Services to determine stability in the presence of water, water content of sample materials, quantity and how quickly water vapor is adsorbed and/or absorbed by a material, and dissolution in aqueous media...
Karl Fischer Titration -
Determine trace amounts of water
| Application AND Technique Description | ||
|---|---|---|
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Karl Fischer (KF) titration is a fast, accurate, and precise method for determining the water content
in liquids and solids. The water content is measured automatically using a KF titrator, and takes only
minutes to perform. The KF titration is selective for water. By contrast, the loss on drying method
requires several hours to obtain results and the weight loss observed might not be due completely to
water content. Materials that are highly hygroscopic should be prepared for testing under nitrogen.
We offer three types of KF titration methods: Coulometric titration KF - Coulometric KF titration is suitable for samples with a low water content, e.g., 1 ppm to 5%. Volumetric titration KF - Volumetric KF titration is suitable for samples with a water content in the range 100 ppm to 100 %. Coulometric/Volumetric titration KF with Drying Oven - Coulometric/volumetric KF titration with a drying oven attachment is suitable for insoluble materials, or materials that undergo side reactions using conventional KF titration reagents. |
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| Instrument Used | Model | Notes: |
| Mettler Toledo |
V20 and C20
(Coulometric, Volumetric, Oven) Low RH handling is available |
cGMP Testing is Available Wiki Reference for Karl Fischer Titration |
Dynamic Vapor Sorption -
Measure how quickly and how much a material absorbs a solvent
| Application AND Technique Description | ||
|---|---|---|
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Dynamic vapor sorption (DVS) is a gravimetric technique that measures how quickly and how much of
water or solvent is absorbed by a material. The instrument consists of a very sensitive balance that
is enclosed such that the vapor concentration can be varied around the sample on the balance pan. The
result of a DVS measurement is a plot of mass change against vapor concentration. For most
pharmaceutical applications, water is of primary interest and vapor concentration is simply relative
humidity (RH).
Kinetic DVS data show the change in sample mass at static RH as a function of time. Water uptake rates and diffusion coefficients are obtainable from such data. For pharmaceutical materials, moisture content at equilibrium is of paramount importance. Very hygroscopic substances may need to be stored under controlled RH conditions to avoid physical changes. Some crystals are variable hydrates, in which the water content in the crystal depends on the ambient RH. In order to manufacture a drug product using a crystalline API of that type, proper API loading is only possible if the water content of the API is known. That is more easily done by drying a sample on a DVS instrument rather than using Karl Fischer titration. DVS studies are not only applicable to APIs and formulated products, but to packaging materials as well. DVS is one of the most sensitive techniques for determination of the amorphous content of pure substances or mixtures. An advantage of DVS in that context is its ability to analyze a relatively large sample (milligrams) where spectroscopic techniques interrogate much less. That is particularly important when studying solid mixtures, which are notoriously inhomogeneous. DVS is useful for
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| Instrument Used | Model | Notes: |
| TA Instruments |
Multiple Q5000s
Thermal Advantage for Q series v. 5.4.0 |
Wiki Reference for Dynamic Vapor Sorption
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Low RH Analysis -
Control for humidity during testing
| Application AND Technique Description | ||
|---|---|---|
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Temperature and humidity strongly influence manufactured product performance. A Relative Humidity
percentage (%RH) is temperature specific. For example, the amount of moisture in the air at 20˚C
(68°F) and 50% RH is not the same as 10˚C (50°F) and 50% RH. As the temperature of air is reduced, its
ability to hold moisture is also reduced. Thus, for a given amount of water vapor in the air - the
lower the temperature, the higher the RH. The manufacturing industry utilizes temperature and humidity
testing to get an accurate assessment of how their products will perform in any environment. This
process serves to establish product reliability as well as ensure regulatory compliance. Temperature
is the most common product stress found in environmental fluctuations. Humidity is the second leading
environmental stressor affecting manufactured products.
Triclinic offers a variety of Low RH analysis capabilities including:
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| Instruments Used | Model | Notes: |
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Dry Box
Variable Humidity Chambers Dessication Encapsulation Sampling and Testing |
Various | Please contact us for specific needs and design of experiment |
Dissolution Testing -
Bioavailablity Assessment
| Application AND Technique Description | ||
|---|---|---|
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Used to provide critical in vitro drug release information for both quality control purposes, i.e., to
assess batch-to-batch consistency of solid oral dosage forms such as tablets, and drug development,
i.e., to predict in vivo drug release profiles.
Several dissolution apparatuses exist. In the United States Pharmacopoeia (USP) General Chapter <711> Dissolution, there are four dissolution apparatuses standardized and specified. They are: USP Dissolution Apparatus 1 - Basket (37 °C) USP Dissolution Apparatus 2 - Paddle (37°C) USP Dissolution Apparatus 3 - Reciprocating Cylinder (37 °C) USP Dissolution Apparatus 4 - Flow-Through Cell (37 °C) The vessels of the dissolution method are usually either partially immersed in a water bath solution or heated by a jacket. An apparatus is used in solution within the vessels for a predetermined amount of time which depends on the method for the particular drug. The dissolution medium within the vessels is heated to 37°C with an acceptable difference of ± 0.5°C. ample solutions collected from dissolution testing are commonly analyzed by HPLC or Ultraviolet-visible spectroscopy for particular release statistics. |
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| Instrument Brand | Model | Notes: |
| Van Kel | VF750D with UV/VIS or HPLC detection |
cGMP Testing is Available Wiki Reference for Dissolution Testing |
Disintegration Testing -
Quality control of drug product
| Application AND Technique Description | ||
|---|---|---|
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Before a tablet/hard gelatin capsule can dissolve and allow the active drug to be absorbed into the
body, it must first disintegrate into smaller particles. The current apparatus described in the
Pharmacopoeias (e.g. <USP Chapter 701>) was designed to provide a reproducible and standardized
method of ensuring that disintegration has taken place. Drug products to be tested are placed in one
of 6 vertical tubes arranged in a circular basket arrangement. The lower end of the tubes is covered
by a sieve mesh. During testing, the basket assembly is raised and lowered in simulated gastric fluid
at 37 degrees C and the tablet is continually "hammered" by a plastic disk of defined proportions to
simulate in vivo conditions. The drug product is said to pass the disintegration test if no residue
remains on the mesh after the designated test period.
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| Instrument Used | Model | Notes: |
| Testerion | DT2 | Wiki Reference for Disintegration Testing |