Pharmaceutical powder aerosols

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. 

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. 

Chan, H.K., What is the role of particle morphology in pharmaceutical powder aerosols . Expert Opin. Drug Deliv., 2008,5, 909-914. 

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. 

Dusts, Mists, Aerosols and Fumes. The P-5 Digital Dust Indicator is another sensor currently available for use as a component of the Chronotox System. Suitable for the measurement of silica, lead fumes, pharmaceutical powders as well as many other types of particulates found in manufacturing or laboratory situations, the battery-operated P-5 uses the light scattering technique to measure dusts over a range of either 0.01-100 mg/m or 0.001-10 mg/m (Figure 6). 

At present, dry powder inhalers (DPIs) are not used as commonly in the United States as are pMDIs. DPIs have been the last pharmaceutical inhalation aerosol system developed. Although the concept of operation is readily envisioned for these devices, the development of an efficient dry powder dispersion device intended for lung delivery has been notoriously difficult. Most of these devices function by using interactive mixtures of fine drug particles (1-5 pm diameter) and carrier excipient particles (usually 75 200 pm). Some evidence suggests that DPI performance is dictated largely by the physicochemical properties of the excipients used (5). However, as will be discussed, the availability of different choices of excipients is very limited, particularly in the United States. 

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. 

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

Peart, J. Staniforth, J.N. Meakin, B.J. Electrostatic charge interactions in pharmaceutical dry powder aerosols. Inst. Phys. Conf Ser. 1995, 143 (Electrostatics 1995), 271-274. 

Pharmaceutical inhalation aerosols are widely used for treatment of diseases such as asthma and chronic bronchitis. There are three basic types of aerosol products the propellant-driven metered-dose inhalers, the dry powder inhalers, and the nebulizers. Because of the ozone-depleting and greenhouse effects of the chlorofluorocarbon (CFG) propellants, interest in the dry powder aerosols has risen in recent years. 

The physical properties of the solid state seen in crystals and powders of both drugs and pharmaceutical excipients are of interest because they can affect both the production of dosage forms and the performance of the finished product. Powders, as Pilpel reminded us, can float like a gas or flow like a liquid but when compressed can support a weight. Fine powders dispersed as suspensions in liquids are used in injections and aerosol formulations. Both liquid and dry powder aerosols are available and are discussed in Chapter 9 some properties of compacted solids are dealt with in Chapter 6. In this chapter we deal with the form and particle size of crystalline and amorphous drugs and the effect these characteristics have on drug behaviour, especially on drug dissolution and bioavailability. 

Chew NY, Chan HK. The role of particle properties in pharmaceutical powder inhalation formulations. J Aerosol Med 2002 Eall 15(3) 325-330. 

Sievers RE, Huang ETS, Villa JA, Kawamoto JK, Evans MM, Brauer PR. Low-temperature manufacturing of line pharmaceutical powders with supercritical fluid aerosolization in a bubble dryer. Pure Appl Chem 2001 73 1299-1303. 

Shekunov BY, Kippax P, Jones L, Rehman M, Y ork P. Analysis of dry powders aerosols using laser diffraction. Proceedings of the American Association of Pharmaceutical Sciences Annual Conference, Denver, AAPS Pharm Sci 2001 3 108. 

Aerosol science plays a key role in many different fields including (a) atmospheric sciences and air pollution, (b) Industrial production of pigments, fillers, and specially metal powders, (c) fabrication of optical fibers, (d) industrial hygiene, and (e) contamination control in the microelectronics and pharmaceuticals industries. Aerosols present in such applications can usually he considered as desirable or undesirable, but the same basic concepts apply to both types. Specialist. in the various applied fields increasingly make use of similar theoretical concepts and experimental techniques in solving aerosol problems. These common approaches are the focus of this book. 

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

Hickey AJ. Pharmaceutical inhalation aerosol powder dispersion an unbalancing act. Am Pharma Rev 2003 6(4) 106-110. 

Figure 6.20. The Aero-Disperser attachment for the Aerosizer , enables aerosol preparation at controlled shear rates, a) Internal structure of the AeroDisperser. b) The effect of various shear rates can be seen from the size distributions generated for a pharmaceutical powder intended for use as a therapeutic aerosol.

The inclusion of the a routine microbial limit test in a marketed product stability protocol depends on the pharmaceutical dosage form. Typically, the test would be used only for nonsterile products, especially oral liquids, nasal sprays, and topical liquids, lotions, and creams that have sufficient water activity to support the growth of microorganisms. In contrast, tablets, powder- and liquid-filled capsules, topical ointments, vaginal and rectal suppositories, nonaqueous liquids and inhalation aerosols with a water activity too low to allow for the product to support the growth of microorganisms would not be routinely tested. 

Powder injection applies many of the principles of pulmonary delivery of dry powders to the lungs The drug has to be in the form of very small particles, is dispensed from a reservoir, and is delivered as an aerosol i.e., particles are dispersed in a gas. Liquid or dissolved drug can be delivered by precipitation or adsorption onto carrier particles. The big difference with pulmonary delivery is the momentum at which the particles are delivered. Driven by a high-pressure helium gas stream, the particles travel fast enough to penetrate the outer layer of the skin, the stratum corneum. The design of devices to deliver needle-free injection of solids was pioneered by researchers at the University of Oxford who founded PowderJect Pharmaceuticals PLC in 1993 (now PowderMed Ltd.) to develop the only powder-based technology so far. Since that... 

Inhalation and direct skin contact are the most common routes of chemical exposure. The greatest exposure risk in handling potent compounds in an analytical laboratory therefore occurs when handling solid materials due to the potential to generate and inhale airborne dust particles of the compound. Once the potent material has been placed into solution, the airborne exposure risk is reduced and solutions of potent compounds may be handled in a manner similar to other nonpotent pharmaceutical compounds, assuming good laboratory practices are followed. Caution should be taken not to aerosolize the solutions since this could create an inhalation hazard. In addition, any sample solution spills should be adequately cleaned to prevent powder deposits of the compound from forming, which could potentially become airborne after the liquid has dried. 

The delivery of pharmaceutical aerosols as a dry powder is no longer perceived as the second best method to deliver drugs to the lung. This is because of the mounting technologies, which are capable of making stable powders of respirable size and devices competent to deliver accurate doses and versatile payload. 

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