Wetting is the ability of water, or more generally, solvents and solutions, to spread to some extent on surfaces in pharmaceutical systems. Pharmaceutical systems include drug substances, raw materials, and intermediates such as mixtures, formulations, all dosage forms, packaging materials, and devices. In the most direct form of assessing wetting properties, a drop of the test liquid is placed on the surface of the test material (usually solid) and the spread of the drop is observed optically. The wetting properties of pharmaceutical systems are important for manufacturing, dosage form performance, and stability.
The purpose of the standard “USP 1243 Wetting properties of pharmaceutical systems” published by the American Pharmacopeia (USP) is to provide general information on the wetting properties of pharmaceutical systems, describe experimental techniques used in pharmaceutical practice, identify difficulties with measurements, and discuss approaches used to manipulate wetting properties.
Wetting properties of pharmaceutical systems have many applications, including, but not limited to, raw materials, manufacturing, dosage form performance and stability, devices, and packaging.
When the wetting properties of raw materials are critical to a formulation and manufacturing process, these properties can be measured as part of the materials characterization. In the exploration of solid forms of a drug substance, it may be found that some powders are hydrophobic and exhibit poor wetting properties. It may also be found that poor powder wetting is due to a crystal morphology in which the predominant crystal surface is hydrophobic. In this case, it may be possible to develop a crystallization process that produces a particle morphology with a prominent hydrophilic surface to improve wetting. The wetting properties of the drug substance in a formulation can also be important, particularly in solid dosage forms (e.g., tablets) and suspensions. Similarly, the wetting properties of excipients used in formulations can be relevant to the processing and performance of the dosage forms. The importance of the wetting properties of raw materials is discovered during the development process. The wetting properties of excipients can be seen to affect formulation stability, processing, and performance. When wetting properties are critical, evaluating wetting properties can be part of the materials specification.
Wetting issues in packaging materials and devices (such as container walls, stoppers, and syringe barrels) can lead to dose inhomogeneity. For example, in a metered-dose inhaler suspension of micronized medication, inadequate wetting of particles by the medium can result in particle deposition on the device or primary packaging components, resulting in unacceptable dose delivery from the device. Leakage and extraction fluids can also be affected by the wetting properties of the device or packaging materials.
The key parameter that can be measured experimentally to quantify wetting is the contact angle, shown in the figure. The contact angle is the angle between lines tangent to the liquid-air and solid-liquid interfaces at the three-phase solid-liquid-air boundary. Broadly speaking, a contact angle of 90 degrees or less is considered wetting, while a contact angle of 90 degrees or less is considered non-wetting. The term "spreading" is used for the extreme case of wetting when this angle is 0 degrees.
According to Young's equation, the surface tension of liquids is a key factor affecting wetting. At the surface of a liquid, molecules are subject to unbalanced intermolecular forces, with a stronger attraction toward the interior than in the air. Consequently, the molecular density at the surface is lower than in the bulk, resulting in an increased average separation distance, which leaves the molecules in tension, with the surface area contracting to the minimum possible value, like a stretched membrane. At a junction where the surface of a liquid contacts another material, such as the wall of a container, the surface exerts a force on the material along the line or curve of contact. Surface tension is an intensive property, meaning it is a force per unit length, and the total force is the perimeter or total contact length. Due to the contraction tension force at the surface, external work is required to increase the surface area of a liquid.
The surface tension of liquids can be measured directly using a variety of techniques. The most common method is the Wilhelmy plate method, but a rod or ring can also be used. The equipment required for this method can be constructed from basic laboratory components. Sample volumes can range from a few milliliters (e.g., when using a thin rod) to tens or hundreds (or even larger) milliliters. This technique is particularly suitable for measuring the decrease in surface tension when a surfactant is added to the surface and the interfacial tension between two immiscible liquids (e.g., the oil/aqueous solution interface).
Regardless of the technique used, the surface tension of liquids depends on temperature, and this temperature should preferably be controlled or at least recorded. For example, at a temperature close to room temperature, the surface tension of water decreases by 0,152 mN/m with an increase of 1 degree Celsius. Relative humidity has been shown to have an effect on the surface tension of water. A critical factor in the experimental measurement of surface tension is the cleanliness of the equipment and all materials used in sample preparation (e.g., pipettes, syringes, glassware). Even minor contamination of an aqueous sample, especially with an oily chemical, can significantly alter the surface tension due to adsorption of the chemical and its high surface concentration. It is common practice to clean glassware by acid washing followed by a thorough rinsing with high-purity water.
There are two basic methods for measuring contact angle:
Regardless of the method used to measure contact angle, consistency in the sample preparation process is a critical factor. As can be seen from the description of the experimental methods, pore structure and overall porosity affect the contact angle and require control for consistent sample preparation. As long as contact angles are measured on samples that have been compressed to some extent, the compression procedure must be controlled. Surface roughness is another factor that affects the contact angle. Surface roughness can be characterized as the ratio of the actual area of a solid surface to its apparent or projected area.
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