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The water vapour or moisture sorption properties of pharmaceutical materials such as excipients, drug formulations and packaging films are recognised as critical factors in determining their storage, stability, processing and application performance [1,2]. According to the US Pharmacopeia, moisture is not treated as an impurity, but water in a drug substance should be monitored and controlled as strictly as possible. (USP general chapter 1241). Further, the moisture content affects crystallinity and influences storage modulus, permeability, density and melting point of pharmaceutical products. For amorphous materials, moisture can significantly alter the glass transition temperature, and even initiate spontaneous transformation to the crystalline form. Additionally, water facilitates hydrolysis and induces drug degradation. Finally, water content is routinely used in determining the dry and solvent-free assay value of a drug substance [3].
For the above reasons, a rapid, highly- sensitive and automated method to study moisture sorption properties is desired. Today, the DVS is widely used across numerous industries for investigating the vapour sorption properties of solids, fibres, gels, particulates, and composite materials. This application note summarises several DVS applications related to drugs, excipients, and pharmaceutical ingredients.
Dynamic Vapour Sorption (DVS) has long been used for investigating the interaction of water vapour with active pharmaceutical ingredients (API’s), excipients and pharmaceutical formulations. This article summarises several examples of using DVS for pharmaceutical-related applications including: hygroscopicity, moisture content, moisture-induced phase transitions, hydrate formation/loss, and amorphous content.
The instrument measures the uptake and loss of vapour gravimetrically using the SMS Ultra Balance with a mass resolution of ±0.1 μg.
The vapour partial pressure around the sample is generated by mixing saturated and dry carrier gas streams using electronic mass flow controllers. In addition to controlling water vapour pressure (i.e. relative humidity), the DVS models from SMS have the unique capability to actively measure and control the concentration of a wide range of organic vapours. This is accomplished by the addition of a patented Speed of Sound sensor in most of the advanced models with organic capabilities. This technology allows the instrument to measure and control water and organic vapour concentrations in real time.
DVS Resolution Dual Vapour Gravimetric Sorption Analyzer
The DVS family of instruments has been routinely used in number of pharmaceutical applications which includes:
Moisture Content/Sorption Isotherm
The DVS family of instruments is commonly used to determine moisture content isotherms. This is accomplished by exposing the sample to a certain relative humidity until equilibrium has been established.
Then, this is repeated at numerous RH steps until a complete sorption and/or desorption isotherm has been established.
Hygroscopicity of API’s
Measuring the ability of solids to take up water vapour from the atmosphere at constant temperature with changes in RH is often referred to as a measure of hygroscopicity. This measurement is now a routine preformulation activity intended to provide an early assessment of the potential effects of moisture on the physical and chemical properties of drug candidates [4].
Although the usefulness of classifying hygroscopicity in terms of definitive sorption capacities is debatable, several attempts have been made. Also, it is important to note that defining hygroscopicity is only the first step in assessing the potential deleterious effects of moisture on API and formulation solid-state properties. With the above in mind, the European Pharmacopeia has classified the hygroscopic nature of materials as a function of the percent water uptake at 25 °C and 80% RH [5].
Hydrate/Solvate
The ultimate hydration state of a pharmaceutical material may influence several physico-chemical properties including physical and chemical stability [6]. For instance, some hydrated materials become amorphous upon dehydration. Also, different hydrate forms can affect the material solubility, dissolution rate, flowability, and compressibility. The DVS can be used to detect and characterise hydrate formation as a function of environment relative humidity.
Moisture-Induced Phase Changes
Amorphous solids often absorb relatively large amounts of water vapour compared to their corresponding crystalline phases. Sorbed water can act as a plasticising agent, thus significantly lowering the glass transition temperature causing spontaneous phase transitions and lyophile collapse. In fact, there is often a critical humidity at which the glass transition will occur at room temperature.
In addition, this can lead to increased cohesiveness, powder caking and adhesion to other surfaces.
Amorphous Content
The presence of the amorphous phase can yield unique challenges in the formulation, processing, and storage of these materials. Amorphous materials typically have a higher surface area and vapour affinity than their crystalline counterparts.
For vapour sorption methods a calibration of known amorphous contents is typically necessary. Then, the equilibrium vapour uptake at a particular vapour concentration is plotted versus the known amorphous content.
Video Microscopy
The physical changes inferred from the gravimetric data can be further supported by in- situ microscopic images collected during the experiment.
This is done using the DVS-Video accessory. The long-working distance digital microscope allows the automatic collection of images during a DVS experiment with magnification up to 200X.
Raman/Near-IR
Vibrational spectroscopic techniques, such as Near-IR and Raman spectroscopy have also been combined with gravimetric sorption methods.
As moisture is absorbed by a sample, the intermolecular structure and forces within it adapt to accommodate water molecules.
Diffusion/Flux Experiments
Real-time mass change data can be collected as frequently as once every second, which allows the determination of diffusion coefficients for various geometries. DVS has been successfully used to measure diffusion coefficients for films, powders, and fibres. Diffusion into films can be particularly useful for packaging applications.
Water Vapour Transmission Rates (WVTR)
A novel Payne style diffusion cell was designed and developed to measure the permeability/rate of diffusion of a thin film., all within the same setup of a DVS equipment.
BET Surface Area
The BET surface area can also be determined using organic vapours in the DVS. Measuring surface areas via DVS has a few advantages over volumetric techniques.
First, the DVS experiments are performed at atmospheric pressure and room temperature, as opposed to vacuum and cryogenic temperatures.
Sorption Mechanisms
Often it is important to know the vapour sorption mechanism on pharmaceutical related materials to further understand the interaction between vapours and solid materials.
The heat of sorption measurements on α-lactose monohydrate as a model pharmaceutical excipient using water and 1-butanol is an example to demonstrate significant information about the sorption mechanism in a solid-vapour system.
Utilising the functionality of Dynamic Vapour Sorption instrumentation allows the vapour sorption characteristics to be studied on API’s, excipients, final formulations, tablets, capsules, and packaging materials. Water sorption on these materials can be vital in understanding material stability and performance.
This overview application note only summarises a handful of these applications, but hopefully illustrates how DVS technology could be applied to a wide range of pharmaceutical-related materials and challenges.
For complete application note: https://www.surfacemeasurementsystems.com/app-101-moisture-sorption/#popmake-34385
About Surface Measurement Systems (India Operation):
Surface Measurement Systems started their direct operation in India since 2018 named as SMS Instruments Pvt Ltd with its registered office at Hyderabad and we will soon be opening a contract research laboratory named Particle Characterisation Laboratory Private Limited based at Hyderabad to cater to the needs of Particle characterisation under one roof.
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