Characterization of on! Nicotine Pouches Part 2: Nicotine ...
Transcript of Characterization of on! Nicotine Pouches Part 2: Nicotine ...
Fadi Aldeek, Nicholas McCutcheon, Cameron Smith, Hannah
Grisevich, Christopher J. Suarez, John H. Miller, Christopher
B. McFarlane, Karl A. Wagner, and Tim L. Danielson.Altria Client Services LLC, Richmond, VA 23219
2020 CORESTA Congress Online
Sciences.altria.com
Characterization of on!® Nicotine Pouches – Part 2: Nicotine Dissolution Release Profiles
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INTRODUCTION➢ Oral tobacco products exist in two major categories; traditional smokeless tobacco and modern oral nicotine products.
▪ Evaluate product performance
▪ Guide product design
▪ Product to product performance comparison
▪ Develop in-vivo / in-vitro correlation (IVIVC)
➢ Modern oral nicotine products come in various solid forms including lozenges, gums, dissolving tablets, and nicotine
pouches.
➢ on!® is an oral tobacco-derived nicotine pouch product that does not contain cut, ground, powdered or leaf tobacco.
➢ on!® is currently available with 7 flavors (e.g., Citrus, Wintergreen, Mint, Coffee, Berry, Cinnamon, and Original) and 5
different nicotine strengths (1.5, 2, 3.5, 4, and 8 mg per pouch).
➢ Dissolution testing is a laboratory test method designed to demonstrate how efficiently an active ingredient is extracted out
of a solid oral dosage into solution:
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STUDY OVERVIEW➢ Adopted a robust nicotine release method utilizing the USP-4 flow-through cell apparatus.1
1- J. H. Miller, T. Danielson, Y. B. Pithawalla, A. P. Brown, C. Wilkinson, K. Wagner, and F. Aldeek. Development and validation of dissolution testing for nicotine release from smokeless
tobacco products using flow-through cell apparatus and UPLC-PDA. J. Chromatogr B 2020, 1141, 122012.
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➢ Evaluated the nicotine release profiles from the 35 varieties of on!® nicotine pouches (7 flavors with 5 nicotine strengths
each).
➢ Performed product-to-product comparison for the 35 varieties of on!® pouches by calculating the difference factor (f1) and
similarity factor (f2) following FDA’s Guidance for Industry.2,3
➢ Compared on!® nicotine pouches to commercially available traditional pouched smokeless tobacco products.
2- Food and Drug Administration, Center for Tobacco Products, Office of Science, Dissolution as a critical comparison of smokeless product performance: SE requirements and
recommendations for the review of dissolution studies. 2016.
3- Food and Drug Administration, Guidance for Industry: Dissolution testing of immediate release solid oral dosage forms. 1997.
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DISSOLUTION METHODOLOGY
Fractions CollectorPumpCells Holder
SOTAX CE7 Smart Flow-Through Cell Apparatus (USP-4)-UPLC-PDA
Flow-Through Cell
▪ Flow rate 4.0 mL/min ▪ Temperature 37 °C
https://www.sotax.com/en/usp4_dissolution_testing/
▪ 12 replicates ▪ 9 fractions per replicate
Dir
ecti
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of A
rtif
icia
l S
aliv
a F
low
Filter Chamber
5 mm Ruby Bead
3 mm Beads1 mm Beads
on!® Pouch
Time (min)
Inte
nsi
ty
Nicotine
UPLC-PDA*
*UPLC-PDA: Ultra-high Performance Liquide Chromatography (UPLC)-Photodiode Array (PDA)
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CUMULATIVE AND % RELEASE PROFILES
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n =12
Averaged Nicotine per Fraction (12 replicates) Sum of Averaged Fractions
Cumulative Release Profile% of Total Release Profile
Calculation of nicotine cumulative and % release profiles from 4 mg Mint on!® nicotine pouches (n=12). Error bars represent ± 1 standard deviation.
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Cu
mu
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mg/
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Time (min)
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RESULTSNicotine Cumulative Release Profiles
Similar observations were seen for Original, Citrus, Berry, Wintergreen, Coffee, and Cinnamon on!® nicotine pouches.
Cumulative release profiles of nicotine from Mint on!® nicotine pouches (n=12) across all nicotine strengths. Error bars represent ± 1 standard deviation.
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Nic
oti
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g/p
ou
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Time (min)
1.5 mg 2 mg 3.5 mg 4 mg 8 mg
Mint n = 12
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RESULTS
Similar observations were seen for Original, Citrus, Berry, Wintergreen, Coffee, and Cinnamon on!® nicotine pouches.
% of total release profiles of nicotine from Mint on!® nicotine pouches (n=12) across all nicotine strengths. Error bars represent ± 1 standard deviation.
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Time (min)
1.5 mg 2 mg 3.5 mg 4 mg 8 mg
% of Total Release Profiles of Nicotine
Mint n = 12
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RESULTS
f1 values up to 15 (0-15) and f2 values of 50 or greater (50-100) demonstrate similarity or equivalence between
two products.
➢ Determine nicotine release profiles for two products (12 replicates per product)
➢ Use mean dissolution values from both curves at each time point to calculate difference factor (f1) and similarity factor (f2)
*Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms, FDA Center for Drug Evaluation and Research (CDER),1997.
Approach based on FDA guidance from CDER*
Dissolution Profiles Comparison
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RESULTS
Mint on!®
Compared Products f1 f2 Equivalency
4 mg vs 1.5 mg 0.8 97.4 Yes
4 mg vs 2 mg 3.9 79.0 Yes
4 mg vs 3.5 mg 5.9 71.5 Yes
4 mg vs 8 mg 7.4 67.1 Yes
on!® nicotine pouches exhibit equivalent nicotine release profiles across all flavor variants and nicotine strengths.
Product to Product Comparison using f1 and f2
Similar observations were seen for Original, Citrus, Berry, Wintergreen, Coffee, and Cinnamon on!® nicotine pouches.
f1 and f2 values for compared on!® nicotine pouches across all nicotine strengths for each flavor. The on!® 4 mg pouches for each flavor were used as
the reference products for all comparisons.
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RESULTSNicotine Cumulative Release Profiles
Cumulative release profiles of nicotine from 3.5 mg Wintergreen flavored on!® nicotine pouches, Wintergreen Skoal® Bandits, and Wintergreen Skoal® pouches (n=12). Error bars represent ± 1 standard deviation.
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Nic
oti
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(m
g/p
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Time (min)
Skoal Bandits Skoal Pouches on! Pouches
n = 12
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RESULTS
% of Total Release Profiles of Nicotine
% of total release profiles of nicotine from 3.5 mg Wintergreen flavored on!® nicotine pouches, Wintergreen Skoal® Bandits, and Wintergreen Skoal® pouches (n=12). Error bars represent ± 1 standard deviation.
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Time (min)
Skoal Bandits Skoal Pouches on! Pouches
n = 12
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RESULTS
Compared Products f1 f2 Equivalency
on!® Wintergreen vs Skoal® Bandits 8.1 61.0 Yes
on!® Wintergreen vs Skoal® pouches 21.1 46.0 No
3.5 mg Wintergreen on!® was found to be equivalent to Skoal® Bandits and different from Skoal® pouches (Wintergreen flavored traditional pouched moist smokeless tobacco product).
Product to Product Comparison using f1 and f2
f1 and f2 values for compared 3.5 mg Wintergreen on!® nicotine pouches to Wintergreen flavored Skoal® Bandits and Skoal® pouches.
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SUMMARY
➢ Following FDA guidance, we applied a robust USP-4 dissolution method to determine the nicotine
release profiles for a variety of on!® nicotine pouches.
➢ Demonstrated a dose dependent response for the cumulative nicotine release profiles for all nicotine
strengths.
➢ Nicotine release rate for each flavor variant is equivalent based on % of total nicotine release profiles
and f1 and f2 criteria.
➢ The nicotine release rate for 3.5 mg Wintergreen on!® nicotine pouches was found to be equivalent to
Skoal® Bandits but faster than Skoal® pouches (Wintergreen flavored traditional pouched moist smokeless tobacco product).
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THANK YOU
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Visit our Altria Science website to access this presentation and learn more about our scientific work.
Sciences.Altria.com or scan the QR Code below.
Questions? Email us! [email protected]
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