Moisture is a crucial parameter in the manufacture of bulk solid pharmaceuticals. The producing method of pricey medicine is usually sophisticated, and through a method that has crucial stages that occur over many days, quick and correct determination of moisture content is important.
Generally, moisture analysis needs to be performed in product and process development, as well as during manufacturing to specify and control the maximum allowable moisture content at each step. Knowing the moisture content at each step is part of the very careful process control required during manufacture.
Several drying ways are utilized for moisture analyses, including mathematical determination established on infrared detection and chemical titration. The Karl Fischer technique involves adding a reagent to the sample that reacts with the water present to manufacture a non-conductive chemical. However, this solely provides a reliable measure of moisture content if most of the moisture is due to water. A sample containing very little water, however high levels of alternative volatiles, can give a low moisture reading in a Karl Fischer titration, once in reality it still contains a major quantity of moisture.
There is a large list of properties of pharmaceutical product that are influenced by moisture content, and directly have an effect on how tablets are manufactured. This contains chemical stability, crystal structure, compaction, powder flow, lubricity, dissolution rate, and polymer film permeability.
The presence of moisture affects the consistency and stability of tablets. an excessive amount of moisture can cause an agglomeration of powder particles and a poor crumbly tablet; insufficient moisture can cause the tablet to fall apart. Fine-grained excipients might fail to flow if they’re too wet, and a few active pharmaceutical ingredients (APIs) would possibly crystallize or change shape if there’s an excessive amount of moisture. Solid dosage forms are created utilizing a vast range of processes as well as freeze drying, fluid bed drying, compaction, granulation, and extrusion. All of those operations rely on the quantity and the state of water present. Moisture can even influence the chemical/physical properties of individual active ingredients and excipients.
That is why it’s essential to analyze moisture content throughout manufacture and understand how moisture content affects every individual step throughout method development in order to establish specifications and parameter limits.
The thermo gravimetric technique of moisture analysis is usually accepted as the most reliable. though numerous means of heating the sample have been utilized to try and improve accuracy, infrared radiation remains one among the most popular drying techniques.
On exposure of the sample to infrared radiation, the surface of the sample is heated 1st. The energy is then conducted from the surface through the complete volume of the sample. this point for the heat to conduct throughout the whole sample has been the limiting factor of standard infrared loss-on-drying moisture analyzers. If the sample has high dielectric properties, the drying time can increase. This result is compounded by the partial reflection of the infrared energy, preventing efficient heat transfer.
Since effective moisture determination depends on the speed at which measurements are obtained, this absorption delay makes it impossible to see the moisture content of high-moisture samples utilizing standard infrared loss-on-drying analyzers during a production atmosphere.
In addition, it’s impossible to make sure that the heat has effectively permeated through the whole sample since the temperature measuring is created in the cavity instead of rather than sample itself. This carries the chance that moisture remains in the middle of the sample, giving an underestimation of the moisture content. Conversely, the surface of the sample continues to be heated for the whole time required for the heat to be absorbed throughout the sample that might lead to scorching of those areas.
Furthermore, the analyzers can’t be used directly on the manufacturing line, because of the need for a fume hood to get rid of the water vapor and different volatiles. This necessitates a delay whereas samples are transported to the analyser, therefore any production parameters that need real-time feedback won’t be optimally controlled, probably impacting product quality and variability.
Heating utilizing halogen components has been adopted in preference to standard infrared loss-on-drying moisture analyzers since the best heating temperature may be achieved more quickly. Halogen drying, however, still carries the danger of uneven heat exposure which may undermine the results obtained.
For manufacturers, it’s essential to think about the impact of moisture in bulk materials additionally because the finished product. Moisture content fluctuates from batch-to-batch, and to attain consistency in formulation there should be a reliable technique to see moisture content accurately. To be effective, moisture determination strategies should be quick, repeatable, and precise.
We at KERONE have a team of experts to help you with your need for moisture analysis in various products range from our wide experience.