The stability of active compounds in an excipient, and the process of storing the compounds without degradation, are the major concerns related to the development of new pharmaceutical products. Moisture sorption resulting in polymorphism or the formation of amorphous structures may affect dissolution kinetics and contravene licensing conditions. These effects can prevent certification of new medicines.
This article demonstrates the analysis of moisture sorption of pharmaceuticals using the IGAsorp instrument.
Experimental Method for the IGAsorp instrument
This experiment was performed using an IGAsorp Gravimetric Vapour Sorption (DVS) instrument shown in Figure 1. The instrument performs isothermal measurements at atmospheric pressure at relative humidity (RH) in the range of 0-98% RH, measuring changes in weight due to absorbed vapor, with high resolution (to 0.05 mg). Bubbling 99.999% pure dry nitrogen through distilled water provides a 100% humidity gas stream, which is then combined with a dry nitrogen stream to provide the desired RH. This mixture is passed over the sample at 100 ml/min.
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Figure 1. IGAsorp Gravimetric Vapour Sorption
Isotherms can be determined with a temperature stability of ±0.05°C. Kinetic data related to each isotherm point is recorded at intervals down to 0.1 seconds. The IGAsorp software allows analysis in real time to identify the asymptotic equilibrium point. This enables the instrument to record the predicted value and move on to the next RH set-point upon satisfying the user-defined criteria. Following this, an isotherm is plotted over the selected RH range using the equilibrium points.
Sorption Analysis Using Aspirin
The IGAsorp was used to test an aspirin tablet at 37°C in the range of 0-95% RH. The tablet out from its package and placed in a gas-permeable steel mesh container to allow vapor to contact with all the surfaces. The sample was then exposed to a humid gas stream at 100 ml/min. The sample was then dried in the dry gas stream overnight at 115°C before isotherm measurement.
Results and Discussion
Figure 2 shows the moisture sorption isotherm of the blister pack and aspirin tablet. It was observed that the aspirin absorbed 2.24 wt. % of water at 95% RH. The uptake kinetics seemed to be limited by the passage of water through the excipient. Figure 3 shows the uptake kinetics for the aspirin tablet during the 40 to 50% RH isotherm step.
The aspirin was observed to absorb 840 µg of moisture over a 4.8 hour period, after which the uptake reached 99 % of the asymptotic value. This suggests that the medicine may be altered when exposed to moisture for a short period of time (<30 min), meaning it is necessary to choose, and appropriately test, a protective packaging to prevent exposure. The moisture sorption isotherm for the blister pack (figure 2) shows that the permeation of moisture can be resisted well, and more effectively than the aspirin tablet, but not completely. A noteable gain in wt. % occurs over 40% RH.
Figure 4 shows water permeation taking place at high humidity levels over 24 hours. It can thus be concluded that highly moisture-sensitive medicines are not compatible with the blister pack in question at above 40% ambient humidity.
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Figure 2. Moisture sorption isotherms for an aspirin and its blister pack
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Figure 3. Kinetic sorption data recorded on the aspirin tablet for the adsorption point from 40% to 50% RH
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Figure 4. The permeation of moisture through a blister packet containing an aspirin tablet
Conclusion
This study has demonstrated the process of accurately determining moisture sorption uptake by pharmaceutical products and packaging using the IGAsorp instrument. This information allows the assurance of safety and longevity of medicines under different climatic conditions.
This information has been sourced, reviewed and adapted from materials provided by Hiden Isochema.
For more information on this source, please visit Hiden Isochema.