics of inspirable powder aerosols. J. Pharm. Pharmacol. 42(suppl) llP, 1990. 

Tolnaftate (Aftate, Tinactin, and others) is available in a 1% concentration as a cream, gel, powder, aerosol powder, and topical solution, or as a topical aerosol liquid. 

In order to overcome the inherent problem associated with pulmonary aqueous solution and dry powder aerosols, Choi et al. [2] developed an ethanol suspension of insulin for inhalation, in which the solid insulin is suspended in ethanol and aerosolized with a commercial compressor nebulizer. The aerosol insulin particles were found to be 1.5 pm, with a geometric standard deviation of 1.3 pm. Exposure of rats to 10 mg/mL insulin aerosol resulted in a drastic fall in blood glucose and a marked rise in serum insulin level. The bioavailability of insulin/ethanol aerosol was 33% relative to SC injection, and comparable to that of insulin aerosols in aqueous solution and dry powder form. No acute toxic effects were detected in the rat lungs or airways [2]. 

These devices permit the drug to be delivered to the airways as a dry powder aerosol. All currently available DPIs are breath-actuated, thus the respirable cloud is produced in response to the patient s effort. DPIs therefore have the following advantages over pMDIs ... 

New DPI designs are numerous, with the novelty often associated with the technique for achieving powder aerosolization. Some of the recent patented devices incorporate an additional energy source to supplement the inspiratory force of the patient, in order to aerosolize the drug particles into the inhaled airstream. However, unless the addition energy source is breath activated (e.g. as in Spiros), such devices will be limited by the coordination difficulties typical of the pMDIs. 

Zeng, X. M., Pandhal, K. H., and Martin, G. P. (2000),The influence of lactose carrier on the content homogeneity and dispersibility of beclomethasone dipropionate from dry powder aerosols, Int. J. Pharm., 197,41-52. 

This review captures some of the most recent technologies with examples relating to pharmaceutical dry powder aerosol delivery. 

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