Originally Published PMPN January 2005
Drug Delivery
New Drug-Delivery Option Improves Quality of Life
Breakthroughs in pulmonary and upper respiratory drug delivery show great promise for creating more-effective delivery devices.
by Rodney E. Thompson
Vapore Inc.
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| The Capillary Force Vaporizer (CFV) generates a powerful jet of vapor from unpressurized liquid, with no moving parts. |
Because MDIs account for 70% of all inhalation therapy and are critical for treatment of asthma and chronic obstructive pulmonary disease (COPD), researchers are on the lookout for alternative delivery methods. One such innovative technology is the Capillary Force Vaporizer (CFV), which shows great promise for treatment of respiratory conditions and pulmonary drug delivery.
The pill-sized CFV generates a powerful jet of vapor from unpressurized liquid—with no moving parts. The CFV combines two natural phenomena—capillary force and phase transition—in a surprisingly potent device that is easily powered by a battery. The CFV’s portability and precise control of vapor delivery have interested pulmonary drug-delivery experts.
How the CFV Works
The CFV has a layered porous construction with a peripheral seal and an orifice plate on top. Liquid wicks into the bottom and spreads throughout the device by capillary means. Heat applied to the top surface results in vaporization in the uppermost layer. As the fluid expands from liquid to vapor, pressure builds. Because of the layered porous construction, the pressurized vapor cannot escape through the bottom. It exits through the orifice at the top of the device with surprising force.
The vaporizing material is only briefly exposed to elevated temperatures, minimizing the opportunity for thermal decomposition. Regulating power (heat) delivered to the CFV can precisely control vaporization rates. Significant quantities of material can be vaporized quickly, allowing for briefer dosing periods.
Most pure liquid compounds and solutions are good candidates for delivery using CFV technology. The chemical form of an active drug, the solvent, the rates of both heat input and liquid flow to the vaporization surface can all be adjusted to optimize delivery. Condensation of the vapor stream can be manipulated by a variety of means to achieve the desired micron-sized droplet for delivery into the lungs. The CFV can vaporize many active drug formulations, including prescription drugs, OTC medications, and self-care products.
Packaging Options
CFV devices are small. One suitable for pulmonary drug delivery would be the size of a breath mint, powered by a small battery. Many packaging options are possible for active drug compounds, and the optimum approach may vary with the drug and prescribed dose regimen. The porous member itself may be preloaded with a single dose of an active compound and used in a disposable manner, with individual doses presented in a sterile blister pack. Alternatively, a full course of multiple doses could be delivered in a single disposable ampule, with dosing regulated by a simple electronic circuit controlling power to the heat-activated device. Refillable reservoirs for longer-term therapeutic treatment are also feasible.
Aerosols for Pulmonary Delivery
Aerosols offer the potential for high rates of absorption through the lungs, creating desired plasma drug concentrations much more rapidly than oral or subcutaneous injection routes of administration. The aerosol particle size should be in the 1–3 µm range, the optimal size for inhalation directly into the deep lungs.
CFV drug delivery is limited to liquid drugs, active liquid precursors, and drug substances mixed with solvents to create suitable drug-solvent solutions. Inside the CFV, a thin liquid film is rapidly heated, vaporizing the active drug with minimal thermal decomposition. After vaporization, substances typically condense under ambient conditions to form very small aerosol particles. CFV technology enables the developer to adjust system parameters to optimize the condensing aerosol particle size and flow rate.
Pharmacology
Pulmonary drug delivery provides a noninvasive alternative to injection. The pulmonary delivery route also offers opportunities for improved and innovative drug delivery and greater patient compliance. Whenever vaporized drug substances or aerosol particles are inhaled into the deep lung, the result is a fast-onset therapeutic response, either to treat lung diseases topically or to transport molecules through the lung and into the bloodstream. The CFV operating parameters can be adjusted to maximize adsorption via the lung through the generation of an aerosol particle-sized distribution that maximizes alveolar drug adsorption.
Useful for Numerous Active Drug Compounds
CFV drug delivery aims to accelerate the onset of therapeutic response and increase plasma drug concentrations. Capillary vaporization technology is likely broadly applicable to small-molecule therapeutics, namely those with a molecular weight of less than approximately 500 g/mol. Non- water-soluble drugs can be vaporized and condensed into micron-sized aerosols as readily as water-soluble compounds.
The CFV makes rapid, reliable delivery of both water-soluble and non-water-soluble compounds possible. In some cases, drug compounds that are formulated to be solids for oral delivery have liquid (presalt) precursors that may be well suited for dosing using CFV technology. Compounds that appear well suited for dispensing via CFV technology include:
• Nicotine for use in inhaled smoking- cessation programs that seek to mimic the profile of cigarette nicotine dosing.
• Antihistamines inhaled to achieve more-rapid relief than is possible with oral dosing. With a wide range of solubility in various solvents, antihistamines should prove vaporizable under the proper conditions.
• Triptan antimigraine agents inhaled to reduce pain quickly. These agents are highly water-soluble and some are already formulated as nasal sprays.
• Erectile dysfunction agents inhaled to achieve quick response. With the exception of Viagra, the rest of these agents are mostly in the appropriate molecular-weight range for vaporization without thermal degradation.
Additional examples of the numerous classes of compounds that show promise for use with CFV technology include analgesics, steroids, opioid agonists and antagonists, antiemetics, hypnotics, decongestants, and antidepressants, to name a few.
Screening Drug
Candidates
The CFV creates very rapid vaporization of a drug in the liquid phase by combining capillary force and heat, thereby minimizing thermal degradation of the active drug compound. The first step in establishing basic feasibility is testing of the candidate compound through a standardized screening protocol. Such evaluations yield information on the stability, aerosol properties, and potential dosing profile of the compound of interest.
Prior to the physical screening process, a candidate compound should meet the following paper screening
criteria:
• Is the active drug a liquid? If not, can it be dissolved in a suitable solvent resulting in the necessary capillary and vaporization properties?
• Will the drug-containing liquid heat up quickly enough to avoid thermal degradation of the drug substance?
• Can the CFV process parameters be adjusted to condense a drug-containing aerosol in the 1–3 µm range preferred for deep lung delivery?
• If a nonaqueous liquid solvent is used, can excess residual solvent be kept out of the lungs?
While there are many variables to define, the potential benefits of CFV technology for drug delivery are significant.
Rodney E. Thompson, PhD, is a biopharmaceutical process development and product commercialization expert with 18 years of experience in the pharmaceutical industry. He may be reached at 510/985-0336, or by e-mail at rethompson@jps.net.
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