Thursday, January 6, 2011

Moisture Analysis in the Pharmaceutical Industry

When people aren’t feeling their best they often turn to medicine for relief from the symptoms that are associated with being ill. The public trusts that the products developed by pharmaceutical companies will not only make them feel better but will also not have harmful side effects. The pharmaceutical industry has earned this trust through constant research and evaluation, and adhering to strict safety guidelines designed to ensure they are bringing a quality product to market. Failing to follow these procedures could not only damage the relationship between manufacturers and customers, but also result in serious harm or even death.

One of the concerns that manufactures must manage is moisture content in its products. Pills are the products that are most thought of when people think about what the pharmaceutical industry provides. Pills need to remain whole from the time they are made to the time the purchaser ingests them. They also need to dissolve in water since this the most common transport system used by the body. Ensuring that pills are able to maintain their physical and chemical integrity requires a very specific amount of water, and accurately determining the amount of water requires precision instrumentation. Historically these measurements have been made using Karl Fischer Titration instruments, but this method has become increasingly more costly, wasteful and environmentally unfriendly.

Over the past 25 years considerable efforts have been made to develop a low cost, environmentally friendly, moisture specific method of material analysis. Leading these endeavors is Arizona Instrument LLC, who has successfully designed the Computrac® Vapor Pro® series of moisture analyzers. These instruments use RH sensor technology to accurately measure the amount of water in a material. The Vapor Pro instruments are sturdy enough for manufacturing plant floors, reduce hazardous chemical consumption making them an environmentally friendly alternative, and are capable of measuring moisture levels as low as 100ppm.

Karl Fischer Titration
First published in 1935, The Karl Fischer Titration Method has historically been the leading analytical method for detecting trace amounts of water in a variety of materials. The titration relies on the chemical reaction between I2 and H2O and has 2 methods of measuring water content.

Coulometric Titration
A Coulometric Titrator consists of an outer titration cell that contains the anode solution, a Pt detection electrode, a Pt anode and a cathode compartment that is separated by an ion permeable membrane. As water is introduced a chemical reaction is facilitated with a net oxidation reaction between SO2¬ and I2. One mole of water consumes 1 mole of I2, which generates 2 moles of electrons . The detection electrode will continue to measure a change in the electric potential until all of the I- is quenched and an excess of I2 is left in the solution. The reaction is given by the equation:
B•I2 + B•SO2 + B + H2O → 2BH+I− + BSO3
In this equation ROH is an alcohol (typically methanol) and B is a base.

Volumetric Titration
The Volumetric Titration uses the same chemical reaction as the coulometric method, however the setup is slightly different. The volumetric titrator has a cell that contains an Alcohol solution (usually methanol) and a detection electrode. An unknown amount of water is introduced to the cell and a known amount of solution containing I2, SO2 and a base are titrated into the cell until the reaction is complete.

The Karl Fischer titration method is water selective, uses small sample sizes, can analyze materials in all phases and can accurately measure water concentrations as low as 1ppm. However, there are significant drawbacks to this method as well. To facilitate this reaction requires expensive glassware that is easily broken in a manufacturing environment. Additionally, environmentally hazardous chemicals are used, which are expensive and have to be managed as hazardous waste. Also, chemicals containing mercaptans and thiol groups are known to interfere with the reaction and provide erroneous results.

Relative Humidity Sensor Technology
Relative Humidity (RH) was first used as a method of moisture determination in 1997 with the introduction of the Computrac® 3000 Moisture Analyzer by Arizona Instrument LLC. This method uses a thermoset polymer capacitor that has a selective response when in the presence of water, the same way that many RH sensors work in traditional settings such as houses, laboratory controlled environments, and dry boxes. A material is sealed in a sample vial, and then transported into an oven with inert gas blown through it. As the material gets hot, water molecules evolve off and are carried to the sensor via the carrier gas. The sensor is exposed to the water molecules and a measurable change in the electronic activity takes place. In addition, no solvent and no material processing for lyophilized pharmaceuticals are necessary for analysis. Since 1997 Arizona Instrument LLC has further developed this method of analysis and designed an instrument designed to meet the needs of the pharmaceutical industry. The Computrac® Vapor Pro® Rx is capable of testing a variety of samples using different size vials with a current sensitivity able to accurately and reliably detect moisture as low as 100ppm.

RH Sensor detection is a viable alternative to Karl Fischer Titration and can be used to determine moisture content for various products brought to market by the pharmaceutical industry. Testing has shown the Vapor Pro® 3500L can accurately determine water concentration with the same level of precision as the Karl Fischer titrator. It has shown significant improvement in ease of use when compared to single sample testing methods common to Karl Fischer analysis. Also, the Vapor Pro® has addressed durability problems associated with Karl Fischer instrumentation, which allows for testing in a wider array of locations. Further, no hazardous chemical solvents are required for sample testing, which makes the Vapor Pro a green alternative to Karl Fischer titration.

James Moore, Chemist
Arizona Instrument LLC

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