Thermal humidity

Thermal/humidity stress testing involves exposing samples to various conditions of temperature and humidity. Once the conditions are chosen, the samples are placed in either ovens which control the conditions or saturated solutions of salts in desiccators. The physical appearance of the sample is important and should be monitored throughout the study. In addition, any loss or gain of water should be noted as well. 

Minimally, one should have a brief foreknowledge of the thermal and thermal/humidity solid-state stability of the API prior to initiation of excipient compatibility studies. These protocols should include investigation of stability at various temperature and humidity conditions and should always include information about both chemical stability and physical-form integrity of the API. Thermal and thermal moisture-induced solid-state chemical reactions are well known (5), with hydrolysis and oxidation being the most prevalent mechanisms of decay. Changes in physical form with thermal and... 

Kinetic information on the chemical changes of excipient compatibility samples is a direct outcome of most formulation compatibility studies. Because accelerated conditions of thermal and thermal humidity stress are employed, degradation will often occur at these conditions. A brief kinetic evaluation of the data can address the behavior and extent of decay such that degradation data can effectively be utilized to determine levels and conditions of compatibility (96). It is not the aim of this section to recommend full kinetic treatment of decay rather it is to describe simple concepts and exercises that will help the excipient compatibility formulator utilize their data most effectively. Several experimental factors can be included in the initial experimental design of excipient compatibility studies to make kinetic analysis more powerful, and even with small studies having a limited amount of samples for analysis, a brief kinetic treatment of the data is recommended. 

The temperature and moisture content generate the volumetric thermal-humid strain, which is expressed as... 

Acid, base, light, oxidative, thermal, thermal humidity... 

In case study A.ll, a degradant was observed in drug product-forced degradation (thermal/humidity) studies of the drug substance salt. This compound was at a later stage of development and proactive efforts were... 

According to the thermal/humidity stress testing conditions selected, samples are placed into appropriate ovens. If humidity ovens capable of 70°C/30% RH and 70°C/75% RH are not available, saturated salt solutions contained in desiccators can be used to control humidity accurately. These conditions are particularly useful for high-potency drug substance compounds for which samples must be contained. A saturated NaCl solution is used to obtain conditions of 75% RH at 70 °C and a saturated MgCl2 solution is used to obtain conditions of 30% RH at 70 °C. 

TABLE 3 Guidance for Thermal/Humidity Experimental Setup... 

The laboratory accelerated corrosion test practiced at Cortec Co. includes exposure of cold-rolled steel plates wrapped in packets of inhibited films and subjected to thermal-humid atmosphere in special cabinets at 54° C temperature and 95% humidity for 21 days (504 h). Upon the termination of the test the corrosion damage of the samples is estimated. 

Even though wet spinning may cause water pollution, it has so far been widely used for the production of synthesis fibers. Thus, the properties of T -SMPU as well as the effects of thermal-humidity conditions on the stractuie, the thermal-mechanical properties and shape memory properties of wet-spun SMPU fibers have been closely studied. Since the concentration of anorganic solvent in the water bath may influence both the recycling process of waste water, and the behavior and properties of wet-spun SMPU fibers, its effects on SMPU fibers will also be described. 

The PB A-based, wet-spun SMPU fibers were fixed onto paper cones and placed in a humidity cabinet at various temperatures and humidity conditions. The samples were stored in a specifically conditioned room (21°C, 65RH%) for at least one week before examination. The effects of the thermal-humidity conditionings on the thermal, mechanical and shape memory properties of the wet-spun fibers were then examined. Table 11.5 shows the conditions and coding of the temperature-humidity conditioning. 

Table 11.5 Codes and conditions of thermal-humidity treatments on SMPU fibers...

The initial modulus of the specimens was also examined. The mean values of the initial modulus, calculated with a slope at 10% strain in the stress-strain curves, are shown in Table 11.7. The initial modirU of all specimerts after a thermal-humidity treatment were lower than those of the untreated specimens, with this becoming even more noticeable when the treatment temperature was... 

Tables 11.8 and 11.9 show the statistics of the breaking strain and tenacity of thermal-humidity treated PBA-based SMPU fibers, when compared with an untreated specimen. Condition e has a temperature of 50°C and relative humidity of 30%. When condition e occurs, the breaking tenacity drops fi om 0.532 to 0.477 cN/dtex, and then increases with treatment time. Finally, the breaking tenacity of specimen e-190 returns to the original value of 0.52cN/dtex. However, the differences in the...

When humidity conditions increase from 30 to 80%, the situation becomes more complex. A general trend cannot be obtained in the relationship between the breaking properties and treatment time. In combination withthe above observations for the SMPU libers treated at 50°C, it is suggested that there has to be some other time-dependent reaction, which resulted in the opposite effects of plasticizatioa The data obtained above is the final result of the competition between different reaction mechanisms in the thermal-humidity treatments. 

Table 11.14 Shape fixity and shape recovery ratio of PBA-based SMPU fibers after thermal-humidity treatment for 100 and 190 hours...

The effects of thermal-humidity conditioning on the chemical stracture of PBA-based SMPU fibers were measured by an FT-IR and the results are shown in Figs 11.18 and 11.19. The scanning range was 450 to 4000cm and, on average, 16 scans were taken for each specimen. 

Also studied were PB A- and PCL-based SMPU fibers, spun by the wet-spinning process. The effects and mechanisms of thermal-humidity treatments on the shape memory properties of PBA-based SMPU fibers were examined based on mechanical, thermal and chemical analyses. The ejqrerimental results show that PBA-based SMPU fibers are not as sensitive to water as PCL-based fibers. The reduction of shape memory properties after high-temperature conditioning is... 

TABLE 7 Thermal/Humidity Best Practice Conditions... 

DP degradation cannot be predicted solely from the stability studies of the API in the solid state or solution. The non-APIs can also react with the API or catalyze degradation reactions. Impurities in the excipients can also lead to degradation in the DP not originally observed in the API. For solid oral DP formulations, heat, light, and humidity are often used as appropriate stress conditions. As indicated for API, DP stress conditions should result in approximately 5-20% degradation of the API or represent a reasonable maximum condition for a given formulation. The specific conditions used will depend on the chemical characteristics of the DP. For a solid DP, key experiments are thermal, humidity, and photostability. For solution formulations, additional experiments recommended in addition to thermal and photostability include acid/base hydrolysis and oxidation. 

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