Active Pharmaceutical Ingredients Released by Oral Medication Dispensing Robots

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Active Pharmaceutical Ingredients Released by
Oral Medication Dispensing Robots
David Alburty, Pamela Murowchick, Andrew Page

• 7C.05
• AAAR 27th Annual Conference and Exposition,
  Orlando, FL, October 22, 2008

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EPA Air Pollution Standards

• The Clean Air Act established two types of
  national air quality standards for particle
  pollution PM-10 and PM-2.5.

• Fine particle (PM-2.5) standards are based on
  their correlation with serious health problems
  ranging from increased symptoms, hospital
  admissions and emergency room visits, and
  premature death for people with heart or lung
  disease.

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Indoor Air Quality Concerns

• Intake Fraction It is generally accepted that
  the likelihood of inhalation of particles from an
  indoor source is 100 1000 times that for
  inhalation of particles from a similar source
  while outdoors.
• The effect of proximity to an indoor source is
  interesting and complicated.

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• Due to the known hazards from airborne PM, we
  studied the potential for pill dust generated
  by the agitation of pills in common dispensing
  machines found in retail pharmacies to be emitted
  as respirable dust.

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Potential Hazards of Airborne Pill Dust

• Airborne active chemical compounds found in pill
  dust have the potential to alter body functions.
• Fine fraction pill dust can be conserved and
  recirculated throughout the pharmacy through
  typical heating, ventilation and air conditioning
  systems.
• There are no defined safe levels for these types
  of particles in most cases.

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Comparison Study

• We compared PM-10 and PM-2.5 emissions from
  two leading robotic prescription dispensing
  machines, the ScriptPro SP 200 and the
  McKesson/Parata RDS. These are widely used in
  thousands of drugstores across the U.S. As a
  control, we also conducted sampling in pharmacies
  where pills are counted dispensed manually.

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Manual Pharmaceutical Dispensing

• 80 of prescriptions filled are dispensed as
  loose tablets or capsules supplied in bulk stock
  bottles.
• The pills are counted out manually into a slot on
  a filling tray using a spatula, and then poured
  from the tray to a prescription vial, according
  to the physicians directions, then labeled.
• Any excess pills are poured back into the stock
  bottle.
• Pharmacies with dispensing robots also do some
  manual counting.

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Robotic Dispensing

• Robotic dispensing machines count pills into
  vials, print and apply labels, and sort the
  prescriptions by patient name.
• They are able to fill at a much faster rate than
  manual filling and with less potential for
  errors.
• Pills are dispensed from large storage cells
  within the machine and transported into the vials
  in various ways, according to the design of the
  particular machine.

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ScriptPro SP 200

• In this machine, pills are maneuvered into
  prescription vials using a rotating platen inside
  each storage cell. They are counted by an
  optical sensor as they drop into the vial.

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Parata RDS

• This machine uses differential air pressure
  inside the dispensing cell to agitate the pills.
  
• While the pills are being agitated, compressed
  air jets force them through a nozzle and into a
  prescription vial.
• They are counted using optical sensors as they
  pass through the nozzle.

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Pill Dust on Parata RDS

• Pill dust was plainly visible on both the inside
  and outside of the Parata RDS. This was not
  observed on the ScriptPro SP 200.
• An analysis was performed to determine if the
  Parata RDS dust contained active pharmaceutical
  compounds of respirable particles.

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Collecting Pill Dust from the Parata RDS
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Parata RDS Pill Dust Analyzed

• Nine separate dust samples were collected from
  various parts of the Parata RDS and sent to
  Inovatia Laboratories for analysis using
  LC/DAD/MS.
• A limited method was developed and sample
  aliquots were analyzed.
• The results indicated 6 -16 peaks in each sample
  which included Acetaminophen, Levofloxacin,
  Mirtazapine, Methocarbamol, Carisoprodol,
  Loratadine, Diazepam and Valacyclovir, and
  unidentified compounds.

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Cleaning the Parata RDS

• Manufacturer recommended operation of the Parata
  RDS requires that dust generated during the
  dispensing process be removed from the pill count
  sensors.
• This is accomplished by using canned air
  supplied by the manufacturer.
• Instruments showed that the resulting dust cloud
  remains in the pharmacy for several minutes after
  cleaning.

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Nanoparticles in Pill Dust

• Oral pharmaceutical tablets and capsules are
  often comprised of active nanoparticles, which
  can be embedded in excipients and released in
  pill dust.

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Re-Aerosolizing the Parata RDS Pill Dust in a
Measurement Chamber

• Pill dust from the Parata RDS was re-aerosolized
  in an Aerosol Test Chamber at AlburtyLab using a
  Small Scale Powder Disperser.
• An Aerodynamic Particle Sizer (APS) and a
  Scanning Mobility Particle Sizer (SMPS) were used
  to measure the particle size distribution.

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Findings Fine Particulate Matter and Active
Pharmaceutical Compounds

• 94 of the respirable particles (by number)
  reaerosolized from dust samples removed from the
  Parata RDS were in the PM-2.5 range.
• The samples were also shown by Mass Spectrometry
  to include active pharmaceutical compounds
  (example Ibuprofen).

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Testing the Air in 15 Pharmacies

• Five Parata RDS.

• Five ScriptPro SP200.

• Five with no automated system.

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Test Methodology

• Pharmacy aerosols were observed over 24-hr
  periods.
• Emissions of pill dust from dispensing operations
  were sensed using an Aerodynamic Particle Sizer
  Spectrometer (APS).
• Air samples were collected with paired quartz
  fiber filters near dispensing areas and were
  analyzed by Inovatia Laboratories using
  HPLC/DAD/MS at MU.

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Air Sampling Parata RDS

• The APS sampling tube and reference filters were
  stationed on the edges of the dispensing area at
  approximate breathing height.

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Air Sampling - Parata RDS
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Air Sampling - ScriptPro SP 200
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Air Sampling - Manual Counting
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Data Analysis

• Dispensing data logs were merged with APS
  readings to correlate emission levels with drugs
  dispensed.
• Activity logs were also merged with APS readings
  to show other activities which could interfere
  with instrument readings such as vacuuming, heavy
  customer traffic, trash collection, ventilation,
  etc.
• Some medications were found to be dustier than
  others.

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ScriptPro SP 200
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Parata RDS
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Manual Dispensing
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PM-2.5 in 15 Pharmacies
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ScriptPro SP 200 PM-2.5
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4 More ScriptPro SP 200
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Parata RDS PM-2.5
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4 More Parata RDS
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Manual Counting PM-2.5
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4 More Non-Robotic Pharmacies
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Comparison of Results vs. EPA National Ambient
Air Quality Standards

• The data show that PM-2.5 and PM-10 emission
  peaks from Parata RDS dispensing and cleaning
  operations frequently exceed EPA NAAQ standards.
• Given that personnel in pharmacies are working
  indoors and are subject to proximity, constant
  exposure, and constrained dispersion factors,
  there may be an increased health impact risk.

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Additional Study Recommended

• Extensive studies have been performed for certain
  classes of worker such as in coal mines, cotton
  mills, etc.
• This is believed to be the first study addressing
  exposure to personnel in pharmacies arising from
  pill dust.
• Data collected during this study could be further
  analyzed to plan a health risks effects study
  from exposure to aerosolized active
  pharmaceutical compounds in the particle size
  ranges observed.

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Acknowledgment
This work was supported by ScriptPro LLC of
Mission, Kansas www.scriptpro.com
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Contact Information
David S. Alburty AlburtyLab, Inc. 128 E. Main
St., Drexel, MO 64742 www.alburtylab.com dalburty_at_
alburtylab.com