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Better Proximate Testing of Pharmaceuticals ap0232v1

Better Proximate Testing of Pharmaceuticals

Introduction
Pharmaceutical corporations are tasked with testing their products temperature uniformity throughout the cavity. Because the heating
extensively prior to distribution. Testing is performed on raw element is in the side of the furnace walls, it will not damage
materials, excipients, and during the quality control process for metallic crucibles, which can be used in the Phoenix BLACK. The
the finished product. Traditional techniques require significant user Phoenix BLACK is compatible with all crucible types, including
interaction and are subject to error. The Phoenix BLACK™ sulfated quartz, platinum, and ceramic.
ashing furnace and SMART Q™ rapid moisture analyzer provide
safe, automated, and reliable alternatives and meets all muffle All temperature measurements are performed using NIST-traceable
furnace and Loss on Drying (LOD) requirements for most global thermocouples. The exterior of the furnace is cool enough to touch,
pharmacopoeias, including those for the United States, Britain, even when the inside is at temperature. In order to access the
Japan, and Europe. Traditional techniques require hours in a drying interior of the furnace, the furnace door is placed in a holder that
oven for moisture, or Bunsen burners, heat lamps, hot plates, and prevents the user from being exposed to the hot door surface. An
muffle furnaces continuously maintained at high temperature. This optical sensor monitors the presence of the interior furnace door
equipment poses significant time loss for batch releases, as well and will activate safety locks to ensure the cavity door is held open
as safety risks, as users are directly exposed to hot surfaces and until the furnace door is put back in place. Upon method completion,
open flames. The risk of experimental error is also high, as weight active ventilation rapidly cools the furnace.
must be taken, transferred manually, and calculated. Other rapid
All sulfated ashing steps can be performed in the Phoenix BLACK
LOD and furnace systems exist, but analysis time, temperature
with the sulfated ashing option, eliminating the need for additional
uniformity, temperature measurement, and safety standards are
equipment and minimizing operator input. Acid can be added to the
all inferior to the instruments discussed herein. The SMART Q
sample in the crucible and placed directly into the Phoenix BLACK.
and Phoenix BLACK minimize risk and maximize lab efficiency by
improving the LOD and sulfated ash procedures. A lower temperature sulfating/ashing step with active vapor
scrubbing is automatically completed, prior to the high-temperature
Safer and More Efficient Sulfated dry ashing of the organic sample.
Ashing The system can be programmed with a pause step to allow the
The Phoenix BLACK is a muffle furnace that meets all microwave sulfated crucible to be removed and weighed, prior to the dry ashing
and standard muffle furnace requirements listed in ASTM, USP step. The Phoenix BLACK sulfated ashing option neutralizes toxic
(<281> ROI & <733> LOI), AOAC, FDA, ISO, DIN, ASTM D5630- acid vapor through a series of scrubbers for a more environmentally
94, and ASTM D1506-94b. The system is easily programmable, sound, laboratory-friendly solution with no emission of hazardous
contains a library of preprogrammed methods, and can ash up fumes. The system also helps the laboratory comply with ISO
to 15 samples at a time. The continuous silicon-carbide heating 14000 Environmental Management requirements to eliminate
element is encased in a quartz-fiber furnace, which maintains greenhouse gases.
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Better Proximate Testing of Pharmaceuticals ap0232v1

The Phoenix BLACK workstation allows quantification for document The Phoenix BLACK results closely match the results of the
control and automatically determines the % ROI, % LOI or % Ash. conventional muffle furnace. All of the tests were complete in
Once generated, sample information cannot be modified, aiding in significantly less time than the traditional muffle furnace. It should
21 CFR Part 11 compliance. All weighing and method information be noted that the time for the conventional muffle furnace does
is included in the data file, as well as the final result, user-entered not include additional operator actions, such as using a hot plate
sample ID, and a date/time stamp indicating when the sample or Bunsen burner, which may require an additional 30 minutes
was ashed. All methods are stored automatically and the system of operator time, prior to insertion of the sample into the muffle
provides the security of a password lock to reduce the possibility of furnace. In most laboratories, this step requires constant attention,
erroneous method modification. Data is easily exported to a LIMS as the technician cannot leave an open flame. The Phoenix BLACK
system for even easier data management. sulfated ashing option automates the sulfating/ashing step
with sulfuric acid, reducing the amount of operator attention and
Faster Loss on Drying for all creating a safer laboratory environment.

Pharmaceutical Products To evaluate the performance of the SMART Q, five healthcare

samples were obtained: Acetaminophen, Gelatin supplement, Vitamin
Healthcare products come in many forms and are made by a wide
C, Vapor Rub, and a nutritional shake. For moisture determination,
variety of processes. However, the one parameter that nearly all
a 5 g sample of each product was analyzed in the SMART Q using
products share is the need for precise control of moisture content.
a constant-weight end parameter. Testing took approximately five
Pills with too much moisture will agglomerate, while those with
minutes for all samples. Reference testing was performed in an
too little moisture may fail to hold their form. Water-based liquid
air oven in triplicate to establish a basis of comparison. The oven
products experience changes in consistency and dosage when
method was set for eight hours at 100 °C, followed by a cooling
moisture content fluctuates batch-to-batch.
period under desiccation, to ensure complete drying.
Moisture analysis in the pharmaceutical industry is widely
Results for percent moisture using the SMART Q compared closely
accomplished using infrared gravimetric moisture balances.
to air oven results, as illustrated in Table 2 (page 3). The average
Traditional infrared moisture balances are a relatively rapid
absolute difference between the SMART Q results and air oven
approach to verifying moisture content, but can take 20 minutes or
results are less than 0.003%. Table 3 (page 3) highlights the
more to complete. Furthermore, traditional moisture balances only
precision of the SMART Q. The SMART Q outperformed the air
measure the temperature of the drying cavity, not of the sample
oven reference method, exhibiting average standard deviations
itself. The inability to directly measure sample temperature can
of 0.011% and 0.013% respectively. The average dry time for the
easily result in scorched samples and inaccurate results.
SMART Q was approximately five minutes with no cavity pre-heat, a
The SMART Q™ infrared moisture analyzer is uniquely designed to necessary feature common among other leading brands of infrared
accurately and rapidly measure moisture content in a wide variety moisture analyzers.
of healthcare products. By combining active cavity ventilation and
patented quartz-halogen drying technology with direct sample Conclusion
temperature feedback, the SMART Q analyzes samples up to three
Based on the benefits provided by CEM instruments and confirmed
times faster than traditional infrared moisture balances with no
by industry leaders in the pharmaceutical manufacturing industry
risk of burning. With a highly accurate 4-place analytical balance
already using the systems, the SMART Q and Phoenix BLACK can
and 3-digit moisture readout, the SMART Q provides reliable,
provide significant increases in laboratory efficiency and speed
repeatable results in approximately five minutes. For even faster
of batch release and product validation for a range of liquid
test times, the SMART Q can be upgraded to the SMART 6, which
and powder pharmaceutical products. Both systems meet the
combines microwave and infrared technology for the fastest direct
necessary USP, ASTM, and other analytical method requirements
moisture analysis on the market.
currently in place for this industry, and do so in a way that is faster,
safer, and simpler compared to traditional techniques and other
Studies into the Time and Data of rapid alternatives. This allows production and lab managers to
Pharmaceutical Analysis have confidence in their data and confidence in the products they
make, without having to make massive production investments.
The Phoenix BLACK complies with all requirements included in
both USP <733> and <281>. To demonstrate the accuracy and
precision of the Phoenix BLACK, several different pharmaceutical
compounds were ashed for trace metal analysis. The comparison
of time and ROI for sulfated ash analysis results are shown in
Table 1 (on page 3).

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Better Proximate Testing of Pharmaceuticals ap0232v1

Table 1. Comparison of Time and ROI for Sulfated Ash Analysis

Conventional Muffle Furnace Phoenix BLACK with Sulfated Ashing Option

Sample
Temperature (°C) Time (Min) ROI (%) Temperature (°C) Time (Min) ROI (%)
Mycostatin 800 60 3.5 800 40 3.09
Amoxicillin Trihydrate (Antibacterial) 800 540 0.1-0.2 800 30 0.12
Nicotinamide (Feed Grade) 800 60 1.10 800 10 1.08
Dextromethorphan 800 60 <0.1 800 30 0.04

Table 2. Accuracy of SMART Q Compared to Traditional Oven Drying

Percent Moisture
Sample SMART Q Air Oven Difference
Acetaminophen 1.364 1.359 0.005
Gelatin Supplement 10.276 10.275 0.001
Vitamin C 0.557 0.550 0.007
Vapor Rub 11.621 11.623 -0.002
Nutritional Shake 31.265 31.265 0.000

Table 3. Precision of SMART Q for Moisture Determination of Pharmaceutical Products

Percent Moisture Replicates

Sample 1 2 3 4 5 Average STDEV
Acetaminophen 1.351 1.345 1.361 1.369 1.351 1.360 0.010
Gelatin Supplement 10.297 10.253 10.277 10.293 10.262 10.276 0.019
Vitamin C 0.551 0.555 0.560 0.545 0.573 0.557 0.011
Vapor Rub 11.582 11.642 11.636 11.645 11.599 11.621 0.028
Nutritional Shake 31.261 31.260 31.266 31.265 31.273 31.265 0.005

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