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Determining amorphous content using dynamic vapor sorption (DVS) is an important analytical technique that provides valuable insights into the stability and performance of materials, particularly in the pharmaceutical industry. Amorphous materials lack the ordered structure found in crystalline materials making their behaviour less predictable with regards to solubility, stability or shelf life. Their presence, even in small amounts can significantly impact, storage and performance of materials since they are more prone to physical and chemical changes over time compared to crystalline materials. The presence of amorphous materials in pharmaceutical active ingredients (APIs) can be detrimental due to their unpredictable and unstable nature, leading to greater variability in properties such as solubility, dissolution rates and stability.
In API manufacturing processes which may include processes like milling, spray drying or freeze drying, amorphous regions can form and become encapsulated in the crystalline matrix of the API. These amorphous regions can represent less than 10% of the volume of the material which is usually the case yet their presence can significantly alter the behavior of the drug. For that reason, there is a need to determine the amount of amorphous content within various pharmaceutical products, as this will greatly affect the quality and performance in a considerable manner.
The amount of amorphous substance can be detected and quantified using a number of analytical methods like DSc, XRPD and NMR, which have been developed over the years. Still today, these techniques have their limitations, for instance, the techniques are not useful in detecting small quantities of amorphous material. On the other hand, the DVS allows using small quantities of sample. DVS allows determining amorphous contents as low as 0.5 percent w/w which is one of the most valuable features for this application in the pharmaceutical industry.
Dynamic Vapor Sorption (DVS) is a state-of-the-art gravimetric measurement tool used to measure the amount of vapor absorbed or desorbed by a material, providing valuable insights into its moisture interaction properties. It is a particularly useful technique that can be used to measure amorphous content in materials by analysing their moisture uptake behaviour, as amorphous regions typically absorb more moisture than crystalline regions under controlled conditions. The general concept of DVS is to determine the change in the weight of a materialas it interacts with a controlled environment of varying humidity or solvent vapor.
Recrystallization
By precisely monitoring the sample’s weight as it absorbs or desorbs vapor at different humidity levels, the DVS provides insights into the material’s sorption isotherms, moisture content, and kinetics. This technique is particularly useful for understanding water sorption behaviour, assessing hygroscopicity, and characterizing amorphous versus crystalline content in materials.
In DVS, there is a well-published approach for measuring the amorphous content of DVS materials. This technique is based on measuring the solvent uptake by the sample before and after the crystallization processes using a solvent that induces crystallization.
The method is very specific as even minute quantities of amorphous material therein have great chances of being detected.
This method is particularly beneficial for assessing the quality and shelf life of pharmaceutical products, as it helps identify and manage unstable amorphous regions that can compromise their efficacy.
The first step consists of the drying phase where the sample is subject to controlled temperature conditions and a continuous flow of carrier gas, which effectively removes any pre-existing moisture and adsorbents which ensures that the measurements reflect only the sorption behaviour of the material itself. This controlled environment helps to stabilize the sample by eliminating variables that could interfere with subsequent sorption or desorption measurements. By achieving a uniform baseline moisture level, researchers can more accurately quantify the material’s moisture sorption isotherms and gain insights into its hygroscopic properties.
To determine amorphous content, the sample is first exposed to this solvent under partial pressures that do not induce a phase change allowing the characterization of its amorphous state. The system then increases the solvent concentration to a specific level that promotes crystallization. A phase change occurs, resulting in the formation of a crystalline structure. By measuring the differences in vapor uptake before and after this crystallization process, researchers can quantify the amount of amorphous content present in the sample. The reduced vapor absorption following crystallization indicates the transition from an amorphous to a crystalline state, providing valuable insights into the stability and behaviour of the material.
There is a direct physical application of the DVS technique within the frameworks of the study on the corticosteroid drug – Fluticasone Proprionate, which is largely used for management of asthma and other respiratory conditions. There are always problems with solubilization of Fluticasone Propionate and therefore it is always necessary to efficiently evaluate and quantify the amorphous content to ensure the solubility and bioactive properties of the drug.
In this study, Fluticasone Propionate was analysed using the DVS using ethanol to induce crystallisation of the material. During the first phase, it was observed that the material showed the existence of non-crystalline areas which absorbed substantially higher amounts of the ethanol vapor than the crystalline areas. These non-crystalline areas were observed to undergo some crystallization upon contact with ethanol leading to a marked decrease in the solvent uptake during the post crystallisation phase. From the final evaluation, it was possible to determine that the sample contained 6.3 % w/w of the amorphous portion.
The above case study illustrates the efficiency and specificity of DVS in detection of amorphous volume percentage in pharmaceutical excipients. The accurate measurement of amorphous content is critical in the case of Fluticasone Propionate, since the stability and performance of a drug in a crystal form is exceedingly affected by the drug’s amorphous volume content.
Dynamic vapor sorption (DVS) is the dominant method used for the measurement of amorphous content in pharmaceutical materials. Due to its remarkable specifications, DVS helps pharmaceutical companies to determine the amount of amorphous regions, contributing to the stability, effectiveness, and compliance of the product. It is likely that as the pharmaceutical industry progresses, the capacity to measure and control the content of amorphous regions will be of paramount importance in the successful development and marketing of drug products.
DVS has raised the bar on the sensitive and robust measurement of amorphous content in pharmaceuticals to a new level and generated relevant information with respect to drug formulation and performance optimization.
To find out more about the diverse applications of Dynamic Vapor Sorption in the Pharmaceutical space, go to www.surfacemeasurementsystems.com, or visit them on their booth at CPHI & PMEC India 2024 on stand RH.K63.
