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In the pharmaceutical industry, maintaining the stability and efficacy of drug formulations is a critical challenge. Issues such as batch-to-batch variation, amorphous content, and hygroscopicity can significantly impact the quality and performance of pharmaceutical products. Dynamic Vapour Sorption (DVS) technology has demonstrated its use as a vital tool for scientists in the pharmaceutical field, offering precise measurements and valuable insights into moisture interactions.
The DVS method for measuring moisture sorption on pharmaceutical materials involves placing a prepared sample in a microbalance chamber where the relative humidity (RH) is precisely controlled. The process begins with stabilizing the sample at a low RH to establish a baseline mass. Subsequently, the RH is incrementally increased, and the sample is allowed to equilibrate at each step until a stable mass is recorded. This continues until the maximum target humidity is reached, followed by a desorption phase where the RH is gradually decreased. Throughout this process, the DVS records the mass changes, enabling the generation of sorption and desorption isotherms that plot the equilibrium moisture content against RH (Figure 1). These isotherms are crucial for analysing hygroscopicity, detecting hydrate formation, quantifying amorphous content, and identifying moisture-induced phase transitions.
DVS Resolution
The precision and sensitivity of DVS, along with its ability to provide detailed and rapid measurements, make it an invaluable tool for understanding and controlling the moisture interactions of pharmaceutical materials.
Figure 1. A schematic of the DVS method
Figure 2. The determination of amorphous content of a pharmaceutical material using the DVS
Batch-to-batch variation is a common issue that can arise due to differences in processing conditions during synthesis. Even minor variations can lead to significant differences in the moisture sorption properties of pharmaceutical materials. The DVS has been used to measure moisture sorption properties of two batches of a hydrophobic drug at 25 °Cover a humidity range of 0-95% RH. The DVS instrument was able to differentiate between the two batches, which had moisture uptakes of 0.055% and 0.070% at 95% RH, respectively. This small difference highlights the precision of DVS in identifying and quantifying batch variations, ensuring consistent product quality.
Amorphous content in pharmaceutical materials can lead to unpredictable behaviour, affecting stability and efficacy. Amorphous materials tend to absorb more moisture, which can induce phase transitions and degrade the product. The DVS provides a reliable method to quantify amorphous content by analysing moisture sorption isotherms.
By calibrating known amorphous contents or identifying a vapor that induces crystallisation, the DVS helps scientists understand the extent of amorphous phases in their materials and make informed decisions to mitigate associated risks. The example shown presents data where crystallisation of a pharmaceutical ingredient was induced using ethanol as a solvent (Figure 2). After establishing a baseline, the system was adjusted to a low partial pressure environment before initiating crystallisation at 30% p/p0. To induce a phase change, ethanol concentration was then increased to 85% p/p0, resulting in the formation of a crystalline material. Due to the formation of a structured crystalline lattice, there was a reduced uptake of ethanol when the system returned to 30% p/p0 in the third stage of the experiment. The amorphous content was calculated based on the difference in ethanol uptake between the first and third steps of the experiment. These studies can be used to enhance the stability and shelf life of pharmaceuticals by identifying and controlling the less stable amorphous regions, thereby preventing unwanted phase transitions.
Hygroscopicity, or the ability of a substance to absorb moisture from the air, can cause significant issues in pharmaceutical formulations. The formation of hydrates and excessive moisture uptake can alter physical properties.
Approximately one-third of all active pharmaceutical ingredients (APIs) can form crystalline hydrates, impacting their stability and performance. The DVS is instrumental in detecting and characterising hydrate and solvate formation. For example, the DVS was used to investigate the hydrate formation of nedocromil sodium, a versatile medication primarily used in the prevention and management of asthma.
Nedocromil sodium monohydrate has the potential to form trihydrates and heptahemihydrates due to its hygroscopic nature and the availability of multiple sites for water molecule interaction within its crystalline structure. These forms can have significant repercussions in pharmaceutical applications as they may exhibit different dissolution rates compared to its anhydrous form, affecting the drug’s release profile and therapeutic efficacy. The DVS measured changes in sorption behaviour at 25 °C from 0-95% RH in 10% steps. The data was then converted to an isotherm plot where both adsorption and desorption branches were observed.
This simple conversion identified three hydrate forms during adsorption showing that the trihydrate form was stable between 20% RH and 90% RH, and that heptahemihydrates formed under conditions above 90% RH. During desorption, the material retained its hydrated species and reverted to monohydrate directly with no trihydrate reformation (Figure 3). This study is particularly useful in identifying the specific conditions under which hydrates form or convert between different states. Pharmaceutical scientists can therefore develop strategies to mitigate adverse effects, ensuring consistent drug performance using the DVS.
Figure 3. Moisture sorption of nedocromil sodium at 25 °C from 0-95% RH in 10% steps showing the DVS mass change plot and its corresponding
Moisture-induced degradation is a significant concern in the pharmaceutical industry, leading to reduced drug efficacy and shelf life. DVS, combined with its camera accessory can capture pictures insitu at multiple stages of the experiment. It can provide a comprehensive understanding of moisture-induced degradation mechanisms.
The example shows a DVS ramping experiment on spray dried lactose. A ramping experiment begins with obtaining a stable baseline before increasing the RH by 10% per hour up to 90% RH (Figure 4). Phase changes are observed starting with moisture adsorption on the surface of the material. Lactose undergoes a glass transition stage with increasing RH, where moisture penetrates the bulk. When lactose transitions from a glassy to a rubbery state due to increased humidity, its molecular mobility increases.
Figure 4. Ramping experiment of spray dried lactose from 0-90% RH at a rate of 10% RH per hour showing a phase change through the glass transition stage with sample photos at each stage
This heightened molecular mobility facilitates the rearrangement of lactose molecules into a more thermodynamically stable crystalline form. The absorbed moisture acts as a plasticiser, promoting recrystallisation which occurred above 80% RH. Further increase in RH resulted in the decomposition the material. By analysing how moisture interacts with pharmaceutical substances at different humidity levels, scientists can develop strategies to enhance the stability and longevity of their products.
Determining amorphous content, understanding hygroscopic properties, identifying hydrate forms, and analysing moisture induced degradation are just a few capabilities of the Dynamic Vapour Sorption technology. It has been proven to be an indispensable tool for scientists in the pharmaceutical industry. Its ability to precisely measure and analyse moisture interactions gravimetrically helps overcome challenges and provides critical insights into moisture-related behaviour, improving the understanding of the stability, efficacy, and quality of drug formulations. For any pharmaceutical laboratory aiming to achieve consistent and reliable results, incorporating the DVS into their analytical routine is a necessary step towards providing a greater understanding in pharmaceutical development and production.
Surface Measurement Systems has been a global leader in gravimetric sorption analyzers for over 30 years. Founded by Prof. Daryl Williams in 1991, we revolutionized solid characterization with our Dynamic Vapor Sorption (DVS) technique.
We delivered our first DVS instrument to Pfizer in 1992 and introduced the first commercial Inverse Gas Chromatography (iGC) instrument in 2002. Today, Surface Measurement Systems sets the industry standard for sorption research, partnering with leading companies in pharmaceuticals, food, fine chemicals, aerospace, energy, catalysts, and more. We work with leading companies across various industries, offering world-class support and innovative solutions. Our commitment to integrity, professionalism, and continuous improvement makes us the top choice for sorption research worldwide.
