| CONDUCTIVITY µS/cm |
RESISTIVITY Ω-cm |
DISSOLVED SOLIDS ppm |
GRAINS Gpg |
| 0.056 | 18,300,000 | 0.0277 | 0.00164 |
| 0.063 | 16,000,000 | 0.0313 | 0.00181 |
| 0.072 | 14,000,000 | 0.0357 | 0.00211 |
| 0.084 | 12,000,000 | 0.0417 | 0.00240 |
| 0.1 | 10,000,000 | 0.05 | 0.00292 |
| 0.5 | 2,000,000 | 0.25 | 0.0146 |
| 1 | 1,000,000 | 0.5 | 0.0292 |
| 2 | 500,000 | 1.00 | 0.0585 |
| 5 | 200,000 | 2.5 | 0.146 |
| 10 | 100,000 | 5 | 0.292 |
| 20 | 50,000 | 10.0 | 0.585 |
| 50 | 20,000 | 25.0 | 1.46 |
| 100 | 10,000 | 50.0 | 2.92 |
| 200 | 5,000 | 100 | 5.85 |
| 500 | 2,000 | 250 | 14.6 |
| 1000 | 1,000 | 500 | 29.2 |
| 2000 | 500 | 1000 | 58.5 |
| 5000 | 200 | 2500 | 146 |
| 10000 | 100 | 5000 | 292 |
| 20000 | 50 | 8000 | 467 |
The chart above is for water at 25degree C
Ppm (parts per million) & gpg (grains per gallon) is expressed as CaCO3.
Tap water & deionized water falling outside the above range is not recommended.
YES, MACK chambers are designed specifically to meet WHO & ICH guidelines for general stability testing of new drug substances & products Q1A ® long term & accelerated refrigerator testing & photostability testing.
MACK recommends the humidity water pressure be in the range of from 10 to 20 PSI. Reach in chambers from 100 liters to 1000 liters will use from between 0.25 GPH to 3GPH. Walk-in-chambers may require considerably more, depending on size. Many factors determine the volume of water used. The most critical is the frequency & duration of the chamber door openings, whether or not ports are sealed properly & whether low or high humidity operation.
This isn’t always the easiest thing to do. Knowing the two major causes & eliminating them will go a long way to minimizing, if not altogether doing away with condensation. Air contracts as it cools. This phenomenon, in a chamber that is pulling down, actually causes outside lab air to be “sucked” into the chamber workspace. The moisture in the air will eventually freeze onto the cooling coil. It may very well end up as condensation dripping onto your product when heating up. This is more prevalent in the AGREE style chambers with overhead conditioning plenums & other rapid change rate chambers. Make sure the door gasket & all-access ports are properly sealed.
Gaseous nitrogen (GN2) & dry air purge can be used to minimize, if not totally eliminate, condensation occurrence. Purging the chamber with either of the two replaces the moisture-laden air with dry air. On a pull down the slight positive pressure prevents lab air from being sucked into the chamber workspace. With humidity chambers, perhaps the biggest contributing factor to condensation on walls & products is enabling humidity before the walls & product stabilize, or reach equilibrium with the air temperature. Since moisture is attracted to the coldest areas of the chamber (typically the walls & product), you’ll end up with condensation on the walls & possibly your product. The key is to bring up the air temperature first, let the walls & product stabilize, then enable humidity. In most cases you can run a characterization test or two first, to determine how long it takes the largest mass (be it product or wall) to stabilize
Demineralized or single distilled water with resistance measurement between 50,000 & 100,000 Ohms/cm (20 to 10 micro Siemens/cm )must be used. Do not use double or triple distilled water. Pure water above 1.0 Megohm/cm attacks metals in the humidity system & drastically reduces the life of the humidity system. It may also cause the etching of chamber windows. Untreated tap water should always be fed through a deminerlizer or deionizer cartridge before being used by the chambers humidity system. If a deminerlizer cartridge has to be downstream of the pump. Gravity alone can provide enough pressure to push a sufficient quantity of water for the vapor generator through the cartridge.
REMEMBER:-
- Do not use double or triple distilled water.
- Do not supply Deminerlized, Deionized, Double, or Triple distilled water through a deminerlizer/ deionizer cartridge.
The chamber requires 115V, 60Hz, 20A service. The power cord is equipped with a grounded plug to minimize the possibility of electrical shock from the chamber.
The 6030 requires 115V, 60Hz, 25A service. The power cord is equipped with a grounded plug Amp Twist Lock plug to minimize the possibility of electrical shock from the chamber.
The bi-modal humidification system allows for independent humidification & dehumidification. The humidity injection system utilizes atomizers to inject moisture into the chamber to achieve humidity levels from 20% to 98% RH. Dehumidification is accomplished by a refrigeration coil.
Lower humidity levels are attainable with the use of the dryer package option designed to extend the operational limits of the chamber to its minimum humidity control point of 2%RH. The dryer package uses 90 to 100 PSIG compressed air to operate.
Option 2 is the only lighting method that allows testing to the exact confirmatory requirements. It also provides added flexibility during forced degradation studies. See PDF file.
That’s a loaded question. There are no “chamber accuracy” specifications as such. The answer requires an understanding of several performance parameters. Control Tolerance- The temperature controller uses an RTD control sensor, which is located in the discharging airflow. Control tolerance is a measure of how much the temperature varies after stabilization at the control sensor. It is a measure of the humidity variations, NOT the absolute accuracy of the readout. The control tolerance specifications for this chamber are +/-1degree C or a total of 2degree C. For example, the temperature setpoint may be -65.0 degrees C. The actual temperature varies between -64degree C & -66degree C. These specifications are for an empty chamber. The addition of a test sample may affect the control variations. In some instances, the test sample will reduce these variations.
Uniformity- Also known as gradients. This is a measure of variation in temperature at different locations throughout the chamber interior, at the same time, after stabilization. The uniformity specification for this chamber is +/-1 degree C or a total of 2 degrees C when measured at least 2” away from the chamber interior walls. These specifications are for an empty chamber. The addition of a test sample may affect the temperature uniformity. For example, an energized test sample will produce a higher temperature near the sample.
Controller Accuracy- This is the ability of the temperature controller to accurately display a temperature measurement when compared to a standard. The controller display accuracy is +/-0.65 degree C, +/-1 LSD. However, the total measurement accuracy in the chamber includes the thermocouple sensor wire accuracy. RTD wire accuracy is +/-1 degree C or 0.75% of reading, whichever is great. Therefore, total system accuracy over the chamber’s typical operating range is typical +/- 1.65degree C, +/- LSD. This is not a measurement of chamber performance.
This chamber uses a closed-loop refrigeration system. Just like your refrigerator at home, it does not need periodic charging. If the charge is low, this means that there is a leak. Leaks should be repaired before recharging.
PLC stands for —- PROGRAMMABLE LOGIC CONTROLLER
Although any artifact will show some sensitivities to both temperature & humidity fluctuations, the response to temperature alone is usually very minor & most artifacts will be stable at a wide range of temperatures. However, artifacts are usually far more sensitive to changes in moisture content. As they gain lose moisture they will often develop internal stresses that may be deleterious. In addition, higher moisture levels may encourage chemical or biological changes.
As the temperature increases, it is able to hold more moisture. As it decreases, it can hold less. The result is that a volume of air that is nearly saturated at a low temperature (high relative humidity ) will be able to hold more moisture as its temperature rises & so will be ‘dryer’. The opposite is true. For this reason, relatively dry air in the winter will form frost on a window or in a freezer.
Stresses resulting from changes in the moisture content, of an object are considered far more dangerous than the minor stresses that may be created with temperature change. For some years now, the prevalent altitude in preventive conservation is to keep the relative humidity around an artifact steady with no concern for small variations of temperature. If the artifact neither gives up nor absorbs water, it will remain dimensionally stable. A constant RH will prevent the exchange of water to & from an artifact.
In our smaller units, humidity is measured in the enclosure on a remote sensor module. The sensor module also contains tiny lights to indicate normal operation as well as various trouble indicators. Larger units use a single dedicated sensor to measure room conditions & apply this to all cases in the system.
No. The air in the distribution system is not “under pressure” in a normal sense. However, in order to move air the tubing, some air “pressure” must be applied. The actual air pressure is extremely small, the output from the delivery tubes is often less than a “breath” & can only be noticed by placing an outlet tube next to your lips.
The use of air pressure will vary according to the installation greater force/pressure is needed to move the air through longer or more narrow supply tubing. The pressure never will be more than a few inches of water column pressure.
In some situations (usually with very well cases) the incoming supply air may, in fact, slightly increase the internal pressure in an enclosure. The “pressurization” is so small that it can have no appreciable effect except to prevent air inflow from the gallery. As the inflow might contain pollutants or might be at an inappropriate humidity level, this is the additional benefit
Calibration services are available for the specialized equipment we manufacture. In some isolated cases, we will calibrate the competitor’s equipment if it is compatible with test fixtures & methods. New Mack equipment is supplied with either a certificate of calibration (if variable adjustments or manufacturing techniques are necessary to bring the equipment into an agreement with NIST traceable standards) or a certificate of conformance (where the equipment meets the published specifications by inherent design), when applicable. (This does not apply to accessory items or subsystems). All calibrated equipment includes a calibration sticker listing the date of calibration, technician’s initials & the suggested re-calibration date which is one year from the calibration data. The MACK test & calibration dept maintains equipment & procedures in accordance with Mil-STD 45662A. this standard has been supported by ANSI/NCSL Z540-/-1994 which is more stringent, however, MACK does not strictly conform to the newer standard calibration date is normally not supplied with new equipment, although this may be requested at the time of ordering at an additional charge(the cost is typically our normal charge for calibration with date). Calibration standards are calibrated yearly or more frequently if necessary. The calibration due dates are tracked & NIST traceability documents are kept on file. Mack calibration system adequately meets the requirements of most of our customers & therefore, we are not seeking independent approvals. In the event, your company requires an in-depth evaluation of our facility, please contact MACK to arrange for a visit by your inspection personnel. The appropriate information will be made available on a case-by-case basis. MACK does not imply or infer compliance with any requirements that are not listed above.
Turn around time is typically 2-3 weeks after receipt of the equipment. Repair time can vary greatly depending on the backlog in the house at any given time. Simple calibration can usually be performed faster than a repair. MACK will make every effort to turn around the equipment as quickly as possible. In some instances, the equipment is delayed due to the lack of a Hard Copy PO or inadequate instructions. Make sure these issues are addressed beforehand if a quick turnaround is desired.
If the moisture content & relative humidity of the air surrounding it are in balance, moisture will neither move into nor out of the object.
Why is temperature control so important? The effects of temperature upon drug photostability can be dramatic. The ICH Q1B guideline correctly describes the need for a temperature-controlled environment in order to isolate thermal effects during photostability testing. The importance of careful temperature control can be illustrated by exploring the influence of temperature upon photochemical reactions.
In most cases, the temperature does not significantly affect the rates of primary photochemical reactions, although photolysis quantum yields can sometimes be influenced. However, many secondary thermal reactions involving, for example, photochemically derived free radicals, have kinetic rate constants that are temperature-dependent. The result is that the photo stabilities of some drug compounds may exhibit little or no temperature dependence, while others may have marked temperature dependence.
In some cases, a drug compound may undergo photodegradation as shown below:
D + hv ® D* (1)
D* ® P (2)
D is the drug molecule, D* the drug molecule in an electronically-excited state as the result of UV or visible photon (hv) absorption. P is the photoproduct or photoproducts.
Step (1) represents photon absorption by the drug molecule.
Step (2) is the transformation of the excited-state drug molecule into a product or product. In this case, the temperature is unlikely to have any significant effect on the photostability of the drug. This is true because the rate of photon absorption and the rate at which the excited state is transformed into products are likely to have no significant temperature dependences.
Consider the following sequence of reaction steps that involve the formation of reactive intermediates and frequently occur during photostability testing of drug molecules:
D + hv ® D* (3)
D* ® R* (4)
R* + A ® P1 (5)
R* + B ® P2 (6)
Again, D is a drug molecule, D* is the drug molecule in an electronically excited state, and R* represents short-lived free radical or other reactive intermediates. The symbols A and B represent two different molecules that are present in the drug formulation, while P1 and P2 are two different photoproducts.
Step (3) represents the absorption of a UV or visible photon (hv)
Step (4) represents the decomposition of the original drug molecule into intermediates, and
Steps (5) and (6) are reactions between the intermediates and two molecules A and B.
The temperatures at which steps (3) and (4) occur do not normally have marked effects upon the rate of photodegradation. As was stated previously, this is true because the rate at which photons are absorbed is not temperature-dependent and the rate at which the excited state of the drug molecule decomposes into intermediates does not usually have a strong temperature dependence. However, the rate at which steps (5) and (6) occur can be strongly temperature-dependent.
In general, the rate of a chemical reaction can be expressed:
Rate = k (CX)(CY) (7)
Where k is the kinetic rate constant, CX is the concentration of reactant X and CY is the concentration of reactant Y. The temperature dependence of the rate constant for a chemical reaction is expressed using the Arrhenius equation:
k = Ae-Ea/RT (8)
Where k is the kinetic rate constant, A is the pre-exponential factor, Ea is the activation energy, R is the ideal gas constant, and T is the temperature. The temperature dependence of the rate constant thus goes as k~e-1/T (See Figure). As a consequence, increasing the temperature increases the rate constant and increases the rate of the reaction. This Arrhenius-type temperature dependence of drug photostability has been observed in a number of studies (2-4).
Returning to the series of steps above, each of steps (5) and (6) represent a reaction between R*, which is a short-lived species (e.g., a free radical), and some molecule present as an active ingredient, inactive ingredient, or excipient in the drug formulation. An increase in temperature can reduce the photostability of the drug (D) by increasing the rates for steps (5) and (6). It is important to note that step (5) involves a reaction of R* with molecule A and step (6) involves a reaction of R* with molecule B, where A and B are different molecules. These steps could well have significantly different temperature dependences.
Consider the reaction step (5) and step (6) above. The rate constants for each of these steps are:
k5 = A6e-Ea5/RT (9)
k6 = A6e-Ea6/RT (10)
The rate constant for step (5) is k5 and k6 is the rate constant for step (6). The rate constants and thus the rates of reaction are different whenever A5 and A6 and Ea5 and Ea5 are different. In other words, the rate of formation and thus, the yield of P1 relative to P2, may be significantly affected by a change in the temperature.
It is important to realize that inability to effectively control temperature during photostability testing is likely to result in an increase in temperature that in some cases may have no effect but when an effect is present is likely to result in an apparent increase in the rate of measured photodegradation. Thus, samples will appear to be less photostable than is actually the case. This will always depend upon the mechanism by which the sample undergoes photodegradation. Unfortunately, elucidating the mechanism is frequently not straightforward.
Example of Temperature Affecting Photostability Testing Results
The drug tretinoin tocoferil used to treat skin ulcers is an example of a substance for which photostability testing results have been shown to be highly temperature-dependent. It was determined by Teraoka, et. al, (3) that the rate constant for the photodegradation of tretinoin tocoferil has an Arrhenius-type temperature dependence.
In some cases, the result of poor temperature control is an alteration of the products or product distributions obtained during photostability testing. This further underscores the need for adequate temperature control during photostability testing.
Limitations of Using Dark Controls to Correct for Temperature Effects
The ICH guideline allows the use of dark controls during photostability testing as a means of evaluating the contribution of thermally induced changes. Dark controls usually consist of samples wrapped in aluminum foil in order to protect them from light exposure. This allows thermally induced changes to be compared with thermally and radiation-induced changes.
Dark controls allow corrections for strictly thermal reactions that occur in the dark and under illumination. However, dark controls never allow correction for reactions in which a photochemical event initiates a secondary thermal reaction. This is why temperature control is essential.
As an example, the measured rate constant for photodegradation of avobenzone, an active ingredient used in sunscreens, was reported by Allen et al., as k = 1.12×10-5 sec-1 in solution (5). Let’s suppose that the actinometry data was in error by 20 percent due to thermal reactions that were not corrected for by the use of dark control. This would result in the actinometry data indicating that the sample had been exposed to 20 percent more radiation than was actually the case and would thus cause the avobenzone to appear to be 20 percent more photostable than it actually is. This is quite a large error.
The effects of photo-initiated thermal reactions such as those observed with the quinine monohydrochloride actinometer are illustrated by the graph shown above. The “irradiated” line represents the rapid drug loss from both photo and thermal reactions occurring simultaneously during photostability testing. The “dark control” is the drug loss due to thermal effects only. The “photo-initiated thermal reaction” encompasses the effects of the dark control and the photo-initiated thermal contribution. Ordinarily, the contribution represented by the “dark control” is subtracted from the ‘irradiated’ data in order to determine actual photostability. But, since the dark control sample is never exposed to irradiation, it never undergoes the photo-initiated thermal reaction.
Consequently, the apparent photoreaction masks the significant contribution of a photo-induced thermal reaction making the drug appear to be far less photostable than it actually is. A more accurate measure of the photoreaction would be to subtract the “photo-initiated thermal reaction” from the “irradiated” data.
Temperature Control is Required for Chemical Actinometry
The quinine monohydrochloride chemical actinometer which is specified in the ICH guideline is the standard method for measuring light exposure during photostability testing has been shown by Christensen et al., to have a significant Arrhenius-type temperature dependence (6). The authors found that the rate of the reaction increased threefold in the temperature range of 25º to 52º C and that the activation energy was 30 kJ/mol, using the Arrhenius equation, as described above. They also found that, for the dark reactions, the change in absorbance was non-linear with respect to time. The rate of the dark reactions was smaller than during light exposure and dependent on the light exposure level prior to the dark reactions. The calculated activation energy of the dark reactions was 18 kJ/mol when calculated, using the Arrhenius equation on the initial reaction rates. They concluded that different activation energies for the light reaction and the dark reaction indicated different degradation pathways for these two reactions. This clearly demonstrates that the use of a dark control is not sufficient and that temperature control is essential when using the quinine monohydrochloride actinometer. Thus, a temperature change of only a few degrees results in a huge error.
Lamp Type Affects Temperature Control
The ICH guideline allows the illumination source to be metal halide, xenon (Xe) arc, artificial daylight (D65) fluorescent, or a combination of UVA (black light) and cool white fluorescent lamps. An important advantage enjoyed by fluorescent lamps (also Option 2) is that temperature control is relatively easy compared to temperature
control with Option 1 when metal halide or Xe arc lamps are used. This is true because a large portion of the energy emitted by metal halide and Xe arc lamps is in the form of heat. Temperatures of 25ºC or lower are not always attainable during photostability testing when Xe or metal halide equipment is used. Fluorescent lamps emit significantly less heat. As a consequence, temperature control is much simpler when fluorescent lamps are used.
In some cases, it may be desirable to measure the photostability of a drug substance
at refrigeration temperatures (5ºC). In this application, fluorescent lamps have been effectively used to maintain a low-temperature controlled environment. This would be much more difficult using Xe arc or metal halide lamps.
Elevated temperatures during drug photostability testing in which drug samples are in capsules can, and frequently does, lead to melting of the capsules and a big mess!
While humidity control is not specifically addressed in the ICH guideline, the state of hydration affects the photostability of some samples (7). The same drug substance subjected to identical irradiance and temperature conditions can yield very different results when exposed to different humidity levels during testing. When product presentation is such that samples are exposed to ambient (chamber) air, the effects of humidity must be considered.
Photostability testing of drug substances in liquid solutions is typically carried out using sealed quartz containers. The humidity of the air in the photostability chamber is of no consequence in these cases. The relative humidity of the air surrounding samples during photo-stability testing can affect the results of these tests when powdered solids or solid tablets are being illuminated in open containers. Relative humidity can affect the degree of hydration for any of the ingredients present in the drug formulation. This can alter the light absorption and reflection characteristics of the sample leading to changes in observed photostability.
When a drug substance is formulated into tablets, photodegradation may occur rapidly at first but then slow significantly once the drug molecules at the surface have undergone photodegradation. In some cases, the photoproducts formed near the surface of the tablet actually shield the drug molecules present in the interior of the tablet from photodegradation. Powdered drug substances are exposed more uniformly to the light source and may degrade more rapidly than tablets. Humidity issues would also be expected to be more important when powders are being tested than when tablets are tested. Again, this is true because powders experience a much greater exposed surface area than tablets and can absorb more water. This makes the humidity control issues discussed above particularly important when testing powders.
Many drug substances undergo some degree of hydrolysis (reaction with water). In some cases, high relative humidity during photostability testing of powders or tablets may lead to hydrolysis reactions. This can affect the kinetics of photodegradation reactions; particularly if there are regions on the surface or within the solid where large numbers of water molecules are present. If the products of any hydrolysis reactions absorb UV or visible radiation, this could potentially cause a change in measured photostability for the drug compound. Most hydrolysis reactions can be represented by the following equilibrium:
D + H2O A + B (11)
D is a drug molecule and A and B are hydrolysis products. Hydrolysis reactions occur in the dark and thus any loss due to hydrolysis also occurs in the dark control sample. However, if either A or B absorb UV or visible radiation, they may undergo photodegradation. When this occurs, the equilibrium above is shifted so that more drug (D) undergoes hydrolysis resulting in an apparent decrease in photostability. Further, when A or B undergo photo-degradation, free radicals or other reactive intermediates may be formed which can react with the drug (D) further decreasing apparent photostability:
D + H2O A + B (12)
A + hv ® R* (13)
B + hv ® R* (14)
R* + D ® P (15)
Another potentially important issue associated with humidity control is the potential for oxygen (O2) to dissolve in hydrated regions of powders or tablets. Oxygen has a relatively high solubility in aqueous environments. Any component of the drug formulation that absorbs UV or visible radiation can potentially transfer energy to O2 molecules yielding powerful oxidants such as singlet molecular oxygen (1O2) or superoxide radical anion (O2.-). These oxidants can react with the drug molecules further decreasing apparent photostability:
D + H2O A + B (16)
A + hv ® R* (17)
B + hv ® R* (18)
R* + D ® P (19)
R* + O2 ® R + 1O2 (20)
1O2 + D ® P (21)
where reactive intermediates (R*) are formed as before which then can either react with the drug molecules directly as in step (19) or react with oxygen forming 1O2 in step (20) which then reacts with the drug molecule in step (21). The reaction of 1O2 with the drug substance consumes the drug and decreases photostability. Uncontrolled, humidity can alter photostability testing results and cloud their interpretation.
Example of Humidity Affecting Photostability Testing Results
When titanium dioxide (TiO2) is used in tablet formulation, relative humidity control during photostability testing can be especially important. When properly formulated, TiO2 is effective at reflecting and scattering UV and visible radiation and represents an effective way to reduce the photodegradation of drug compounds in tablets. Unfortunately, TiO2 also acts as a photocatalyst. When this occurs, TiO2 can increase the rate of drug photodegradation. The solid-state photocatalytic activity of TiO2 is dependent upon relative humidity. Consequently, the rate of drug photodegradation in tablets formulated using TiO2 can be significantly increased by increasing relative humidity (6). In an aqueous environment:
TiO2 + H2O + hv ® ÝOH (22)
D + ÝOH ® P (23)
OH is the hydroxyl radical, a very powerful oxidant that can react with virtually any organic compound. Reaction with ÝOH consumes the drug and decreases apparent photostability. Accordingly, humidity control is very important when conducting photostability testing of TiO2 coated tablets.
As an example, Kakinoki et al., (8) found that the photostability of mequita-zine was especially dependent upon relative humidity. The relationship between the apparent degradation rate constant and water vapor pressure was found to be described by a simple power law.
The major photodegradation products of mequitazine resulting from the photocatalytic activity of TiO2 were mequitazine-S-oxide and mequitazine-sulphone. Degradation of mequitadine increased with the addition of TiO2 and its photocatalytic activity was found to be controlled by water vapor pressure (i.e., relative humidity). The photodegradation of mequitazine with TiO2 was found to follow a different photodegradation pathway from mequitazine without TiO2 yielding different products. Thus, control of relative humidity is essential in a variety of circumstances.
Photostability Chamber with Proper Temperature and Humidity Control
A properly designed photostability chamber will both control temperature and ensure good temperature uniformity throughout the entire sample placement area. Typical chamber conditions are maintained at ±0.2ºC temperature control and ±2ºC temperature uniformity with lights on full power. The graph below shows the temperature uniformity of 25 ± 2°C across a 20 inch (508mm) wide by 23 inches (584mm) deep shelf at 36klux.
For situations where control of relative humidity is needed while performing photostability testing, humidity control can be integrated into chambers. Typical relative humidity control is ±3%.
Conclusions
Appropriate temperature and humidity control during drug photostability testing are important considerations. Allowing the temperature to increase can lead to a decrease in apparent photostability. Poor temperature control can also lead to serious errors that are in some cases not corrected by the use of dark controls. This is especially problematic with chemical actinometers like quinine monohydrochloride. When solid samples are in open containers, allowing the relative humidity to increase can cause an apparent decrease in photostability. These errors can result in a tested drug substance appearing to have poorer photostability than is actually the case. For these reasons, the use of a photostability chamber that allows the user to control both the temperature and the relative humidity is highly recommended.
References:
- International Conference on Harmonization (ICH) Guidelines for the Photostability Testing of New Drug Substances and Products, Federal Register, 62, 27115-27122 (1997).
- Monti, S., et al., in Drugs Photochemistry and Photostability, Albini, A., Fasani, E., eds., Royal Society of Chemistry, p. 150-161, (1998).
- Teraoka R, Konishi Y, Matsuda Y, Photochemical and Oxidative Degradation of the Solid-state Tretinoin Tocoferil. Chem. Pharm. Bull. (Tokyo), Vol. 49 (4), 368- 372 (2001).
- Matsuda Y, Masahara R., Photostability of Solid-state Ubidecarenone at Ordinary and Elevated Temperatures Under Exaggerated UV Irradiation. J. Pharm Sci., Vol. 72(10), 1198-203 (1983).
- Allen, J.M., Allen, S.K., Lingg, B.: “Photostabilities of Several Chemical Compounds Used as Active Ingredients in Sunscreens”, in Drugs: Photochemistry and Photostability, Albini, A. ed., Royal Society of Chemistry, Cambridge, UK, 1998.
- Christensen K., Christensen J., rFrokjae S, Langballe P, Hansen LL, Influence of Temperature and Storage Time After Light Exposure on the Quinine Monohydrochloride Chemical Actinometric System. Eur. J. Pharm. Sci., Vol. 9(3), 317-21 (2000).
- J. Piechocki, “Pharmaceutical Photostability Testing Protocols” presented at CBI’s Design and Qualify Photostability Studies in Stability Testing, June 2001.
- Kakinoki K, Yamane K, Teraoka R, Otsuka M, Matsuda Y., Effect of Relative Humidity on the Photocatalytic Activity of Titanium Dioxide and Photostability of Famotidine. J. Pharm. Sci., Vol. 93, 582-9 (2004).
- Robert W. Dotterer is an applications engineer for Caron Products & Services Inc. (Marietta, Ohio), and John M. Allen, Ph.D., is an associate professor of chemistry at Indiana State University (Terre Haute, Ind.). Reach Dotterer at bdotterer@caronproducts.com or 740-373-6809. Reach Allen at challen@isugw.indstate.edu or 812-237-2234
When we perform an environmental test on a sample of equipment, we simulate one or more environments that may be harmful to that equipment. This should be done during the development of a new product. Our aim is to increase the reliability & durability of that new product. Call that sample our DUT or Device Under Test.
We can place our DUT in a climatic environmental chamber for a climatic test. There we will stress it varying altitude, temperature & humidity. In other chambers, we can stress it with sand & dust, with salt, fog, sunshine, etc to simulate in service or in transport conditions.
A test in which the air surrounding a test specimen is raised or lowered to pre-determined levels. The purpose is to observe the effect of the temperature extremes on the equipment, which may be operating or non-operating. Temperature extremes
and rapid temperature transitions are also used to purposely induce failures to determine weak points or latent defects.
A humidity test simulates the moisture-laden air found in tropical regions. There are typically two types of humidity tests, condensing and non-condensing. Condensing humidity tests consist of temperature cycling in high relative humidity air. The temperature cycling induces the moisture to condense on all surfaces of the test specimen. Additionally, the temperature cycling causes the test specimen to “breathe”, pulling moisture-laden air inside; it then condenses to liquid form. This is an extremely severe test for electronics. Non-condensing humidity tests are run at a constant temperature, with high relative humidity, typically greater than 95%. This test is not as severe as the condensing test because the moisture is not in liquid form. This test is much more difficult to perform because the temperature must be tightly controlled to prevent condensation at such a relative humidity.
The relative humidity is the amount of humidity or water vapor in the air, relative to how much the air hold at that temperature, expressed as a percentage. The total amount of water vapor that air can hold is a function of temperature, the hotter the air is the more water vapor it can support.
A thermocouple is the world’s most popular transducer for measuring temperature. It works by generating a small millivolt electrical signal when a temperature difference exists between the two end junctions of a pair of dissimilar metals. One end of the thermocouple is fused together to form measuring (or hot) junctions & the other end, the cold (or reference) junctions, is connected to the measuring instrument such as a data logger.
As the temperature increases, it is able to hold more moisture. As it decreases, it can hold less. The result is that a volume of air that is nearly saturated at a low temperature (high relative humidity) will be able to hold more moisture as its temperature rises, & so will be ‘dryer’. The opposite is true. For this reason, relatively dry air in the winter will form frost on a window or in a freezer.
Stresses resulting from changes in the moisture content, of an object are considered far more dangerous than the minor stresses that may be created with temperature change, for some years now, the prevalent attitude in preventive conservation is to keep the relative humidity around an artifact steady with no concern for small variations of temperature. If the artifact neither gives up nor absorbs water, it will remain dimensionally stable. A constant RH will prevent the exchange of water to & from an artifact.
Audit Trail initiation requirements differ for data vs. textual materials. For data: If you are generating, retaining, importing, or exporting any electronic data, the Audit Trail begins from the instant the data hits the durable media. For textual documents: if the document is subject to approval and review, the Audit Trail begins upon approval and release of the document.