Abstract
Smoking involves heating a drug to form a mixture of drug vapor and gaseous degradation products. These gases subsequently cool and condense into aerosol particles that are inhaled. Here, we demonstrate rapid and reliable systemic delivery of pure pharmaceutical compounds without degradation products through a related process that also involves inhalation of thermally generated aerosol. Drug is coated as a thin film on a metallic substrate and vaporized by heating the metal. The thin nature of the drug coating minimizes the length of time during which the drug is exposed to elevated temperatures, thereby preventing its thermal decomposition. The vaporized, gas-phase drug rapidly condenses and coagulates into micrometer-sized aerosol particles. For the commonly prescribed antimigraine drug rizatriptan, inhalation of these particles results in nearly instantaneous systemic drug action.
Footnotes
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↵1 The term vapor refers to the gaseous state of a substance that exists primarily as a solid or liquid at room temperature and pressure. Thus, for drugs other than inhalational anesthetics, gas and vapor have identical meaning and are used interchangeably.
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↵2 Equation 3 assumes a monodisperse aerosol, i.e., all particles having equivalent size. In a real (polydisperse) aerosol, the calculated mass median particle diameter is larger by a factor of exp(3/2(ln σ)2) where σ, the geometric standard deviation of the aerosol diameter, is a unitless parameter reflecting the spread of particle sizes in the aerosol. Given a typical value for σ of 2, the resulting mass median particle diameter is approximately twice as large for a real aerosol as for a monodisperse aerosol.
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A portion of this work was supported by National Institutes of Health through the Small Business Innovation Research grant program.
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DOI: 10.1124/jpet.103.062893.
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ABBREVIATION: HPLC, high-performance liquid chromatography.
- Received November 11, 2003.
- Accepted January 29, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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